The year
2021 was eclipsed by the Covid-19 pandemic. In our update for the first half of 2020, we had mentioned that
Covid-19 has not slowed down the speed at which generic active pharmaceutical
ingredient (API) manufacturers were submitting Drug Master Files (DMFs) to the
US Food and Drug Administration (FDA). That trend continued in 2021, when the
speed of DMF submissions to the agency remained similar to that witnessed in
the previous years.
In fact,
Type II DMFs, or DMFs for active pharmaceutical ingredients (APIs), were higher
in 2021 as compared to previous years. In the first quarter, FDA received 164
Type II DMF submissions, which rose to 165, 166 and 172 submissions over the
next three quarters. In all, 667 Type II DMFs were filed in 2021, as opposed to
662 in 2020, 633 in 2019 and 644 in 2018.
DMFs are
submissions made to the FDA by manufacturers who provide the agency with
confidential, detailed information about facilities, processes or articles used
in manufacturing, processing, packaging and storing of human drug
products.
Overall,
2021 saw a total of 913 DMFs (Type II, III, IV and V) being submitted. In
comparison, FDA had received 931 DMF submissions in 2020, 894 in 2019 and 979
in 2018.
View FDA DMF Filings in 2021 (Power BI Dashboard, Free Excel Available)
India
continues to lead DMF filings, followed by China
Country-wise
data on DMF filings at
the FDA tells us the potential of a country in the field of pharmaceuticals. At the company-level, with each DMF filing, a firm commits itself to manufacturing drugs in a facility that is aligned to the FDA’s rules and regulations.
This year
too, DMFs filed from India and China were significantly higher than those from
other countries. Expectedly, India continued to lead with 376 DMF filings.
Submissions from India were over twice that of DMF filings from China (at 159).
This is not surprising since the two countries have the maximum number of API
manufacturing facilities registered with the FDA.
As compared
to this, the United States had 52 DMF filings, Italy had 10, Spain and Taiwan
had 9 each, and countries like Canada, Israel, Japan and UK had five DMF
filings each.
View FDA DMF Filings in 2021 (Power BI Dashboard, Free Excel Available)
India’s MSN Labs leads DMF count
As in the
past, India's MSN Laboratories continued to lead the DMF filings by a single company with 43 submissions. MSN was followed by five other Indian companies — Dr. Reddy’s Laboratories filed 15 submissions, Hetero Group and Aurobindo Pharma 14, Metrochem API 13 and Aurore Life Sciences filed 12 DMF submissions.
The only
Chinese company in the top 10 by DMF count was Brightgene Bio-Medical Technology Limited with nine DMF submissions.
The maximum
number of DMF filings were for semaglutide (eight), followed by favipiravir (seven), apalutamide (six), sitagliptin phosphate (six) and tofacitinib citrate (six). Others like acalabrutinib, elagolix sodium, lenalidomide, liraglutide and pantoprazole sodium had five DMF filings each.
View FDA DMF Filings in 2021 (Power BI Dashboard, Free Excel Available)
Slow
assessment review, higher GDUFA fee
Although
there were 667 Type II DMFs filed with the FDA, only 194 (or 29 percent) had
their review completed. The GDUFA (short for Generic Drug User Fee Amendments)
fee associated with a DMF assessment review for 2021 was considerably higher — at US$ 69,921 — as opposed to US$ 57,795 for 2020. For FY 2022, the GDUFA fee has been revised upward to US$ 74,952 (an increase of US$ 5,031).
There are 42
products for which a DMF was filed for the first time. Among the patented
products which should expect generic competition are avatrombopag, encorafenib, esketamine hydrochloride, siponimod fumaric acid, tedizolid phosphate and vorapaxar sulfate.
In fact,
DMFs were also filed for products that are yet to receive an FDA approval. Some of these products are imeglimin, aviptadil, gimeracil, linzagolix choline, meglumine antimoniate, roluperidone hydrochloride and teneligliptin.
View FDA DMF Filings in 2021 (Power BI Dashboard, Free Excel Available)
Our view
The Covid-19
pandemic revealed how the global supply chain for pharmaceuticals is excessively dependent on India and China. As a
result, many countries across the world are making investments into expanding
their API production capacities. This should translate into more Type II DMF
filings from countries other than India and China.
Moreover, as the pandemic begins to wane and the FDA increases its inspections — both domestic and international — compliance issues are bound to increase. The US is planning to run a pilot program
soon that will test a system of unannounced inspections in India and China.
Companies in both India and China will need to increase their focus on
compliance if they wish to continue to be major contributors to the global
supply chain for pharmaceuticals. We can certainly expect more regulatory news
in 2022.View FDA DMF Filings in 2021 (Power BI Dashboard, Free Excel Available)
Impressions: 5386
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: 54763
2017 was a landmark
year for the pharmaceutical industries in the US and Europe, with a sharp
increase in the number of new molecular entities (NMEs) being approved in both
the geographies.
The US Food and Drug Administration (USFDA) approved 46 NMEs
in 2017, a strong bounce back from only 22 NMEs approved in 2016.
The
46 approvals by the USFDA’s Center
for Drug Evaluation and Research (CDER) is the
second highest total since 1996 when 53 NMEs were approved.
In
Europe, the European Medicines Agency (EMA) approved 35 drugs with a new active
substance, up from 27 in 2016. We also identified eight drugs that got approved
in Europe before winning the USFDA nod.
This
week PharmaCompass shares its compilation of the 46 novel drugs approved
in the US, of which 34 (or 74 percent) were small molecules and 12 (or
26 percent) were biologics, which were approved by the USFDA.
Click here for our list of FDA’s Novel Drug Approvals in 2017 (Excel version available) for FREE!
We
have also evaluated these new
drug therapy approvals with regard to their estimated sales potential. While
the sales estimates of a new drug are far from certain, our effort is directed
at providing insights into the potential these drugs hold along with attempting
to identify emerging market trends.
An
overview of USFDA’s approvals
The USFDA’s CDER focusses extensively on the approval of novel drugs “which are often among the more innovative products in the marketplace, and/or help advance clinical care by providing therapies” that have never before been marketed in the United States.
In addition, CDER
also looks at new and expanded uses of USFDA-approved drugs. In 2017, the CDER
also worked on approving five new biosimilar drugs, which are highly similar to
the USFDA- approved
therapeutic biological products.
Click here for our list of FDA’s Novel Drug Approvals in 2017 (Excel version available) for FREE!
New formulations or
new manufacturers of USFDA-approved products that can provide advantages over
original products, such as being able to take the drug on an empty stomach and
not with food, were also approved.
New dosage forms
entered the market that add value to already approved drugs, such as chewable
tablets for patients unable to swallow pills and Abilify MyCite (aripiprazole
tablets with a sensor).
Aripiprazole was
first approved by the USFDA in 2002 as a tablet to treat patients with
schizophrenia and was marketed under the brand name Abilify.
In 2017, Abilify MyCite
was approved as a tablet which contains an electronic sensor. Abilify MyCite
allows the patient to track whether he or she has taken the medication via a
smartphone or the cloud.
Patients can also
give their caregivers or physicians access to the information through a
web-based portal.
Click here for our list of FDA’s Novel Drug Approvals in 2017 (Excel version available) for FREE!
In the list of 2017 approvals, CDER identified 15 of the 46 novel drugs approved in 2017 (33 percent) as first-in-class while 18 drugs (39 percent) were approved to treat rare or “orphan” diseases that affect 200,000 or fewer Americans.
Of the 46 novel drugs
approved in 2017, 36 (78 percent) were approved in the United States before
receiving approval in any other country.
The American stars of 2017, by sales revenue
Of all the drugs
approved by the USFDA, the highest expectations are from Regeneron and Sanofi’s first-in-class monoclonal antibody (mAb) — dupilumab. The (IL)-4 receptor subunit-α antagonist has shown benefits in various kinds of inflammatory and allergic diseases.
While the USFDA approved the drug for atopic dermatitis, it is also being developed for asthma, chronic obstructive pulmonary disease (COPD) and other indications.
Evaluate Pharma analysts estimate the sales of dupilumab
at US$ 4,938 million by 2022.
Click here for our list of FDA’s Novel Drug Approvals in 2017 (Excel version available) for FREE!
Expectations are also
high from two other mAb products. Genentech and Roche’s anti-CD20 mAb ocrelizumab for relapsing and primary
progressive forms of multiple sclerosis is expected to bring in US$ 4,088
million by 2022 while Pfizer’s avelumab, an anti-PD L1 cancer drug
co-developed along with Merck KGaA, which was approved to treat metastatic
Merkel cell carcinoma, is expected to achieve peaks sales of US$ 4-6 billion
with an estimated US$ 3 billion in annual sales for Pfizer.
In late 2015, AstraZeneca partnered with Acerta Pharma to develop a potential best-in-class irreversible oral Bruton’s tyrosine kinase (BTK) inhibitor — acalabrutinib.
AstraZeneca
acquired 55 percent equity in Acerta for an upfront payment of US$ 2.5 billion
and should have completed its payment of an additional US$ 1.5 billion now that
the USFDA has approved the cancer drug, which is estimated to have peak sales
of US$ 2,500 million.
Click here for our list of FDA’s Novel Drug Approvals in 2017 (Excel version available) for FREE!
Also
expected to bring in US$ 2,500 million in sales is Novartis’ treatment for postmenopausal women with a type of advanced breast cancer — ribociclib. While the USFDA
approved the drug in March 2017, the EMA
approved it in August 2017.
The
European specials of 2017
While
many drugs were approved in the United States before being approved in Europe, PharmaCompass
has identified 8 active substances which have not been approved in the US but
got EMA approval in 2017.
AstraZeneca’s treatment for hyperkalaemia — Lokelma (sodium zirconium
cyclosilicate) — got approved by the EMA. However, the FDA did not approve it after the agency raised concerns over the manufacturing of the drug following an inspection of the facility.
Lutathera
— a nuclear medicine targeted at the type of cancer that killed former Apple Inc co-founder and CEO Steve Jobs — got approved by the EMA and its developer Advanced Accelerator Applications (AAA), who in turn got bought over by Novartis for US$ 3.9 billion.
The
application for Lutathera has been filed with the USFDA. Under the Prescription
Drug User Fee Act (PDUFA), the agency is scheduled to make a final approval
decision this week (on January 26, 2018).
Tivozanib
(Fotivda, an oral, once-daily, vascular endothelial growth factor or VEGF) tyrosine kinase inhibitor (TKI)
discovered by Kyowa Hakko Kirin and approved for
the treatment of adult patients with advanced renal cell carcinoma was also
approved in Europe before getting the nod in the US.
Our view
While the USFDA’s CDER approved the highest number of drugs in two decades, the approvals of the year were done by USFDA’s Center for Biologics Evaluation and Research (CBER) which approved two cell-based gene therapies.
Novartis’ Kymriah (tisagenlecleucel), the first-ever gene therapy — known as CAR-T (short for chimeric antigen receptor T-cell) — was approved for certain pediatric and young adult patients with a form of acute lymphoblastic leukemia (ALL).
In its press statement, the USFDA described this as a “historic action”.
CAR-T is a type of cancer immunotherapy
that harnesses the body’s immune system to fight cancer cells. In this case, the therapy removes a person’s cells, reengineers them and then puts them back in their body to attack cancer cells.
In CAR-T therapy, every single dose of the
treatment is unique and completely personalized to the patient. The Novartis drug came with a list price of US$ 475,000 for a one-time treatment.
Click here for our list of FDA’s Novel Drug Approvals in 2017 (Excel version available) for FREE!
Gilead also
bet big on the technology and acquired Kite Pharma for US$ 11.9 billion in
August. The USFDA also approved Kite’s most advanced CAR-T therapy candidate — axicabtagene ciloleucel (axe-cel).
Gilead announced a price significantly lower than the launch price at which Novartis
is selling its CAR-T treatment (Kymriah).
With Novartis and
AstraZeneca getting three therapies approved, Pfizer, Roche, Valeant and the
team of Sanofi and
Regeneron bagging two each
and almost half the drugs approved by the USFDA’s CDER in 2017 expected to generate more than US$ 1 billion in sales, things look promising for innovation in pharmaceuticals and also provide interesting
opportunities for generic drug manufacturers.
Click here for our list of FDA’s Novel Drug Approvals in 2017 (Excel version available) for FREE!
Impressions: 14351