Market Place
This week, Phispers brings you the
latest on the Ranbaxy-Daiichi and Merck-Gilead cases. There is also news on
Medtronics, which faces a whistleblower lawsuit. And Valeant, which has come
under the scanner for allegedly defrauding insurers. Our compliance roundup
updates you on companies across the world that faced regulatory action
recently. Singapore court’s 373-page order reveals how Ranbaxy withheld information from DaiichiLast week, a report in The Indian Express brought to light how Ranbaxy deliberately withheld information from Japan’s Daiichi Sankyo in the Ranbaxy-Daiichi case. The information was based on a copy of the Singapore International Arbitration Centre’s (SIAC) order, passed in April 2016. The former owners of Ranbaxy – Malvinder Singh and Shivinder Singh – face a penalty of Rs 35 billion (US $ 523 million) and have until August 22 to challenge the SIAC order. The information implicates the Ranbaxy top brass in a “in a slew of irregularities, from fraud to falsehood.” In over 373 pages, the SIAC order lays out what it calls “the path of deception that Ranbaxy took and how it kept Japan’s Daiichi Sankyo — which bought Ranbaxy in 2008 for Rs 198 billion (US $ 2.96 billion) — in the dark even a year after its purchase”. The SAIC order was based on a 2004 Self-Assessment Report (SAR) prepared by the then head of research and development of Ranbaxy, Rajinder Kumar, for the company’s internal use. The contents of an internal report were not shared with Daiichi. The SAR listed
over 200 drugs, including antiretroviral drugs for treating AIDS patients, for
which Ranbaxy allegedly used fabricated data to bag approvals from regulators
and authorities of more than 40 countries. Compliance roundup: Chinese, Indian, American and Spanish firms in compliance troubles Notice of non-compliance to Artemis Biotech: Artemis
Biotech, a division of Themis
Medicare in India, received a notice
of non-compliance from European regulators. According to the regulators,
the company had violated basic principles of data integrity within its instrument
laboratory. And the relevant GMP data was outside the control of the quality
management system. As an outcome of the inspection, the Certificates of Suitability (CEPs) granted for popular cholesterol lowering ingredient – simvastatin – have been suspended. Just three months ago another Indian manufacturer – Krebs
Biochemicals & Industries – had its CEPs suspended for the same product.Alcor found to have unsuitable facilities: A Spanish manufacturer – Alcor SL – that manufactures liquid syrups for use in Spain was found not to have suitable facilities, personnel and materials to ensure proper compliance with GMP during an inspection in June this year. Although the company responded with a corrective action plan, it was found “insufficient”.Claris recalls injections in the UK: Indian manufacturer Claris
Lifesciences recalled
Furosemide
injections in the United Kingdom as they had been inadvertently distributed in
the country. The product was intended for sale in Australia. FDA’s warning letters to Zhejiang Medicine, Concept Products: While
there was activity in Europe, the FDA issued a warning
letter to Zhejiang
Medicine (Xinchang Pharmaceutical Factory), a manufacturer of antibiotics
like levofloxacin,
daptomycin
and vancomycin,
for data integrity violations. Laboratory personnel were found “disguising testing”. The personnel were conducting unofficial testing that was being recorded in separate ‘R&D’ folders before conducting the officially reported sample analyses. Analysts were also found signing
and dating microbiological testing laboratory worksheets five days before the
test results were available and backdating laboratory worksheets for impurities
and content testing by four days.The FDA also issued a warning
letter to a Chinese manufacturer, Concept Products Limited, for “significant violations of cGMP regulations for finished pharmaceuticals”. It placed yet another Indian company Laxachem Organics and Chinese firm Yangzhou
Hengyuan on import alert. Warning letter to Noven: A US-based patch manufacturer – Noven
Pharmaceuticals – received a warning
letter over quality concerns uncovered in its transdermal drug delivery
systems (TDDS) such as Minivelle
and Daytrana.
The FDA expressed concerns over the scientific soundness of the company’s measurement method since the FDA stated that “your unsound methods could be masking product failures” and leading “to product detachment, expose the drug to other people, and other safety issues.” Now, Merck has to pay Gilead’s US $ 200 million legal feeIn March this year, Merck
had won a legal dispute over sofosbuvir,
the API in Gilead's
multibillion-dollar drugs Sovaldi and Harvoni.
The federal jury had ordered Gilead to pay Merck US $ 200 million in damages
for infringing on patents for the hepatitis C drugs. But
in June, the US Dristrict Judge Beth Labson Freeman threw out Merck’s victory and snatched back the US $ 200 million Merck had been awarded. Last week, the same judge added insult to Merck’s US $ 200 million-injury. Freeman said Gilead was entitled to relief from legal fees it had incurred while defending its case.Merck has been handed a US $200
million bill for Gilead's
legal fees. Merck now intends to appeal in the case, saying the judge’s ruling “does not reflect the facts of the case.” FDA launches improved web-based version of its Orange BookThis week, the US Food and Drug
Administration (FDA) launched an improved
web-based version of its Orange Book – a publication on drugs approved on the basis of safety and effectiveness. The Orange Book is widely used by doctors and by the regulatory community for identifying which drug products are substitutable for one another. The improved Orange Book has an updated design and has more user-friendly search optionsFormerly known as the Approved
Drug Products with Therapeutic Equivalence Evaluations, the Orange Book had
first appeared as a published list in 1980. It came online in 1997. Valeant allegedly defrauded insurers, may be under criminal
investigation In one of the most serious probes
faced by Valeant
Pharmaceuticals, the Canada-headquartered company may be under criminal investigation over allegations that it defrauded insurers by hiding its ties with a mail-order pharmacy – Philidor – that boosted its sales. Prosecutors are probing whether
Philidor made false statements to insurers about its ties with Valeant, while
helping patients get coverage for the higher-priced Valeant drugs. According to
a report published in The Wall Street
Journal, criminal charges are likely to be levied against former Philidor
executives and against Valeant as a company. The relationship between Philidor
and Valeant has been under the scanner since October 2015, when questions were
raised about Valeant's accounting. Novartis to expand capacity of monoclonal antibody plant in EuropeNovartis
is investing
US $ 100 million to expand its monoclonal antibody (mAb) capacity at a
plant in Europe. The Swiss drugmaker has committed about US $ 1 billion to
boost its biosimilar production in order to emerge a leading player in
biosimilars. Novartis is beginning work on the mAb project that will boost
capacity by 70 percent at the Novartis biotechnology center in Huningue,
France. Meanwhile, the company has
acknowledged that employees in South Korea may have been involved in rebate
trickeries. But it says an investigation of similar accusations
in Turkey uncovered no problems. In Turkey, Novartis considers the matter
closed.In April, a prosecutor in Turkey
had reportedly opened an investigation after receiving a copy of an email sent
by an anonymous whistleblower to Novartis CEO saying the unit there paid
consultants US $ 290,000 in 2013 and 2014 to win about US $ 85 million in
business from government hospitals.Matters in South Korea are a lot serious. In South Korea, prosecutors want the government to suspend the company’s operations there after they indicted half-dozen executives for issuing improper rebates. German watchdog criticizes efforts to accelerate new drug approvalsGermany’s cost-effectiveness watchdog – the German Institute for Quality and Efficiency in Health Care – has criticized
an effort by European regulators to accelerate approval for new medicines
based on limited evidence. These concerns come at a time when regulators on both
sides of the Atlantic are looking for new approaches to fulfill unmet
medical needs through faster approval of drugs.Adaptive pathways approach is a term
used to describe a method for jumpstarting drug approvals for select patient
populations. Two years ago, the European Medicines Agency (EMA) had launched a
specific pilot program in this direction. However, the German watchdog
maintained that the EMA failed to make its case that this approach for
approving drugs can make a demonstrable difference. Medtronic faces
whistleblower lawsuit for using devices under false pretensesMedtronic, a major medical device manufacturer, is facing a whistleblower lawsuit that claims it sought FDA approval for its devices under false pretenses. The devices were being regularly used for a purpose they weren’t intended to be used by the regulators.According to Dr. Vikas Saini, president of the Lown Institute, a Boston healthcare think tank, who has been following the case, the devices had been labelled ‘not for cervical spine use’. “Yet, in everything about them, including emails from their marketing folks, it makes clear that they were meant to be and were used in the cervical spine,” Saini said.Medical devices are lightly regulated by the FDA. Once
cleared by the FDA, physicians used medical devices however they deem fit. Questions being
raised on health of Clinton, Trump Donald Trump and Hillary Clinton are two of the oldest presidential candidates in the US history. While Clinton’s doctor certified that she “is in excellent physical condition” and Trump’s physician declared he would be “the healthiest president – ever”, these testaments are not being taken seriously in the absence of detailed medical records. Both Trump’s and Clinton’s doctors released brief
assessments of their health recently. Television host Sean Hannity has aired a series of segments on Fox that cast doubts on Clinton’s health. Democrats, on the other hand, have been questioning Trump’s mental health. One congresswoman recently suggested he should undergo a “mental fitness test.”
Impressions: 5118
https://www.pharmacompass.com/radio-compass-blog/ranbaxy-s-path-of-deception-revealed-in-singapore-court-order-chinese-indian-american-and-spanish-firms-in-compliance-troubles
#PharmaFlow by PHARMACOMPASS
18 Aug 2016
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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
In August, when Fortune magazine
published its latest ranking of the fastest-growing companies in the US, topping the list wasn’t a ‘sexy Silicon Valley startup’, but a little known, 73-year-old Philadelphia-based generic drug-maker – Lannett Company Inc.Last
week, Lannett announced it would buy Kremers Urban
Pharmaceuticals Inc – the US generic business of Belgian drug-maker UCB SA – for US $ 1.23 billion.With
the growth demonstrated by Lannett, coupled with the combined revenues of more than US
$ 800 million for the 12 months ended June
30, 2015, the company seems to be on track to become the next
billion-dollar generic pharmaceutical company. However, back in 2002, Lannett’s sales were only US $ 25.1 million. This week, we focus on the secret recipe
that has driven Lannett’s business success. Focus on a few old
productsLannett’s net sales in 2014 were US $ 274 million, an increase of 81 percent over the previous year. However, unlike most companies that generate sales growth through global scale and multiple products, Lannett’s results are an outcome of their extremely strong focus on a few key products sold in the United States.Lannett’s top five products accounted
for 74 percent of the total 2014 sales and two products – Levothyroxine Sodium and Digoxin – generated combined sales of almost US $ 157 million in 2014 (higher than Lannett’s 2013 sales, which were US $ 151 million). Lannett’s two-trick ponyLevothyroxine Sodium tablets remain one of the most
prescribed drugs in the US and are used by patients of various ages and
demographic backgrounds for the treatment of thyroid deficiency. Although an
old drug, it is also a narrow therapeutic index drug that saw serious and continuing
recalls in the 1990s. In 1997, the FDA mandated New Drug Applications (NDA) for this previously ‘grandfathered’ drug (a drug approved before 1938). A year later,
Jerome Stevens
Pharmaceuticals (JSP) filed and received the first NDA approval
by the statutory deadline; beating out the innovators (Abbott Laboratories and King Pharmaceuticals).In 2004, Lannett entered into an agreement with JSP for the exclusive distribution rights of three
product lines in the United States, which included Digoxin and Levothyroxine
Sodium tablets.Today, Levothyroxine Sodium tablets are produced and marketed with 12 varying potencies and are the single-largest revenue contributor for
Lannett. The franchise still
enjoys limited
generic competition, witnesses
year-over-year growth in total prescriptions and most notably has “dollar sales” gains generated by improved product pricing.The
second-largest revenue contributor for Lannett is Digoxin, another drug used in
a narrow therapeutic index to treat
congestive heart failure in patients. Lannett held only 14 percent of
the market until a few years ago and the brand leader, with 61 percent market share was Mylan. The
production of Digoxin tablets was outsourced by Mylan to Amide, a company which ran into such severe product quality and cGMP (Current Good Manufacturing Practices) problems that Mylan not only had to recall their “obese” Digoxin tablets from the market but also had their market share completely wiped out. A few months later, Sun Pharmaceutical’s US subsidiary – Caraco – had a similar issue of obese tablets which made Lannett the undisputed market leader in this niche segment. Realizing substantial price hikesRecently,
Digoxin also witnessed a price increase by as
much as 884 percent from October 2012 to June 2014, which increased its contribution to US $ 54.7 million of Lannett’s total sales of US $ 274 million in 2014. Lannett’s ability to operate in niches where competition is limited and the realization of substantial price hikes possibly led to ‘interrogatories and subpoena from the State of Connecticut Office of the Attorney General’ in July 2014, questioning the Digoxin price hikes. A firm commitment
to partnershipsPrice increases aside, Lannett’s growth has also been an outcome of a stable supply chain partnership with JSP, combined with a strong historical record of regulatory compliance. JSP has accounted for more than 60 percent of Lannett’s overall finished goods inventory purchases in the last few years.However, unlike others in the industry, who have reduced
their focus on manufacturing viewing it as a cost, rather than a value, Lannett
extended their original agreement with JSP. The agreement – scheduled to expire in 2014 – was renewed by not only giving written assurances of a minimum purchase commitment of US $ 31 million annually until 2019, but also issuing 1.5 million shares of Lannett common stock to JSP.“Our distribution agreement with JSP has been highly successful and mutually rewarding,” said
Arthur Bedrosian, Chief Executive Officer, at the time of the agreement
renewal. Lannett’s commitment to partnerships is also mentioned in its annual reports where it mentions partnerships with “Azad Pharma AG, Swiss Caps of Switzerland, Pharma 2B (formerly Pharmaseed), The GC
Group of Israel and HEC Pharm Group, as well as domestic companies, including JSP, Cerovene,
and Summit Bioscience LLC”. The joker in the packLannett’s ambitions to grow have been made clear, given that the Kremers Urban buyout was valued at almost five times Lannett’s current revenues. In addition, they beat out the China Grand group, India’s Cipla Ltd and several
other private-equity firms who were among the potential
bidders for Kremers Urban.Kremers Urban was almost sold late
last year
to private-equity firms Advent International and Avista Capital Partners for US $ 1.53 billion. The deal was called off when one of Kremers Urban’s main products – a generic version of the drug Concerta (methylphenidate hydrochloride) – underwent a change of classification at the FDA. Under the new
classification rating, its methylphenidate hydrochloride extended-release
tablets can be prescribed but may not be automatically substituted for Concerta
at pharmacy counters.Kremers Urban was
requested to provide additional information showing bio-equivalency to Concerta
for which the final results of new bioequivalence studies were submitted this
June. The contingency
payments in the Lannett deal are tied to the FDA restoring the rating and should this happen, the
landscape would once again be familiar territory for what Lannett has
experienced, and capitalized on previously with Levothyroxine and Digoxin! Our viewLannett has
grown using old-fashioned rules of doing business but also adapted to the evolving
environment. They focused
on essential products, obsessed over quality, treated their suppliers as
partners, while also ensuring that the company seizes maximum possible returns
out of an opportunity. Undoubtedly, there are several learnings in Lannett’s story for other pharma companies to emulate.
Impressions: 7594
https://www.pharmacompass.com/radio-compass-blog/how-little-known-lannett-may-soon-become-a-billion-dollar-generic-company
#PharmaFlow by PHARMACOMPASS
10 Sep 2015
Wouldnt it be wonderful if the products that are manufactured, have such great demand that, they fly off the shelves?
Our
assessment of the drug shortage list in U.S. and Canada provides a list of opportunities,
which are an outcome of shortage of the active pharmaceutical ingredient (API).
While
manufacturers struggle with ideas, we list opportunities that pharmaceutical
companies can capitalize upon.
Not all shortages are an outcome of manufacturing delays or quality problems; the growing demand for some products (especially injections) and lack of API supply of others is something that, if addressed, can become a potential windfall for companies (Read Forbes Millions to be made onGeneric Drugs?).
Old, established active ingredients, with
limited supply options are usually the ones which have been driven to shortage. Utilizing the Pharma Compass database, a comprehensive list of existing and alternate supply options was prepared to assist the industry get started
Product
Dosage Form
Active DMFs
Other potential suppliers
Trimipramine Maleate
Capsule
Sanofi-Aventis
Lundbeck
R. L. Fine Chem
Tiopronin
Tablet
Okami Chemical Industry
Methylphenidate HCl
Tablet, capsule
Cambrex,Charles City
Chattem Chemicals
Euticals inc
Johnson Matthey
Mallinckrodt
Noramco inc
Rhodes Technologies Inc
Siegfried USA
AbbVie
BASF Pharma
Centaur Pharmaceuticals
CF Pharma
Harman Finochem
Janssen Pharmaceutica
Macfarlan-Smith
SCI Pharmtech
Sun pharmaceutical
Fluoxymesterone(Androxy)
Tablet
Cedarburg Pharmaceuticals Inc
Acetohydroxamic Acid
Tablet
Isochem Sa
Methyldopate HCl
Injectable
Seratec
Fomepizole
Injectable
Apicore US LLC
Cambridge Major Labs
Navinta LLC
Seratec
Strem Chemicals
Boehringer Ingelheim facilities in St.
Petersberg, Virginia, while listed have been excluded from the list on account
of them shutting down the facility and subsequent plans
of re-starting it not materializing.
Preventing drug shortages is a key focus
area for the USFDA and Health Canada. For this reason, not only do the regulatory
agencies have websites which lists all the shortages, but the USFDA has also developed their own mobile app to address concerns of all the
stakeholders.
Addressing drug shortages is smart business
since it ensures product availability, affordability and assurance along with
profitability for the industry.
Impressions: 3478
https://www.pharmacompass.com/radio-compass-blog/wanted-opportunities-in-the-drug-shortage-list-apis-urgently-needed-in-us-and-canada
#PharmaFlow by PHARMACOMPASS
03 Apr 2015
