Market Place
Endocrinology, a medicinal
branch that deals with endocrine and metabolic disorders, is witnessing
cutting-edge drug research to develop advanced drugs that can treat
diabetes, obesity, hypoparathyroidism and other
disorders.The endocrinology market is witnessing impressive growth — it is growing at a compound annual growth rate (CAGR) of 7.82 percent. Between 2023 and 2027, the market is poised to increase by US$ 36.5 billion. It includes treatments for various medical conditions, such as type 1 and type 2 diabetes, obesity, hypogonadism (a condition where the body’s sex glands produce little or no hormones), dwarfism, hypo or hyperparathyroidism, acromegaly (abnormal growth of the hands, feet, and face, caused by the overproduction of growth hormone by the pituitary gland) and congenital adrenal hyperplasia (a genetic disorder that affects the adrenal glands).The market is dominated by diabetes treatment drugs — valued at around US$ 48.7 billion in 2018, these are expected to generate US$ 78.3 billion by the end of 2026. The
market for obesity drugs is also expected to reach US$ 50 billion by 2030.The top companies in this
segment include Novo Nordisk, Eli Lilly, Merck, Sanofi, AstraZeneca and Boehringer Ingelheim. Several biotech companies
have joined the race to capture a share of the lucrative market for diabetes
and obesity drugs.Access the Endocrinology Newsmakers Dashboard (Free Excel)Lilly’s Mounjaro, Novo’s Wegovy gear up for larger share of obesity pieIn May 2022, Lilly’s potential blockbuster Mounjaro (tirzepatide) was approved by the US Food and Drug
Administration (FDA) as a once-weekly subcutaneous injection to treat adults with type 2 diabetes. Mounjaro is the first and only dual targeted glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist on the market, and has helped patients achieve a body weight loss of over 20 percent in clinical trials. Novo Nordisk’s Wegovy (semaglutide), the first and only once-weekly GLP-1 receptor agonist approved for weight management in people with obesity, has been found to help patients lose up to 15 percent of their body weight in over 68 weeks. In late 2022, the drug received FDA approval to treat obesity in pediatric patients aged 12 years and older.Last October, FDA granted fast track review designation to Mounjaro as a treatment for obesity. Lilly plans to go to the FDA soon and expects to get approval for the drug this year. Once approved, Mounjaro will give Wegovy a tough fight in the obesity market. Analysts predict Mounjaro to generate around US$ 8.1 billion in annual sales by 2028, while Wegovy is expected to bring in US$ 7 billion by 2030. Meanwhile, Amgen’s AMG 133 is also in early-stage trials for obesity. Access the Endocrinology Newsmakers Dashboard (Free Excel) ‘Skinny shot’ diabetes drugs face supply shortages; Lilly plans to double capacityFollowing its approval in the US in mid-2021, Wegovy quickly became the go-to “skinny shot” drug in Hollywood, thanks to its
impressive weight reduction data. But the drug hit a supply shortage in late 2021 due to manufacturing issues, which the manufacturer managed to fix in the second half of 2022. Novo’s blockbuster type 2 diabetes drug Ozempic is also in limited supply,
but the drugmaker expects the availability to return to normal around
mid-March.The supply constraints of Wegovy and Ozempic, coupled with the craze around using diabetes drugs for weight loss, sparked interest in Lilly’s Mounjaro. But Mounjaro, along with another Lilly drug Trulicity, began facing supply issues last December. While Lilly has fixed Mounjaro’s supply issues for the time being, it plans to double its manufacturing capacity by the year end to avoid any such shortages in the future.Meanwhile, the American Diabetes Association and Mutual Aid Diabetes have sounded an alarm, saying the off-label use of diabetes drugs for weight loss may cause shortages and affect diabetes patients.Access the Endocrinology Newsmakers Dashboard (Free Excel)Provention launches treatment for type 1 diabetes; Novo retains market dominanceIn November, Provention Bio’s Tzield (teplizumab) bagged FDA approval as a preventive treatment for type 1 diabetes in individuals eight years or older who are in stage 2 of the disease. The injectable drug is the first treatment in the US to delay progression of the autoimmune disease.Novo remained the dominant player in the diabetes and obesity market, clocking sales of US$ 22.8 billion (DKK 156.4 billion) in 2022 in this segment. Ozempic’s sales increased by 77 percent to US$ 8.6 billion (DKK 59.8 billion). The Danish company consolidated its position further by
purchasing Dicerna Pharma for US$ 3.3 billion in 2021 for its RNA interference (RNAi) technology.Novo is planning to file for approval of its once-weekly insulin icodec for type 2 diabetes in the US, the EU and China in the first half of 2023. It is also running a phase 1 trial of Ozempic as a once-weekly oral treatment.In 2022, sales of Lilly’s blockbuster drug Trulicity (dulaglutide) touched US$ 7.4 billion. Two other drugs, Humalog and Jardiance, generated US$ 2.1 billion each in sales. In addition, Lilly’s partner Boehringer Ingelheim also reported US$ 2.55 billion (€ 2.5 billion) sales of Jardiance in the first half of 2022.Biosimilar drugmaker Biocon Biologics acquired Viatris’ biosimilars business for a total of US$ 3.34 billion, strengthening its presence in the diabetes, tumors and autoimmune diseases market. Viatris’ portfolio is expected to generate sales of over US$ 1 billion for Biocon in 2023.Access the Endocrinology Newsmakers Dashboard (Free Excel)Drugmakers work on triple agonist therapies to
treat diabetes, obesitySeveral drugmakers are working on triple agonist therapies that target multiple receptors, such as GLP-1, GIP and glucagon (GCG). These drugs, such as Novo and partner Marcadia’s MAR423, Hanmi’s HM1521, Sanofi’s SAR441255, and Eli Lilly’s retatrutide, are currently in early- to mid-stage trials. Studies have shown that these triple agonists are more effective in reducing body
weight and improving glucose control compared to mono- or
dual-incretin receptor agonists.In addition, a few triple drug combinations containing metformin, DPP4 inhibitors and SGLT2 inhibitors have recently been approved. Treatments such as Astra’s Qternmet XR and Lilly-BI’s Trijardy XR have shown
significant improvement in glycemic control and are generally well tolerated by
patients.Access the Endocrinology Newsmakers Dashboard (Free Excel)TheracosBio’s oral med for diabetes approved; gene therapies gather interest Recently, TheracosBio’s Brenzavvy was approved by the agency as an oral
medication for type 2 diabetes. And Marinus Pharmaceuticals’ oral testosterone replacement therapy Kyzatrex received FDA’s nod last year for a range of diseases in men that arise from deficiency or absence of endogenous testosterone. New York-based Oramed is currently conducting a phase 1 trial of its oral GLP-1 drug – ORMD-0901 – as a treatment for type 2 diabetes.Meanwhile, Vertex and Arbor Biotechnologies are working on a gene therapy
(VX-880) for type 1 diabetes. BridgeBio Pharma’s BBP-631 adeno-associated virus (AAV) gene therapy for congenital adrenal
hyperplasia is in phase 1/2 trials. And
Swedish biotech Diamyd is carrying out phase 3 trials of its type 1 diabetes vaccine.In other medical conditions, Ascendis Pharma’s TransCon PTH, a long-acting prodrug of parathyroid hormone, has a PDUFA date in April
2023. If approved, it would become the first hormone replacement therapy to
address the underlying cause of hypoparathyroidism. Crinetics Pharmaceuticals’ Paltusotine, a non-peptide
somatostatin type 2 (SST2) receptor agonist, is currently in phase 3 trials for
acromegaly, representing a new class of oral once-daily medication.Access the Endocrinology Newsmakers Dashboard (Free Excel)Our viewDiabetes and obesity have
reached epidemic proportions in the recent decades, while other endocrine
disorders such as hypoparathyroidism are also growing rapidly the world over.According to the World Health Organization, around 422 million people worldwide have diabetes, and 1.5 million deaths are directly attributed to diabetes each year.While factors
such as long working hours, sedentary lifestyles, and unhealthy eating and
drinking habits are contributing to the rise of these diseases, drugmakers are
doing some cutting edge research for these conditions. Given this scenario,
endocrinology should see a lot of pathbreaking drugs in the coming years.
Impressions: 2095
https://www.pharmacompass.com/radio-compass-blog/endocrinology-newsmakers-drugmakers-work-on-triple-agonist-treatments-oral-insulin-to-fight-diabetes
#PharmaFlow by PHARMACOMPASS
02 Mar 2023
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In 2022, the world finally began to emerge out of Covid-related
restrictions. Though 2020 and 2021 saw several travel-related curbs, there was
no let up in the speed at which generic active pharmaceutical ingredient (API)
manufacturers were submitting Drug Master Files (DMFs) to the US Food and Drug
Administration (FDA). In the four years between 2018 and 2021, the number of
Type II DMF submissions (i.e. submissions for drug substance, drug substance
intermediate, and material used in their preparation, or drug product) remained
steady at over 630 per year.In 2022, the DMF submissions rose at an impressive pace of 12.1
percent. A total of 1,024 DMFs (Types II, III, IV and V) were submitted in
2022, as opposed to 913 in 2021.Last year, Type II DMF submissions increased by 7.2 percent — a total of 715 Type II DMFs were submitted in 2022 as opposed to 667 in 2021. However, of the 715 DMFs filed with the FDA, only 190 (26 percent) had their reviews completed.View FDA DMF Filings in 2022 (Power BI Dashboard, Free Excel Available) DMF submissions from India dip 10.6%, China’s filings increase 45%As always, DMFs filed from India and China were significantly higher than DMFs from other countries. However, the year saw DMF submissions from India drop by 10.6 percent. Overall DMF submission from India stood at 336, as opposed to 376 in 2021. In comparison, China’s DMF filings increased by 45 percent to 231 in 2022, as opposed to 159 in 2021. Interestingly, FDA had issued 31 Form 483s in 2022 out of which 15 were issued to Indian drugmakers. Out of 15, seven Form 483s were issued to manufacturing units belonging to four Indian API manufacturers — Lupin, Aurobindo Pharma, Torrent and Biocon Biologics.While DMFs are submissions to FDA that may be used to provide
confidential, detailed information about facilities, processes, or articles
used in the manufacturing, processing, packaging, and storing of human drug
products, a Form 483 is a notification sent by the FDA to a
drugmaker regarding objectionable conditions at a facility. A Form 483 is
issued at the conclusion of an inspection, when an investigator finds
regulatory violations and/or non-compliance of good manufacturing practices. January 2023 saw a spate of Form
483s issued to Indian drugmakers, raising concerns within the pharma
industry.View FDA DMF Filings in 2022 (Power BI Dashboard, Free Excel Available) India’s Metrochem API tops DMF submissionsIndia’s Metrochem API led the list of companies with the highest number of DMF submissions at 19. MSN Labs stood second with 16 submissions.Other top Indian companies were Aurobindo Pharma (15), Biophore India (15), Hetero Group (11) and Cipla (10), followed by two Chinese companies — BrightGene Bio-Medical Technology and Changzhou Pharmaceutical Factory — with 9 submissions each.The maximum number of DMF filings were for elagolix sodium (11), empagliflozin (eight), tofacitinib citrate (six), revefenacin (six), apixaban (five), brivaracetam (five), cannabidiol (five), followed by mirabegron (five) and tafamidis (five).A total of 79 DMFs were filed for the
first time for 64 products, of which 28 had their GDUFA (Generic Drug User Fee Amendments) review
completed. These
include revefenacin (six), migalastat hydrochloride (three), cupric sulfate (three), ivosidenib (two), upadacitinib (one) and voxelotor (one). Revefenacin is losing
its marketing exclusivity this year.View FDA DMF Filings in 2022 (Power BI Dashboard, Free Excel Available) Our viewIn our last (H1 2022) review of DMF submissions, we had mentioned that less than half of the 350 Type II DMFs filed by the FDA had been reviewed, as the user fee program had not been reauthorized.FDA published the New GDUFA III fee structure at the eleventh hour — on September 30, 2022. GDUFA III includes several enhancements to the abbreviated new drug
application (ANDA) assessment process to maximize the efficiency and utility of
each assessment cycle. These enhancements aim to reduce the number of
assessment cycles and facilitate timely access to safe, effective, high-quality
and affordable generics.With the GDUFA III, the US government has made clear its intent to
lower generic drug prices. In future, more drugs are likely to go off-patent and we are likely to see the number of
DMF submissions rise even further.In
the second quarter of 2022, FDA resumed unannounced inspections in India. The regulator has also stepped up onsite inspections. FDA wants cheaper drugs, but not at the cost of quality. There are no short-cuts for generic and bulk drug manufacturers wanting to export to the US.(This article has been updated to accurately reflect the information on Metrochem API and MSN Labs.)
Impressions: 2212
https://www.pharmacompass.com/radio-compass-blog/dmf-submissions-rise-12-1-in-2022-india-sees-10-6-drop-in-type-ii-filings
#PharmaFlow by PHARMACOMPASS
02 Feb 2023
Acquisitions and spin-offs dominated headlines in 2019 and the tone was set very early with Bristol-Myers Squibb acquiring
New Jersey-based cancer drug company Celgene in a US$ 74 billion deal announced on
January 3, 2019. After factoring
in debt, the deal value ballooned to about US$ 95 billion, which according
to data compiled by Refinitiv, made it the largest healthcare deal on
record.
In the summer, AbbVie Inc,
which sells the world’s best-selling drug Humira, announced its acquisition of Allergan Plc, known for Botox and other cosmetic
treatments, for US$ 63 billion. While the companies are still awaiting
regulatory approval for their deal, with US$ 49 billion in combined 2019
revenues, the merged entity would rank amongst the biggest in the industry.
View Our Interactive Dashboard on Top drugs by sales in 2019 (Free Excel Available)
The big five by pharmaceutical sales — Pfizer,
Roche, J&J, Novartis and Merck
Pfizer
continued
to lead companies by pharmaceutical sales by reporting annual 2019 revenues of
US$ 51.8 billion, a decrease of US$ 1.9 billion, or 4 percent, compared to
2018. The decline was primarily attributed to the loss of exclusivity of Lyrica in 2019,
which witnessed its sales drop from US$ 5 billion in 2018 to US$ 3.3 billion in
2019.
In 2018, Pfizer’s then incoming CEO Albert Bourla had mentioned that the company did not see the need for any large-scale M&A activity as Pfizer had “the best pipeline” in its history, which needed the company to focus on deploying its capital to keep its pipeline flowing and execute on its drug launches.
Bourla stayed true to his word and barring the acquisition of Array Biopharma for US$ 11.4 billion and a spin-off to merge Upjohn, Pfizer’s off-patent branded and generic established medicines business with
Mylan, there weren’t any other big ticket deals which were announced.
The
Upjohn-Mylan merged entity will be called Viatris and is expected to have 2020
revenues between US$ 19 and US$ 20 billion
and could outpace Teva to
become the largest generic company in the world, in term of revenues.
Novartis, which had
followed Pfizer with the second largest revenues in the pharmaceutical industry
in 2018, reported its first full year earnings after spinning off its Alcon eye
care devices business division that
had US$ 7.15 billion in 2018 sales.
In 2019,
Novartis slipped two spots in the ranking after reporting total sales of US$
47.4 billion and its CEO Vas Narasimhan continued his deal-making spree by buying New
Jersey-headquartered The Medicines Company (MedCo) for US$ 9.7
billion to acquire a late-stage cholesterol-lowering
therapy named inclisiran.
As Takeda Pharmaceutical Co was
busy in 2019 on working to reduce its debt burden incurred due to its US$ 62
billion purchase of Shire Plc, which was announced in 2018, Novartis also purchased
the eye-disease medicine, Xiidra, from the Japanese drugmaker for US$ 5.3 billion.
Novartis’ management also spent a considerable part of 2019 dealing with data-integrity concerns which emerged from its 2018 buyout of AveXis, the
gene-therapy maker Novartis had acquired for US$ 8.7 billion.
The deal gave Novartis rights to Zolgensma,
a novel treatment intended for children less than two years of age with the
most severe form of spinal muscular atrophy (SMA). Priced at US$ 2.1 million,
Zolgensma is currently the world’s most expensive drug.
However,
in a shocking announcement, a month after approving the drug, the US Food and
Drug Administration (FDA) issued a press release on
data accuracy issues as the agency was informed by AveXis that
its personnel had manipulated data which
the FDA used to evaluate product comparability and nonclinical (animal)
pharmacology as part of the biologics license application (BLA), which was
submitted and reviewed by the FDA.
With US$
50.0 billion (CHF 48.5 billion) in annual pharmaceutical sales, Swiss drugmaker
Roche came in at number two position in 2019
as its sales grew 11 percent driven by
its multiple sclerosis medicine Ocrevus, haemophilia drug Hemlibra and cancer medicines Tecentriq and Perjeta.
Roche’s newly introduced medicines generated US$ 5.53 billion (CHF 5.4 billion) in growth, helping offset the impact of the competition from biosimilars for its three best-selling drugs MabThera/Rituxan, Herceptin and Avastin.
In late 2019, after months of increased
antitrust scrutiny, Roche completed
its US$ 5.1 billion acquisition of Spark Therapeutics to strengthen its presence in
gene therapy.
Last year, J&J reported almost flat worldwide sales of US$ 82.1 billion. J&J’s pharmaceutical division generated US$ 42.20 billion and its medical devices and consumer health divisions brought in US$ 25.96 billion and US$ 13.89 billion respectively.
Since J&J’s consumer health division sells analgesics, digestive health along with beauty and oral care products, the US$ 5.43 billion in consumer health sales from over-the-counter drugs and women’s health products was only used in our assessment of J&J’s total pharmaceutical revenues. With combined pharmaceutical sales of US$ 47.63 billion, J&J made it to number three on our list.
While the sales of products like Stelara, Darzalex, Imbruvica, Invega Sustenna drove J&J’s pharmaceutical business to grow by 4 percent over 2018, the firm had to contend with generic competition against key revenue contributors Remicade and Zytiga.
US-headquartered Merck, which is known as
MSD (short for Merck Sharp & Dohme) outside the United States and
Canada, is set to significantly move up the rankings next year fueled by its
cancer drug Keytruda, which witnessed a 55
percent increase in sales to US$ 11.1 billion.
Merck reported total revenues of US$ 41.75 billion and also
announced it will spin off its women’s health drugs,
biosimilar drugs and older products to create a new pharmaceutical
company with US$ 6.5 billion in annual revenues.
The firm had anticipated 2020 sales between US$ 48.8 billion and US$ 50.3 billion however this week it announced that the coronavirus pandemic will reduce 2020 sales by more than $2 billion.
View Our Interactive Dashboard on Top drugs by sales in 2019 (Free Excel Available)
Humira holds on to remain world’s best-selling drug
AbbVie’s acquisition of Allergan comes as the firm faces the expiration of patent protection for Humira, which brought in a staggering US$ 19.2 billion in sales last year for
the company. AbbVie has failed to successfully acquire or develop a major new
product to replace the sales generated by its flagship drug.
In 2019, Humira’s US revenues increased 8.6 percent to US$ 14.86 billion while internationally, due
to biosimilar competition, the sales dropped 31.1 percent to US$ 4.30 billion.
Bristol Myers Squibb’s Eliquis, which is also marketed by Pfizer, maintained its number two position
and posted total sales of US$ 12.1 billion, a 23 percent increase over 2018.
While Bristol Myers Squibb’s immunotherapy treatment Opdivo, sold in partnership with Ono in Japan, saw sales increase from US$ 7.57 billion to US$ 8.0 billion, the growth paled in comparison to the US$ 3.9
billion revenue increase of Opdivo’s key immunotherapy competitor Merck’s Keytruda.
Keytruda took the number three spot in drug sales that
previously belonged to Celgene’s Revlimid, which witnessed a sales decline from US$ 9.69 billion to US$ 9.4 billion.
Cancer treatment Imbruvica, which is marketed
by J&J and AbbVie, witnessed a 30 percent increase in sales. With US$ 8.1
billion in 2019 revenues, it took the number five position.
View Our Interactive Dashboard on Top drugs by sales in 2019 (Free Excel Available)
Vaccines – Covid-19 turns competitors into partners
This year has been dominated by the single biggest health emergency in years — the novel coronavirus (Covid-19) pandemic. As drugs continue to fail to meet expectations, vaccine development has received a lot of attention.
GSK reported the highest vaccine sales of all drugmakers with
total sales of US$ 8.4 billion (GBP 7.16 billion), a significant portion of its
total sales of US$ 41.8 billion (GBP 33.754 billion).
US-based Merck’s vaccine division also reported a significant increase in sales to US$ 8.0 billion and in 2019 received FDA and EU approval to market its Ebola vaccine Ervebo.
This is the first FDA-authorized vaccine against the deadly virus which causes
hemorrhagic fever and spreads from person to person through direct contact with
body fluids.
Pfizer and Sanofi also reported an increase in their vaccine sales to US$ 6.4
billion and US$ 6.2 billion respectively and the Covid-19 pandemic has recently
pushed drugmakers to move faster than ever before and has also converted
competitors into partners.
In a rare move, drug behemoths — Sanofi and GlaxoSmithKline (GSK) —joined hands to develop a vaccine for the novel coronavirus.
The two companies plan to start human trials
in the second half of this year, and if things go right, they will file
for potential approvals by the second half of 2021.
View Our Interactive Dashboard on Top drugs by sales in 2019 (Free Excel Available)
Our view
Covid-19 has brought the world economy to a grinding halt and shifted the global attention to the pharmaceutical industry’s capability to deliver solutions to address this pandemic.
Our compilation shows that vaccines and drugs
for infectious diseases currently form a tiny fraction of the total sales of
pharmaceutical companies and few drugs against infectious diseases rank high on
the sales list.
This could well explain the limited range of
options currently available to fight Covid-19. With the pandemic currently infecting
over 3 million people spread across more than 200 countries, we can safely
conclude that the scenario in 2020 will change substantially. And so should our
compilation of top drugs for the year.
View Our Interactive Dashboard on Top drugs by sales in 2019 (Free Excel Available)
Impressions: 54752
https://www.pharmacompass.com/radio-compass-blog/top-drugs-and-pharmaceutical-companies-of-2019-by-revenues
#PharmaFlow by PHARMACOMPASS
29 Apr 2020
This week in Phispers, we bring you news on J&J’s Invokana, a drug that reduces heart risk while increasing the risk of amputation of toes. There is news from Google, which is tying up with India’s Aravind Eye Care System for its artificial intelligence eye doctor initiative. And WHO takes a step towards reducing antibiotic resistance by grouping antibiotics into ‘Access’, ‘Watch’ and ‘Reserve’.
Manufacturing errors trigger drug recalls by Lupin and Dr. Reddy’s in the US
Earlier this month,
we carried an article on the end of India’s pharma honeymoon.
News this week from Lupin and Cipla added another dimension to the problem as manufacturing
errors triggered drug recalls in the United States.
Lupin voluntarily recalled a lot of its birth control pills — Mibelas 24 Fe — in the US. A market complaint indicated a packaging error, making the lot number and expiration
date no longer visible. This product is an oral contraceptive for women.
As a result of the
packaging error, the FDA says the first four days of the birth control packet have four
non-hormonal placebo tablets as opposed to the active tablets. This may place
the user at risk for contraceptive failure and unintended pregnancy.
Similarly, Dr. Reddy’s had to recall hundreds of thousands of cartons of a popular acne medicine — Zenatane — manufactured by Cipla’s plant in Pune.
According to FDA enforcement reports, Dr. Reddy’s is recalling 190 lots, consisting of 778,279 cartons of its Zenatane brand isotretinoin capsules, in four dose sizes. The voluntary Class II recall was initiated in late May after the products failed dissolution testing.
During this period of
turmoil, the Indian company which is generating a lot of positive press is Cadila Healthcare.
Cadila’s US
division Zydus Pharmaceuticals’ subsidiary Nesher Pharmaceuticals has received final FDA approval to
market Nystatin Topical Powder, an anti-fungal
antibiotic used to treat skin infections caused by yeast.
There is more good
news from Zydus Cadila. After years of patent battles, the FDA has approved Zydus Cadila’s generic version
of Shire’s ulcerative colitis drug Lialda.
This came as a rude
shock to Shire investors who had believed the US$ 800 million drug was safe for
a few more years. However, there is a chance that instead of a flood of
generics, the Zydus' generic may be the only competition for Lialda for sometime.
Zydus Cadilla has indicated that its version will have a six-month exclusivity.
J&J’s diabetes
drug saves heart at the cost of toes; Sanofi’s insulin slashes hypoglycemia risks for seniors
Would you like to
sacrifice your toes to save yourself from a heart attack? Well, a diabetes drug
made by Johnson & Johnson (J&J), does just that. The drug — Invokana — decreases the risk of heart attacks and strokes, while increasing the risk of amputation,
particularly of toes.
According to the
results of the 10,142-patient study, funded by J&J, for every three heart
attacks, strokes, or cardiovascular deaths prevented by Invokana, there were
two amputations, 71 percent of them of toes or the lower foot.
While this is a setback to J&J, its rivals — Eli Lilly and Boehringer Ingelheim — who make a similar drug called Jardiance, may be cheering the findings of this
study, performed on sodium-glucose co-transporter 2 (SGLT2) inhibitors. These
drugs prevent the kidney from absorbing sugar from the blood.
But scientists are not sure why the drugs would prevent cardiovascular disease, and it’s unclear why one of them would lead to amputations. “It justifies the need to test each medicine,” Harlan Krumholz of Yale University said.
Another study
examining an at-risk population of seniors who
had switched to basal insulin found Sanofi’s Toujeo to outdo its peers at cutting the risk of
hypoglycemia in older patients.
During a six-month follow-up, the study found that amongst the ‘at-risk’ seniors, those taking Toujeo were 57 percent less likely to experience hypoglycemia than those who switched to competing insulins—such as Novo Nordisk’s Tresiba and Levemir, and Toujeo’s predecessor, Lantus.
Google ties up
with Indian hospital chain for artificial intelligence eye doctor initiative
Google will soon begin
work on a grand experiment that would use machines to widen access of
healthcare. If successful, this initiative will protect millions of diabetes patients
from an eye disease that leads to blindness.
Last year, researchers at Google had said they had trained image recognition algorithms to detect signs of diabetic retinopathy roughly as accurately as human experts. Left untreated, diabetic retinopathy causes blindness. The software examines photos of a patient’s retina to spot tiny aneurisms that would help detect early stages of the disease.
Google is working
with the Aravind Eye Care System in India, a network of eye hospitals, in order
to integrate this technology.
“This kind of blindness is completely preventable, but because people can’t get screened, half suffer vision loss before they’re detected,” Lily Peng, a product manager with the Google Brain AI research group, said. “One of the promises of this technology is being able to make healthcare more accessible.” There are more than 400 million people worldwide with diabetes, including 70 million in India.
FDA tells Endo to
pull out its opioid pain medication, as Gottlieb attacks addiction
Last week, the US FDA
asked drugmaker Endo Pharmaceuticals to remove its powerful opioid pain medication — Opana ER — from the market, due to “the public health consequences of abuse”.
“We are facing an opioid epidemic — a public health crisis — and we must take all necessary steps to reduce the scope of opioid misuse and abuse,” FDA Commissioner Dr. Scott Gottlieb said. “We will continue to take regulatory steps when we see situations where an opioid product’s risks outweigh its benefits, not only for its intended patient population but also in regard to its potential for misuse and abuse,” he added.
Opioid overdoses killed 33,000
Americans in 2015, with half of those involving a prescription opioid.
Opana ER, which is oxymorphone hydrochloride, is used to manage severe pain. The FDA
approved it for this use in 2006. The drug is about twice as powerful as OxyContin, another often abused opioid.
In 2012, Endo
reformulated the drug to make it more resistant to physical and chemical
tampering. While the drug met the standards for approval, FDA says Endo never
showed that the reformulation would reduce abuse.
Amgen loses bid to delay Novartis’ biosimilar; FDA rejects Coherus’ biosimilar for Neulasta
Amgen lost a case in the Supreme Court of the United States that
sought to delay biosimilars of its rivals. Amgen had argued that its biosimilar rivals
should be forced to delay their 180-day marketing notices until the FDA had
made up its mind on the marketing application.
However, on Monday, the Supreme Court took a decision by determining that the law never imposed a two-tier timing system for these notices. Therefore “the applicant may provide notice either before or after receiving FDA approval.”
This has proven to be
a clear win for Sandoz — the generic unit of Novartis that is fielding an array of copycat biologics. The group is launching a copy of Amgen’s Neupogen. And in the process, Sandoz has
unleashed a fresh wave of biosimilars hitting the US market.
However, Amgen won somewhere else — the FDA rejected Coherus Biosciences’ application for a biosimilar of Amgen’s blockbuster Neulasta (a drug that fights infections in cancer
patients). This action effectively delays any rival until 2018, at the
earliest.
The FDA's response
comes as Amgen gears up for biosimilar competition for Neulasta, which
generated about US$ 4.6 billion in sales last year. The FDA requested Coherus
for a re-analysis of certain data and asked the drug developer for more
manufacturing information.
WHO updates list
of essential medicines; groups antibiotics into three categories
Last week, the World
Health Organization (WHO) released its Essential Medicines List (EML), with a
new advice on which antibiotics to use for common infections and which to
preserve for serious circumstances. Amongst the additions to the WHO Model list of essential medicines
for 2017 are medicines for HIV, hepatitis C, tuberculosis and leukaemia.
The EML is used by
many countries to increase access to medicines. The updated list has added 30
drugs for adults and 25 for children, and specifies new uses for 9
already-listed products. In all, it contains 433 drugs deemed essential to
address the most important public health needs.
This time, WHO has grouped antibiotics into three categories – ACCESS, WATCH and RESERVE – with recommendations on when each category should be used.
Initially, the new
categories apply only to antibiotics used to treat 21 of the most common
general infections. If found useful, it could be broadened in future versions
of the EML to apply to drugs to treat other infections.
Antibiotics in the
ACCESS group must be available at all times as treatments for a wide range of
common infections. It includes drugs like amoxicillin, an antibiotic used to treat infections such as
pneumonia.
The WATCH group
includes antibiotics that are recommended as first- or second-choice treatments
for a small number of infections. For example, the use of ciprofloxacin, used to treat cystitis (a type of
urinary tract infection) and upper respiratory tract infections (such as
bacterial sinusitis and bacterial bronchitis), should be dramatically reduced
to avoid further development of resistance.
The third group, RESERVE, includes antibiotics that should be considered as last resorts, such as colistin and some cephalosporins. These must be used
only in the most severe circumstances when all other alternatives have failed.
Impressions: 3373
https://www.pharmacompass.com/radio-compass-blog/j-j-s-diabetes-drug-reduces-heart-risk-at-the-cost-of-toes-google-s-ai-eye-doctor-initiative
#PharmaFlow by PHARMACOMPASS
15 Jun 2017
This
week, Phispers brings you the latest twist in the Singh brothers-Daiichi 2008
Ranbaxy sell-off saga. There is also news on the benefits of new diabetes and
cholesterol drugs to the heart; amendments to drug regulations in Canada; a
class action suit against Sun and Mylan in the US; and the sale of the
controversial DMD drug by Marathon. Read on.
Singhs fight back; say Daiichi’s profits outweigh losses incurred in buying Ranbaxy
Last
year, a Singapore tribunal had ordered the former promoters of Ranbaxy — Malvinder and Shivinder Singh — to pay Daiichi Sankyo US $ 391 million (Rs
25.62 billion) in damages for concealing information regarding wrongdoings at
Ranbaxy. The Singh brothers had sold their majority stake in Ranbaxy to the
Japanese drug maker in 2008 for US$ 4.6 billion.
Last
week, the Singh brothers hit back at Daiichi. The Singh brothers now claim Daiichi has made
profits that far outweigh the losses it incurred in buying Ranbaxy in 2008.
According to a new application filed in the Delhi High Court,
the Singhs claim Daiichi had availed monetary benefits of around US$ 1.2
billion (Rs 80 billion) during the time it
bought and sold Ranbaxy. This amount is
more than twice the damages Daiichi is seeking through its arbitration
enforcement case against the brothers.
The application further states that such monetary benefits
should have been factored in by the Singapore tribunal in assessing the
damages.
According to this new application, Daiichi made further profits from the sale of its
shares in Ranbaxy to Sun Pharma in 2015.
Singhs have appealed in both the Delhi High Court as well as in Singapore. The brothers claim “substantive
objections” exist under India’s arbitration law to make the order unenforceable.
Data-integrity
violations uncovered at USV in India; more violations at Jinan Jinda in China
USV
Private Limited: Another major Indian pharmaceutical company — 55 year-old USV Private Limited — received an FDA warning letter
after shortcomings were uncovered at its finished pharmaceuticals manufacturing
facility in Dabhel (in Daman) during a June 2016 inspection.
While the FDA questioned the practices at USV’s microbiological laboratory and its way of conducting smoke studies, data integrity violations were yet again cited in the warning letter.
According to the warning letter, at USV “all users could delete or modify files” and investigators uncovered six deleted tests on two different equipment. In another instance, where a sample had “failed identity testing”, USV accepted a passing retest result “without any investigation of the failed result”.
The warning letter goes on to mention that the “FDA cited similar CGMP violations at other facilities in USV’s network.”
In the financial year 2015-16, USV’s total income was US$ 388 million (Rs
25.4 billion). USV’s Indian business contributed 82 percent to the revenue and the rest was from export of APIs and finished dosages.
Jinan
Jinda Pharmaceutical:
The US FDA had placed Jinan Jinda Pharmaceutical Chemistry Company Ltd on its Import Alert list in November 2015. An
inspection conducted six months earlier, by the Italian Ministry of Health, had
uncovered an unofficial and non-controlled storage area that contained mainly
raw materials and finished products, and was made inaccessible to the inspectors.
Since the door of the area had been removed and replaced with a panel fixed
with screws to the wall, the inspection team concluded that there was a serious
risk of data falsification.
A
June 2016 inspection by the FDA
uncovered that when an out of specification (OOS) unknown impurity peak was
found during high performance liquid chromatography (HPLC) testing, the
chemists terminated the analysis. When repeat testing also showed the OOS
impurity peak, the chromatogram was manually edited to hide the presence of the
peak. In another case, where seven sample injections were required to test for
impurities, the analysts permanently deleted the first five sample injections
and then renamed the last two injections and reported that they met
specifications.
With repeated concerns of data-integrity, FDA’s warning letter clearly spells out what is expected from the firm going forward. This includes — “a comprehensive investigation into the extent of the inaccuracies in data records and reporting”; and “a current risk assessment of the potential effects of the observed failures on the quality” of drugs manufactured by Jinan Jinda.
The letter states that Jinan Jinda’s assessment should include “analyses of the risks to patients”. It goes on to add that the company’s management strategy should include the details of the company’s “global corrective action and preventive action plan.”
Drug
makers in Canada to publicly disclose drug shortages
Last week, amendments to Canada’s Food and Drug Regulations came into force, making it mandatory for drug authorization holders to publicly report drug shortages and discontinuations. These will now have to be reported to two websites — DrugShortagesCanada.ca and PenuriesDeMedicamentsCanada.ca.
The public-facing website of Canada — www.drugshortages.ca — said: “As soon as a market authorization holder knows that it will take longer than 20 days to supply a drug to meet expected patient volumes on an ongoing basis, they will report this as a shortage on the communications platform.”
According to Health Canada, the posting of discontinuances on the shortages website “does not alter nor affect regulatory obligations under the Food and Drug Act Regulations to inform Health Canada within 30 days of any drug discontinuances.”
Sun,
Mylan face class action suit in US over price fixing of asthma drug
A class action suit was filed in the Pennsylvania federal court last week by the New York grocery workers’ union against Sun Pharmaceutical Industries
and Mylan. The lawsuit alleged that the two companies conspired to raise the price of a generic asthma medicine — Albuterol, or albuterol sulfate tablets.
Albuterol
is a bronchodilator, used by patients suffering from wheezing.
The suit — filed by the United Food and Commercial Workers local unit — stated that Sun and Mylan had raised their prices for albuterol sulfate over 3,000 per cent between October 2013 and April 2014.
“Beginning in May 2013, defendants caused the price of albuterol sulfate to dramatically increase in unison. The increases were the result of an agreement among them to increase pricing and restrain competition for the sale of albuterol sulfate in the US,” the complaint alleged.
The
New York union also filed another suit for similar charges against Mylan and Sandoz for colluding to raise the cost of another generic asthma medicine — Benazepril HCTZ.
New
age diabetes and cholesterol drugs will also protect your heart
There are new drugs that significantly protect your heart, and reduce the risk of death and hospitalization. Take the case of a newer class of type 2 diabetes drugs — known as SGLT-2 inhibitors — that significantly reduce the risk of death and hospitalization for heart failure as compared to other medicines for diabetes. This was brought out by a study sponsored by AstraZeneca.
SGLT-2 inhibitors work by removing blood sugar via the urine. They are sold under various brand names such as AstraZeneca’s Farxiga,
Eli Lilly and Boehringer Ingelheim’s Jardiance and
Johnson & Johnson’s Invokana.
Similar breakthrough was reached by Amgen through its cardio research that highlighted health benefits of its PCSK9 cholesterol drug — Repatha. This drug was studied by Amgen for two years, across 27,564 patients. “Repatha was able to lower a composite of cardio risks by an average of 20 percent. And the improvement increased with time, growing from a 16 percent risk advantage in year one to 25 percent after 12 months,” a news report said.
In 2015, a clinical trial conducted on Eli Lilly and Boehringer Ingelheim’s Jardiance to reassure it does not cause heart problems instead showed it reduced the combined risk of hospitalization for heart failure or death from heart failure by 39 percent in high risk patients. Since then, this heart benefit has been incorporated in Jardiance’s label.
Meanwhile, AstraZeneca is conducting its own large clinical
trials to determine the heart effect of Farxiga. The results of these trials
are expected in 2019.
After
pricing outrage, Marathon sells DMD drug to PTC Therapeutics
After weeks of public and political outrage over the pricing of its Duchenne muscular dystrophy (DMD) drug — Emflaza — Illinois-based Marathon Pharmaceuticals
said it will sell the drug to PTC Therapeutics.
PTC
Therapeutics will pay US $140 million in cash and stock for
Emflaza. Marathon will also receive payments from the New Jersey-based PTC
on sales of the drug, starting in 2018. DMD is a rare genetic disorder
that causes progressive muscle deterioration and weakness.
On February 9 this year, Marathon received FDA approval for
Emflaza (deflazacort), tablets and oral suspension, to treat patients of DMD,
aged five years and older.
Subsequently, Marathon announced it would charge a list
price of US $ 89,000 a year in the United States for Emflaza. Outside the US,
the drug is available for US $ 1,000 a year.
This led to public outrage, and even the FDA — which had approved Emflaza only in February this year — questioned the drug’s approval. This was the first FDA
approval of any corticosteroid to treat DMD and the first approval of
deflazacort for any use in the US.
Impressions: 2312
https://www.pharmacompass.com/radio-compass-blog/singh-bros-hit-back-at-daiichi-in-ranbaxy-case-new-drug-shortages-legislation-in-canada
#PharmaFlow by PHARMACOMPASS
23 Mar 2017
This week, Phispers brings you news on the probable new head of the US FDA. Meanwhile, pharma biggies like Mylan, Endo, Eli Lilly, AstraZeneca and Sanofi have announced restructuring and layoffs, Switzerland’s Lonza has announced plans to buy Capsugel and Perrigo plans to offload its API plant in India to Strides Shasun. And there is more, read on.
Trump likely to pick venture capitalist Scott Gottlieb to head FDA
America’s President-elect Donald Trump is considering Scott Gottlieb, a partner at one of the world's largest venture
capital funds and a former deputy commissioner at the US Food and Drug
Administration (FDA), to run the government healthcare agency.
News comes days after Jim O’Neill — managing director at Mithril Capital Management, a venture capital firm run by Peter Thiel (the billionaire Trump donor and transition team advisor) — was said to be considered for the FDA top-job.
According to Michael Gaba, federal policy leader of law firm Holland & Knight’s national healthcare
and life sciences team, Gottlieb is a more “palatable” choice, as opposed to O’Neill, who believes that drugs should be allowed on the market before their efficacy has been established, as long as they are safe.
Because if O’Neill heads the FDA, neither the doctor nor the drug maker would have a clue whether the medicine will actually work or not, because the
government never required it to be tested.
Gaba is of the view that the drug industry too is likely to oppose O’Neill’s stance, since companies want to be able to make credible claims about their products, and that they are indeed effective in treating the ailments they claim to treat.
Layoffs at Sanofi, Lilly, Mylan, AstraZeneca and Endo
Over the last week, five pharmaceutical biggies that together account for a market cap of US $ 228 billion in the US bourses — Mylan, Endo Pharmaceuticals, Eli Lilly, AstraZeneca and
Sanofi — have announced major restructuring and layoffs.
The decisions of these companies are driven by a number of factors
ranging from failures in clinical trials to feeling the need to squeeze off
dead weight in the face of wilting sales.
There was some good news for Endo — its Par Pharmaceutical unit launched the first copycat of Merck’s cholestrol-fighting drug Zetia. Endo’s Zetia is
the only copycat for six months under FDA exclusivity rules. Though Merck’s Zetia sales (pegged at US $ 2.5 billion in 2015) is likely to suffer from this copycat drug, the company will face the biggest declines in Zetia sales after that 180-day monopoly ends next year. That’s when multiple generics players are likely to jump in the fray.
For Endo, the Zetia generic presents an opportunity to recoup sales as it struggles to redefine itself. Endo’s generic launch comes just after it cut 375 staffers and pulled the plug on a pain med project. Endo bought Par Pharmaceutical last year for US $ 8 billion. Par will share profits for the generic with its licensing partner — India-based Glenmark Pharmaceuticals.
Eli Lilly also had some good news — in the coming weeks, two leading US medical societies are poised to issue new diabetes treatment guidelines reflecting the lifesaving cardiovascular effects of Eli Lilly's Jardiance. This is likely to push up Jardiance sales.
Swiss drugmaker Lonza in talks to buy Capsugel for around US $ 5 billion
In a statement, Lonza Group AG, the Swiss pharmaceutical manufacturer, said it is in advanced talks with private equity firm KKR & Co LP to acquire
Capsugel, an American manufacturer of capsule products and other drug delivery
systems.
The potential transaction, according to
sources quoted in a Reuters news report, is likely to be valued at more
than US $ 5 billion.
Capsugel “would fit perfectly with Lonza’s ... strategy and strengthen its position as leading supplier to a number of important healthcare markets,” Lonza said in a statement. “A successful acquisition would be value adding and be within Lonza's stated acquisition criteria,” it added.
Under pressure to shore up finances, Perrigo offloads API plant to
Strides
Perrigo is offloading the FDA-approved API plant in Ambernath, Maharashtra, for a consideration
of US $ 14.8 million (INR 1,000 million) to India’s Strides Shasun. Perrigo has been under pressure from investors to shore up its
finances.
On its part, Strides has been shoring up its API business, following its merger with Shasun Pharmaceutical Ltd in 2014. After the acquisition, Strides will continue to produce some of Perrigo’s products at the plant under a long-term agreement. The deal is expected to close by the end of the year.
With this acquisition, Strides will get a plant that had sales of about US $ 10.9 million for the fiscal year ended March 31, 2016. It went through its last FDA inspection without a Form 483.
Strides
intends to use the facility for captive consumption APIs and will move all of
its integrated drug master files (DMFs) for captive consumption to the Perrigo
plant, which has a potential capacity of 600 tons per year. Now, Sweden too wants to host London-based EMA post Brexit vote
After other European Union (EU) members — such as Spain, France and Poland — have shown keenness to become the future location of the London-based European Medicines Agency (EMA), the Swedish government last week launched a campaign to become the new host of the drug agency after Britain’s vote to leave the EU.
The tussle to host the 900-strong EMA is
likely to form a part of complex political horse-trading around Brexit. Italy,
Denmark and Ireland have also put themselves forward as hosts.
“With one of Europe’s top national medicines agencies, an excellent climate for research and life science as well as good conditions for an efficient relocation, Sweden is a good future home for the EMA,” Sweden’s healthcare minister Gabriel Wikstrom said in a statement.
Diabetes drug Pioglitazone may pose risk of bladder cancer, confirms FDA
The US FDA has said it still believes that pioglitazone (sold as Actos and other brands) — the type 2 diabetes drug — may pose an increased risk for bladder cancer
after updating its review of published research.
Research on pioglitazone has gone back and forth on this issue. Back in 2011, the FDA had added a warning about the increased risk for bladder cancer to the drug’s label based on interim results of a 10-year epidemiological study of patients with diabetes in the database of
Kaiser Permanente (KP) of Northern California.
The data suggested that bladder cancer risk rose as the dose and
treatment duration increased. The revised label advises clinicians not to
prescribe pioglitazone for patients with active bladder cancer and to exercise
caution while using it in patients with a history of the cancer.
Subsequent studies (one in 2014, another in 2015) rebutted the causal
link between pioglitazone and bladder cancer. The 2015 study, published in the Journal
of the American Medical Association, looked at the full 10 years of data
drawn from the KP database but could no longer find the cancer signal detected
in the interim results.
However, a retrospective cohort study published earlier this year reported a 63
percent higher risk for bladder cancer for pioglitazone, with longer duration
and larger doses increasing the risk.
Impressions: 2500
https://www.pharmacompass.com/radio-compass-blog/venture-capitalist-likely-to-head-usfda-layoffs-at-sanofi-lilly-mylan-astrazeneca-and-endo
#PharmaFlow by PHARMACOMPASS
15 Dec 2016
This week, Phispers reports on Sanofi and Boehringer Ingelheim’s asset swap, a possible cure for Alzheimer’s disease, a diabetes drug that may soon carry a claim on how it cuts the risk of heart diseases and a lot more. EU and US
regulators compete on rigor during inspections It seems that the European and the American regulators have been trying to outdo one another in terms of proving the
rigor in
their inspections. When it comes to European Medicines Agency (EMA), three of
the seven non-compliance reports Eudra GMP posted in the last one month
addressed sites in the US, while the remaining four were located in India. Similarly,
the US Food and Drug Administration (FDA) imposed an import alert against a Teva
Pharmaceuticals site in Hungary and issued warning letters to BBT Biotech in Germany and
Corden Pharma in Italy during the last one month. On June 21, FDA also issued an import alert for a site in the UK. “Perhaps this is the beginning of a my-inspectors-are-more-rigorous-than-yours type of unofficial competition…,” says a report on the
Unger Consulting website. Sanofi and
Boehringer Ingelheim confirm asset swap Earlier
this week, Sanofi and
Boehringer Ingelheim announced they have signed contracts that secure the strategic transaction initiated by the two companies in December 2015 – that of an asset swap. Under the agreement, Sanofi’s animal health business – Merial – and Boehringer Ingelheim’s
consumer healthcare (CHC) business will be exchanged by the two companies. This
step marks a major milestone before closing of the transaction, which is
expected by 2016-end. However, the swap remains subject to approval by all
regulatory authorities in different territories. Upon closing, this transaction
will be a significant business swap in the pharma sector and an important event
in the history of both companies. Does Eli Lilly have the cure for Alzheimer’s?Eli Lilly has begun
human tests using an entirely new approach to finding a cure to Alzheimer’s disease. Under the new approach, the company targets an aberrant protein called tau that spreads through the brain as Alzheimer’s progresses, “accumulating in telltale tangles that strangle brain cells,” says a Bloomberg news report. Lilly’s tau drug marks a shift in Alzheimer’s research. Previously, Lilly had spent nearly three decades working on drugs for Alzheimer’s, focusing on a different protein called amyloid that was assumed to trigger the disease. In fact, drug companies have spent billions of dollars on amyloid-blocking drugs. At least 190 Alzheimer’s drugs have failed in human trials, according to Bernard Munos, a senior fellow at FasterCures, a think tank that focuses on accelerating medical research. Former
commissioners demand independence for the FDASix
former FDA commissioners who led the American regulator for a total of 32 years
met recently and called for independence and elevation of the FDA’s status. According to them, making the FDA a Cabinet-level organization
or finding another way to give it more autonomy would be a step in the right
direction for public health. The FDA is currently part of the Department of Health and Human Services (HHS). Dr. David Kessler, who headed the FDA from 1990 to 1997, pointed out that there are 150 people between the FDA commissioner and the President of the US. “They all think they’re your boss, and that’s the problem,” Kessler said at the Aspen Ideas Festival. Former FDA commissioners expressed frustration that decisions had been made at levels above the FDA that were not supported by science and ran contrary to what the FDA’s staff had concluded. Dr. Reddy’s terminates tie-up with GSKIndia’s second largest drug maker – Dr. Reddy’s Laboratories – has terminated a
strategic alliance with GlaxoSmithKline (GSK) for emerging markets outside India and plans to pursue these markets on its own. “As part of our company strategy and in light of our strong portfolio of products, we have decided to expand into select new markets,” Dr. Reddy’s said in its annual report filed on Friday with the Securities and Exchange Commission (SEC). “To supplement our own entry and growth in these markets, we have reached an agreement with GSK to take back the marketing rights for key products in these markets. To enable this, both the parties have agreed to terminate the old agreement,” Dr. Reddy’s said. Earlier
this year, Sun Pharma and US drug
maker Merck terminated their branded generics joint venture. The deal was signed between Sun Pharma and Merck in 2011 to develop innovative, branded generics for emerging markets. Report seeks clarification from FDA on
real-world evidence to support clinical trialsLast week, Bipartisan Policy Centre – a non-profit organization – released a new report that calls for the FDA to clarify ways in which real-world evidence can be used to support clinical trials and
post market commitments. The 32-page report offers a number of
rehashed arguments that try to place at least part of the blame for the slow
drug and device development process on the FDA and the regulatory pathways by
which drugs and devices are approved. Arizona runs
out of lethal drugs used for executionsThe
American state of Arizona has run out of
execution drugs, including a sedative – midazolam – implicated in botched lethal injections, according to a filing in a court case that challenges Arizona’s execution methods.Last
month, Pfizer had said it has banned the sale of execution drugs, including midazolam. This move cut off the last major US source for drugs in the deadly mixes. “What is more, the Department's source of midazolam has vanished under pressure from death penalty opponents,” the court document said. A
lawsuit was filed on behalf of seven death-row inmates who allege that
Arizona's use of midazolam and two other drugs violate the US Constitution's
ban on cruel and unusual punishment. According to the Death Penalty Information
Center, the number of inmates executed in the US has dropped sharply since the
1990s, with 14 executions so far this year. Diabetes drug
Jardiance may soon carry claims related to heart diseasesNext week, an FDA advisory panel will be asked to vote on whether a diabetes drug – Jardiance, also known as empagliflozin – made by Eli Lilly and Boehringer Ingelheim cuts the risk
of cardiovascular death. The advisors will recommend whether empagliflozin should include
a claim that it cuts the risk of heart problems in patients at high risk.
Though the FDA is not obliged to follow the advice of its advisory panels, it
generally does follow it. In
2014, the FDA had approved Jardiance as a drug that helps lower blood sugar in
patients with type 2 diabetes. But it also asked companies to conduct an
additional clinical trial to show it did not increase the risk of heart
problems. When the companies submitted their results, it showed the drug
actually cut the risk of death from heart attacks and strokes, becoming the
first glucose-lowering drug to show protective results in a large clinical
trial.
Impressions: 2670
https://www.pharmacompass.com/radio-compass-blog/us-and-eu-compete-on-regulatory-vigor-former-chiefs-seek-elevation-of-status-for-fda
#PharmaFlow by PHARMACOMPASS
30 Jun 2016
This week, the
biggest news in the world of pharmaceuticals was the termination of the Pfizer-Allergan mega-merger due to new measures taken by the US government. Post that, Allergan signed a US $ 3 billion licensing deal with UK’s Heptares for a portfolio of neurological drugs. But a lot more happened last week – for instance, Pfizer and Celltrion won approval for a biosimilar of J&J’s Remicade, GSK said it wants to make it easier for manufacturers in least-developed
countries to make its drugs and Valeant terminated the salesforce for its female libido pill. Pharmaceutical
Whispers (Phispers) brings you the latest news from across the world. Pfizer-Allergan terminate
merger; Allergan signs licensing deal with HeptaresOn Monday, the US Treasury announced new measures to curb tax-inversion deals. The measures seemed to specifically target the Pfizer-Allergan US $ 160 billion mega deal. And, by Wednesday, the US government had achieved its desired objective – Pfizer and Allergan announced their decision to mutually terminate
the deal. Allergan, which is run from New Jersey but has a legal
domicile in Dublin, last year agreed to merge with Pfizer. This mega-merger
would have moved the Pfizer headquarters from New York to Dublin, saving the
pharma behemoth billions of dollars in taxes. As per news reports, Pfizer will need to pay a US $ 400
million fee to Allergan for expenses relating to the deal. Though the US
Treasury decision and the termination of the Pfizer-Allergan deal represents a
victory for President Barack Obama, whose administration proposed tougher rules
aimed at curbing tax inversions, Allergan is not wasting time. Just hours after Allergan backed away from the US $ 160
billion-merger with Pfizer, the company bounced back with a US $ 3.3 billion licensing deal for global
rights to a portfolio of drugs for neurological disorders from the UK's
Heptares. The deal sends a clear signal that Allergan CEO Brent Saunders plans
to barrel ahead with new pacts to bolster the company's pipeline. Pfizer, Celltrion win approval for biosimilar of J&J’s RemicadeNot all news this week was negative for Pfizer as the FDA approved Celltrion’s biosimilar application of Johnson & Johnson’s Remicade.
The product will be co-marketed by Pfizer in the United States, a relationship
Pfizer accessed through its acquisition of Hospira last
year. Celltrion’s application is only the second biosimilar approved by the FDA. However, unlike generic medicines, biosimilars which have been currently approved are not interchangeable with the reference drug. The European Medicines Agency also issued
a positive opinion to the Bioepis copy of Remicade. Samsung Bioepis, a joint
venture between a unit of the Samsung group and Biogen, has
become a force in the biosimilar drugs industry. In fact, South Korea too is
emerging as a hub for biosimilar production. Last week, Bioepis filed a lawsuit
against AbbVie Inc., makers of the world’s best-selling rheumatoid arthritis drug – Humira – which generated sales of US $ 14 billion last year. In 2015, Johnson & Johnson’s Remicade sales
were US $ 6.5 billion. Glaxo not to patent drugs
in poorer countriesIn an unusual step, GlaxoSmithKline said it wants to make it
easier for manufacturers in the world's 48
least-developed countries to copy its medicines. The company said it would not
file patents in these countries in the hope that by removing the fear of
patent litigation and by allowing independent companies to make and sell
versions of its drugs in those areas, it would widen
public access to these drugs. In countries classified as lower middle income countries by GSK, it will continue to file patents, but will grant licenses to generic manufacturers in exchange for a “small royalty”. Gilead
has adopted a similar model, of granting
generic licensing agreements in developing countries, for
its blockbuster Hepatitis C treatment, Sovaldi. The end of the female
Viagra?Valeant Pharmaceutical, still reeling from all its
accounting and price-gouging problems, has terminated
the sales force for the female libido pill that it acquired last year for US
$ 1 billion. The drug – Addyi (flibanserin) – failed to gain traction in its first six months on the market. Valeant’s stock has plunged 90 percent since its peak in August last year. Valeant plans to relaunch its sales effort for Addyi with an internal team it will build in the coming months, says a Bloomberg news report. In the meantime, the drug will still be available. Along with the 140 contract workers that make up the Addyi sales force, Valeant is firing about 140 employees across its dermatology, gastrointestinal and women’s health divisions, with dermatology taking the biggest hit. Valeant has about 22,000 employees. Alkem, Rusan and Anuh Pharma – data-integrity issues raise its ugly head yet again in India
Inspection at Alkem: In July 2015,
the European Union banned the marketing of around 700 generic medicines for alleged
manipulation of clinical trials conducted by India's pharmaceutical
research company GVK Biosciences. And this year, another laboratory is under
the lens of EU regulators.A routine inspection by the European Medicines Agency in
March 2015 of the Department of Bioequivalence of Alkem Laboratories,
a major generic drugs manufacturer in India, raised
concerns regarding study data used to support the marketing authorization
applications of some drugs in the EU. Rusan Pharma back in
news: In an inspection conducted in 2010 at Rusan Pharma’s facility in Gandhidham (India), the UK’s Medicines and Healthcare Regulatory Agency (MHRA) uncovered “evidence of fraudulent presentation of data” and determined that the site did not comply with Good Manufacturing Practices (GMPs). The same year, another unit of Rusan, located in Ankleshwar (India), did not meet GMP compliance standards during an inspection conducted by Romania’s National Agency for Medicines and Medical Devices. This week, Rusan was back in news. In January 2016, re-inspection by UK’s MHRA of the Gandhidham site found the Pharmaceutical Quality System “not operating in an adequate manner”. In addition, the inspection report mentions “there was not adequate evidence that the root causes of critical data integrity issues raised at the last inspection had been addressed.” Non-compliant
sourcing of drugs by Anuh Pharma: The French Health Agency’s inspection at Anuh Pharma’s
facility in Boisar (India) revealed the firm was sourcing commonly used Azithromycin
from a non-EU GMP compliant source (Hebei
Dongfeng Pharmaceutical Company Limited, China), micronizing the product and then directly exporting it to Europe under the manufacturer name, Anuh Pharma. In addition, several documents were found within a pile of
rubble which included an original batch repacking record. A large number of
active substances were manufactured at the site, such as chloramphenicol,
chloramphenicol
palmitate, erythromycin,
erythromycin
ethylsuccinate, roxithromycin,
ciprofloxacin
HCl etc. Catalent’s compliance problems delay OPKO’s new drug launchWith more than 40 manufacturing facilities around the
world, Catalent
is a preferred manufacturing partner for several major pharmaceutical companies
across the world. OPKO Health,
Inc., one of Catalent’s customers submitted its application for RAYALDEE® (calcifediol)
to the FDA. In the complete response letter (CRL) issued to the company, the
FDA indicated observations of
deficiencies at Catalent’s St. Petersberg, Florida, facility as a result of an FDA field inspection initiated on March 14, 2016, and had held up the new drug approval. According
to a news
report, OPKO revealed the deficiencies occurred at Catalent’s primary softgel development and manufacturing at St Petersburg, Florida, which was hit with a Form 483 being issued on March 25. Meanwhile,
Catalent began production of essential drugs at its French
plant, which had been suspended by France’s health regulator in November last year due to occurrence of out-of-place capsules in several product batches. Safety warnings for
new age diabetes drugs -- saxagliptin and alogliptin Last
year, the FDA had issued safety warnings on new age diabetes drugs called SLGT2
inhibitors (canagliflozin, dapagliflozin, and empagliflozin) and PharmaCompass
had asked the question, “Diabetes: Which new drug is the safest?”. At
the time Merck succeeded in demonstrating
the cardiovascular safety of Januvia®, which was not the case for other
products in the same categrory such as AstraZeneca’s Onglyza® (saxagliptin) and Takeda’s Nesina® (alogliptin). This
week the FDA issued a
safety warning on Onglyza® (saxagliptin) and Nesina® (alogliptin) as the
evaluation of two clinical trials determined that more patients
who received saxagliptin or alogliptin-containing medicines were hospitalized
for heart failure compared to patients who received an inactive treatment
called a placebo. Blockbuster drug
approval expected soon for non-alcoholic fatty liver The FDA reviewed the application of Intercept Pharmaceuticals Inc's liver drug, Obeticholic Acid (OCA) and did not raise any major red flags indicating a high
likelihood that it will get approved. While the drug is being reviewed for use in patients with
primary biliary cirrhosis, a rare liver disease, late-stage studies are
underway on the same drug to treat non-alcoholic steatohepatitis (NASH), which
has no approved treatment. Obeticholic acid (OCA) is listed as one of the top 10
possible blockbuster drugs by FierceBiotech with an expected
sales in 2020 of US $ 1.6 billion. Gilead is also actively building its liver disease pipeline
and this week, the company paid
US $ 400 million upfront to acquire an early-stage pipeline of liver
disease drugs from privately held Nimbus Therapeutics. Heart-disease science
turns over its headScience is supposed to be simple – for instance, LDL is bad cholesterol and HDL is good cholesterol. If a drug lowers the bad cholesterol and increases the good
one, the risk of heart disease should reduce significantly. Specialists were stunned by the results of a study
of 12,000 patients, announced on Sunday at the American College of Cardiology’s annual meeting: “There was no benefit from taking the drug, Evacetrapib.” The drug’s maker, Eli Lilly,
stopped
the study in October, citing futility, but it was not until Sunday’s meeting that cardiologists first saw the data behind that decision. As per the study, participants taking the drug saw their LDL
levels fall to an average of 55 milligrams per deciliter from 84. Their HDL
levels rose to an average of 104 mg per deciliter from 46. Yet 256 participants had heart attacks, compared with 255
patients in the group who were taking a placebo. Ninety-two patients taking the
drug had a stroke, compared with 95 in the placebo group. And 434 people taking
the drug died from cardiovascular disease, such as a heart attack or a stroke,
compared with 444 participants who were taking a placebo.
Impressions: 2997
https://www.pharmacompass.com/radio-compass-blog/phispers-pfizer-allergan-end-megamerger-gsk-wants-to-make-copying-its-drugs-easier-more
#PharmaFlow by PHARMACOMPASS
07 Apr 2016
Each year,
the US Food and Drug Administration (FDA) approve hundreds
of new medications. A small subset of approvals, classified as novel drugs, are considered to
be truly innovative products that often help advance clinical care.
In 2015, the
FDA approved 45 novel drugs, an all-time record high. PharmaCompass has compiled a list of novel drugs approved by the FDA in 2015.The FDA also approved new dosage forms of existing products in the market (email us if you would like a copy), like the 3D printed version of anti-epilepsy drug, Spritam (Levetiracetam).
This week, PharmaCompass focuses on the new dosage
forms of existing drugs that got approved last year.
Modified blockbusters
Improving the delivery form of a blockbuster drug is something that not only helps patients but often successfully extends the patent life of the cash-generating drugs for Big Pharma. Here are some blockbuster drugs that saw their modified versions being launched in 2015:
Jadenu (deferasirox): With
almost a billion dollars in revenues in 2015, Exjade (deferasirox) was approved in 2005 as a
tablet for use in a suspension. Novartis, the innovator,
got approval in March 2015
for Jadenu, a once-daily oral tablet. Jadenu (deferasirox), a new formulation
of Exjade, is the only once-daily oral tablet for iron chelation. Jadenu has
simplified daily treatment administration for patients with chronic iron
overload.
Nexium
24HR (esomeprazole magnesium): Also
known as the Purple Pill, Nexium – Astra
Zeneca’s blockbuster drug for acid reflux that generated annual sales in America of more than US $ 3 billion – went generic in 2015. In order to extend Nexium’s market, Pfizer and AstraZeneca came together to promote an over-the-counter (OTC) version of Nexium. A capsule version of OTC Nexium was approved in 2014 and is known as
Nexium 24HR. Last year, the FDA granted approval to the tablet form of the
drug.
Iressa
(gefitinib): AstraZeneca re-introduced Iressa in
the US market in 2015. The
FDA had approved Gefitinib in May 2003 for non-small cell lung cancer. Approved
as a third-line therapy, in 2010 the FDA requested AstraZeneca to voluntarily withdraw Iressa tablets
from the market, as post-marketing studies had failed
to verify and confirm clinical benefit. Iressa (gefitinib) is now back in the US as a first-line therapy for a type of lung cancer. However, the patent protection is limited – only one listed patent in the Orange Book which expires next year, and five US Drug Master Files already submitted.
Onivyde (irinotecan): Liposomal formulation of anti-cancer
drugs have been in vogue for some time. Merrimack Pharmaceuticals got its novel encapsulation of Irinotecan in a liposomal formulation approved for the
treatment of patients with metastatic pancreatic cancer, sold under the brand
name Onivyde.
Vivlodex (meloxicam): In October 2015, the FDA approved 5 mg and 10 mg (administered once daily) doses of Vivlodex™ (meloxicam) capsules, a nonsteroidal anti-inflammatory drug (NSAID) used for the management of osteoarthritis pain. The previously approved doses for meloxicam capsules were 7.5mg and 15mg. Vivlodex uses a proprietary SoluMatrix Fine Particle Technology™, which contains meloxicam as submicron particles that are approximately 10 times smaller than their original size. The reduction in particle size provides an increased surface area, leading to faster dissolution.
Kalydeco (ivacaftor): A cystic fibrosis drug from Vertex Pharmaceuticals – Kalydeco – has been making headlines
because of its high price (more than US $ 300,000 a year). Price concerns
aside, 2015 saw the launch of a pediatric version of the drug as a ‘weight-based oral granule formulation of Kalydeco that can be mixed in soft foods or liquids’.
Extended release versions
Many of
the approvals granted by the FDA last year were to extended release
formulations (a pill formulated so that the drug is released slowly) of
existing drugs.
Kremers Urban’s
extended release version of Methylphenidate
capsules made headlines last year because of a reclassification of the drug by
the FDA. Under the new classification rating, methylphenidate hydrochloride extended-release tablets can be prescribed but may
not be automatically substituted for J&J’s reference drug Concerta (methylphenidate hydrochloride). Kremers Urban was almost sold last year. But due to this reclassification, investors aborted their US $ 1.53 billion buyout. Kremers Urban was later acquired by Lannett Company Inc.
In
addition, extended-release versions of Aspirin, Carbidopa/Levodopa, Paliperidone Palmitate, Tacrolimus
and Morphine Sulphate also received green signals for a market launch.
First generic opportunities
Last year, PharmaCompass
shared the names of some drugs which had no generic competition and were also
not protected by patents. (Read: “Litigation Free, first generic opportunities list”).
Deferiprone (a drug that chelates iron and is
used to treat iron overload in thalassemia major) met the criteria. But it still
has no generic competitor and is now available as a new dosage form.
Amedra Pharmaceuticals, now owned by Impax Laboratories, has enjoyed the rights to sell Albendazole tablets for almost two decades
without generic competition in the US. Albendazole is a medication used for the
treatment of a variety of parasitic worm infestations. In 2015, patients were
provided access to chewable tablets of Albendazole.
New combinations at work
The FDA also approved
multiple combination drugs where the individual active ingredients had been brought
to market previously.
Most of the combination drugs
approved belong to major pharma players like Novartis, Novo Nordisk, Bristol Myers etc.
Boehringer’s diabetes treatments – Jardiance (empagliflozin) – approved in 2014 and
Tradjenta (linagliptin) approved in 2011, were
combined and the combination drug product Glyxambi was approved in 2015. Another
combination of empagliflozin, with metformin – Synjardy – was also approved in August last
year.
Lesser known companies also
got combination drugs approved. UK-based
development company Vernalis got approval for its cold-cough treatment, Tuzistra XR – an extended release suspension of codeine polistirex and chlorpheniramine
polistirex.
Similarly, US-based biopharmaceutical startup, Spriaso LLC, also
working in the cold and cough therapeutic area, got an extended release tablet
containing codeine phosphate and chlorpheniramine maleate approved.
Symplmed, a company which is
developing various forms of Perindopril, got approval for Prestalia (a
combination of perindopril arginine and amlodipine besylate) for the
treatment of hypertension.
Our view
Each year, the FDA approves several
pharmaceutical drugs in order to improve patient care; and often versions of
these drugs are marketed and distributed across the globe.
PharmaCompass’ list of drugs approved in 2015 is now available – just email us for your copy.
Accelerate your drug development
PharmaCompass has also launched
the Drug Development Assistance tool on its platform.
Simply search for the drug or the active ingredient of your interest, click on the Drug Development icon on the left menu bar and you can see the inactive ingredients used to formulate
the various drug products approved in the United States.
Impressions: 5419
https://www.pharmacompass.com/radio-compass-blog/fda-s-drug-approvals-in-2015-novel-drugs-new-versions-of-existing-drugs
#PharmaFlow by PHARMACOMPASS
14 Jan 2016
Diabetes: Which New Drug is the Safest? FDA Issues Safety Warning on oral Antidiabetic Blockbusters.
Recently launched type 2 diabetes molecules, canagliflozin, dapagliflozin, and empagliflozin, were
served a deadly blow as the FDA recently issued a safety warning regarding their use, leading to a potential life-threatening condition. As almost all diabetes products have some side effect or
the other, we are wondering, which
next generation diabetes drug is the safest?
The recent warning of the U.S. Food and Drug Administration (FDA) says that: “type 2 diabetes medicines canagliflozin, dapagliflozin, and
empagliflozin may lead to ketoacidosis, a
serious condition, where the body produces high levels of blood acids called
ketones, that may require hospitalization”.
The FDA warning
is a severe setback as it limits the options available to reduce
blood sugar without the need for needles.
Ketoacidosis, typically affects type 1 diabetes
patients, but patients using these new molecules were type 2 diabetes and have
developed ketoacidosis. All of the cases highlighted by the FDA involved people
with type 2 diabetes, even if the
condition manifested itself slightly differently than in patients with type 1 diabetes.
These
drugs, are also known as SLGT2 inhibitors. They have been on track for
blockbuster sales and are sold under different brand names.
Table// Brand names for SLGT2 inhibitors (canagliflozin,
dapagliflozin, and empagliflozin):
Company Name
Single Ingredient
Fixed-dose Combination
Johnson & Johnson
Invokana® (canagliflozin)
Invokamet® (canagliflozin and metformin)
AstraZeneca
Farxiga® (dapagliflozin)
Xigduo XR® (dapagliflozin and metformin)
Boehringer
Jardiance® (empagliflozin)
Glyxambi® (empagliflozin and linagliptin)
Blockbuster sales:
Johnson & Johnson, the first to get approval for their SGLT2
inhibitor (canagliflozin) in the United States, reported in 2015 first quarter sales of $278
million, almost triple of their sales for the same period last year.
The quarter-on-quarter growth was almost 40%!
AstraZeneca, on the other hand, had to contend with a dapagliflozin
drug stock out in Canada “due to higher than anticipated demand”.
Actually, the overall sales estimates, for this
class of drugs, have been variable with some analysts believing the annual
sales will be US$2 billion, while others, expect them to reach US$5 billion.
Adverse side
effects:
Despite these success stories, SGLT2 inhibitors have had a bumpy ride in
the approval process with potential cancer risk,
leading to the rejection of the initial dapaglifloxin application by the FDA. This
category of molecules have also been
linked to increased rates of genital and
urinary tract infections, along with kidney damage and cardiovascular issues.
So who will benefit?
All this bad news on SGLT2 drugs could be positive for
another class of anti-diabetic molecules called DPP4 inhibitors.
Merck & Co’s Januvia® (sitagliptin) and Janumet® (sitagliptin and metformin) dominate this category of products with almost $6
billion in 2014 sales. In addition this year, Merck succeeded in demonstrating the cardiovascular safety of Januvia®, which was
not the case for other DPP4 inhibitors like AstraZeneca’s Onglyza® (saxagliptin)
and Takeda’s Nesina® (alogliptin).
While Merck’s Januvia has its own set of concerns (there have
been reports of acute pancreatitis), the risks compare
mildly when associated with other new anti-diabetes drugs.
For Takeda’s other diabetes drug, Actos® (pioglitazone), lawsuits related to cancer risks drove
the company to its first annual loss in six decades. They paid a settlement
of $2.4 billion last month.
While Actos® continues to remain on the market, safety concerns will impact the future sales of diabetes medicines, as they all battle one
of the biggest epidemics challenging public health.
Impressions: 4174
https://www.pharmacompass.com/radio-compass-blog/diabetes-which-new-drug-is-the-safest-fda-issues-safety-warning-on-oral-antidiabetic-blockbusters
#PharmaFlow by PHARMACOMPASS
21 May 2015
