Market Place
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: 2208
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
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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: 54739
https://www.pharmacompass.com/radio-compass-blog/top-drugs-and-pharmaceutical-companies-of-2019-by-revenues
#PharmaFlow by PHARMACOMPASS
29 Apr 2020
PharmaCompass has assessed the second quarter US Drug Master
File (DMFs) filings. In our view, with five potential first-to-file (FTF)
applications along with another five DMFs challenging markets that have been
monopolized for decades, the pharmaceutical industry in the United States
should brace itself for some serious shakeups. Unlike the first
quarter of 2015 where 241 new DMF filings were listed on the USFDA site,
this quarter saw a reduction of almost 35 percent in the DMFs filed. As DMFs
form a critical part of the regulatory submissions made by generics to
challenge innovator companies, a reduction in filings, in the recent quarter,
seems to bear no correlation with the disruption the market will potentially
witness in times to come. The ‘first-to-file’ disruptors Profits in the generic pharmaceutical business are highly dependent on how quickly a drug is introduced in the market. The ‘first-to-file’ generic is a coveted position, since the company is legally granted
a 180-day period of market exclusivity, where no other generic can be in the
market. This six month exclusivity invariably leads to windfall gains for the
company.This quarter DMFs were received by the FDA, which could potentially drive the first-to-file challenges against J&J’s blockbuster Inovkana (canagliflozin), Eisai’s Belviq (lorcaserin
hydrochloride), Incyte’s Jakavi (ruxolitinib
phosphate), Celgene’s Pomalyst (pomalidomide) and Akorn’s Zioptan (tafluprost).However, given the complexities involved in bringing a
generic product to market, the first DMF filing does not always result in the
first generic challenge to the brand drug. The second DMFs filed for a product
are also strong contenders which must not be ignored. For example, Glenmark
recently filed their DMF for tofacitinib,
almost 18 months after serial-DMF filing by MSN
Pharmaceuticals. But Glenmark
has moved ahead by already getting their DMF reviewed by the FDA. Similarly, while Alp Pharma Beijing’s dapagliflozin, Perrigo’s ferric citrate and Amino Chemicals’ miglustat
are the second DMFs to be received by the FDA, the innovator should start
counting the days before they are plagued by generic challengers. Exclusively
not-patentedFor several years, Indian companies have been leading many
first-to-file generic challenges in the United States. However, as they have
scaled up in size, the same companies have also obtained rights to some
exclusive markets in the United States; either through acquisitions or
alliances. Sun Pharmaceutical’s US
$ 230 million acquisition of dermatology specialist Dusa was triggered by the successful sales of Dusa’s photo-chemotherapy treatment, Levulan. German Midas Pharma GmbH’s filing will not only subject Sun’s market domination to generic competition, the fact that there are six other DMFs filed for this product (of which none of the filings have come from Indian or Chinese companies) indicates a change in the way the industry is beginning to operate. Like Sun Pharmaceutical’s monopoly of Levulan, Dr. Reddy’s has enjoyed no competition for their topical treatment, Cloderm (clocortolone
pivalate) since 2011 when they purchased the rights for the product by
making an
upfront payment of US $ 36 million to Canadian, Valeant Pharmaceuticals. Dr. Reddy’s needs to start monitoring the progress of Italian Trifarma’s filing since this is the fifth time a DMF for this product has been received by the FDA.Indian companies aside, Aspen’s Leukeran, Bausch & Lomb’s Zirgan, Mission Pharmaceuticals’ Thiola and GSK’s topical treatment Abreva have
all marketed their products without any competition. The DMF filings of this
quarter indicate that generics have narrowed in on the profits being made and
the market dynamics for these products will change in the future. Down, but not outIntriguingly, companies like Apotex
Pharmachem, Emcure
Pharmaceuticals and Global Calcium
are currently on the FDA Import Alert list and banned from exporting products
to the United States since they did not operate in
conformity with the current good manufacturing practices (GMP's). However, these companies are definitely optimistic about
their future since they have all filed new DMFs this quarter. It remains to be
seen if the bans will get lifted in the near future.This quarter also saw Dr. Reddy’s get creative in their challenge to Japanese Astellas Pharma’s leaky bladder treatment, Myrbetriq (mirabegron).
After having filed a DMF last year, they re-filed again recently, with a
different polymorphic form, to potentially circumvent the patents around this
product. Our supportGeneric pharmaceutical companies are continuously looking
for opportunities where they can get the maximum possible market share in the
fastest way possible. While the number of manufacturers of active pharmaceutical
ingredients (APIs) keep increasing, we are also witnessing an increase in the cost
of regulatory support required to sustain the production of these APIs. The industry is becoming more challenging – identifying target markets is becoming a science which requires high-level management focus. In order to help you, PharmaCompass will share its compilation of this quarter’s DMF filing list. Just send
us an email by clicking here and we’re happy to support you in every possible way.Last week, the FDA also announced the fee dues (as on
October 1, 2015), as per the Generic Drug User Fee Act (GDUFA). We are sharing
the amounts due, in case you have not been able to access this information.
FISCAL YEAR AND FEE TYPE
2014 (Rate)
2015 (Rate)
$ & %
Difference from previous year
Abbreviated New Drug Application
$63,860
$58,730
-$5,130 (-8.0%)
Prior Approval Supplement
$31,930
$29,370
-$2,560 (-8.0%)
Drug Master File
$31,460
$26,720
-$4,740 (-15.1%)
Finished Dosage Form Facility
$220,152 (Domestic)
$247,717 (Domestic)
$27,565 (12.5%)
$235,152 (Foreign)
$262,717 (Foreign)
Active Pharmaceutical Ingredient
Facility
$34,515 (Domestic)
$41,926 (Domestic)
$7,411 (21.5%)
$49,515 (Foreign)
$56,926 (Foreign)
Impressions: 5139
https://www.pharmacompass.com/radio-compass-blog/generic-challenges-the-next-first-to-files-gdufa-dues-fy-2016-and-more
#PharmaFlow by PHARMACOMPASS
13 Aug 2015
