A review of the Drug Master Files (DMFs) submitted to the United
States Food and Drug Administration (FDA) from October 2016 to March 2017 (the
fourth quarter of 2016 and the first quarter of 2017) indicates an extremely
robust pharmaceutical industry in India. However, the filing make one question
an article we had carried earlier this month on the end of India’s pharma honeymoon.
India filed more than half the DMFs submitted
Indian companies filed more than half (176) of the 345 DMFs
submitted with the FDA. China (60) came a distant second, followed by the
United States (40). While DMF submissions were made from 26 other countries,
the activity levels seen were a far cry from what was seen in India and
China.
In our past compilation for the second and third quarters of 2016,
Macleods Pharmaceuticals (14 DMFs) had pipped MSN Laboratories (13 DMFs) to become the leading filer from
India.
However, in the recent review period, MSN bounced back with 41 DMF
submissions, compared to six for Macleod. Leading Indian pharmaceutical majors
such as Aurobindo,
Sun Pharma, Amneal,
Mylan’s
India operations, Hetero,
Cipla
and Jubilant
had six or more filings each.
Ajinomoto’s
North American operations filed 11 DMFs for various amino acids and led the
submissions for products manufactured in the United States.
Tianjin Weijie Pharmaceutical led the pack from China, with eight DMF
submissions.
Over the review period, a total of 345 submissions were made to the
FDA, almost similar to the 379 DMFs filed during the second and third quarters
of 2016.
Click here to view all the DMF submissions in Q4 2016 and Q1 2017 (Excel version available) for FREE!
The next FTF challenges
Since APIs form the building blocks of finished formulations, DMF
submissions give a sneak preview into the next possible first-to-file (FTF)
generic challenges to patented drugs.
In
December 2016, Indian drug major Sun Pharmaceutical Industries
announced it will acquire a branded oncology product, Odomzo,
from Novartis
for an upfront payment of US$ 175 million.
A little over three months after the announcement, MSN Labs filed the first DMF for Odomzo’s active pharmaceutical ingredient (API), sonidegib phosphate. Odomzo was approved by the FDA in July
2015 and is indicated for the treatment of adult patients with locally advanced
basal cell carcinoma.
While patents for Novartis’ drugs Tafinlar
and Mekinist
are not scheduled to expire until 2029, Novartis should prepare for a generic
competitor as DMFs were filed for the APIs used in both drugs by MSN Labs. The
drugs had combined sales in 2016 of US$ 672 million.
Click here to view all the DMF submissions in Q4 2016 and Q1 2017 (Excel version available) for FREE!
In addition, MSN Labs also filed the first DMF for nintedanib esylate, the API used in Boehringer Ingelheim’s idiopathic pulmonary fibrosis treatment,
Ofev, and for cabozatinib (S)-malate, the API used by Exelixis for its kidney cancer treatment — Cabometyx.
While in most cases MSN’s DMF is the first one to get filed, in the case of Helsinn’s
Akynzeo,
which is used to prevent chemotherapy-induced nausea and vomiting, Apicore US also filed a DMF along with MSN.
Although sales forecasts for Bayer’s pulmonary arterial hypertension treatment — Adempas (riociguat) — were lowered as the drug did not get the expected sales start
and planned label expansions did not materialize, this did not stop MSN Labs
from filing the first DMF for this product as well.
Click here to view all the DMF submissions in Q4 2016 and Q1 2017 (Excel version available) for FREE!
Another drug which is struggling to meet analyst expectations is Novartis’ Entresto. Once considered “one of the most important products in the company's history” with an expectation to reach US$ 10 billion in peak sales, the drug generated sales of only US$ 170 million in 2016. Regardless, Mylan filed the first DMF for the API.
Another drug where MSN Labs did not file the first DMF was for AstraZeneca’s
ovarian cancer treatment, Lynparza (olaparib).
Alp Pharm Beijing submitted the DMF for the drug which
generated US$ 218 million in sales in 2016 and a figure Bernstein Research
analyst Timothy Anderson forecasts will grow to US$ 684 million by 2020.
The onslaught on Novartis’ portfolio is not limited to only patented products as Lamprene,
a product which has been on the market since 1986, and not had any generic
competitor, had Zhejiang Huahai file a DMF indicating a generic competitor maybe on the horizon
soon.
Mylan’s Sotradecol
has been the only injectable form of sodium tetradecyl sulfate
on the market since 2004. That monopoly may end soon as the FDA completed the
review of a DMF filed for the API early this year.
Click here to view all the DMF submissions in Q4 2016 and Q1 2017 (Excel version available) for FREE!
Most actively filed products — vortioxetine hydrobromide and dolutegravir sodium
The most actively filed DMFs, with seven filings each, were those
for Takeda’s
depression drug Trintellix (vortioxetine hydrobromide) and GSK’s HIV treatment dolutegravir sodium.
Johnson & Johnson’s diabetes treatment Invokana (canagliflozin), which recently demonstrated that it
decreased the risk of heart attacks and strokes, while increasing the risk of amputation,
particularly of toes, had six new DMFs filed.
There were also six new DMFs filed for apremilast,
five for darunavir
and four each for dapagliflozin
and rivaroxaban.
Click here to view all the DMF submissions in Q4 2016 and Q1 2017 (Excel version available) for FREE!
Filings for new drugs under development
Helsinn is moving ahead with the filing of anamorelin hydrochloride, as it filed DMFs for the API and the 100
mg tablets, a product which was welcomed enthusiastically by oncology experts as it raised hopes to
be a drug for cancer cachexia, the extreme wasting seen at the end stages of
the disease.
But those hopes were recently dashed, as a review of the clinical
data by the European Medicines Agency's Committee for Medicinal Products for
Human Use (CHMP) found only "marginal" effects and recommended that
the product be refused marketing authorization in Europe.
Now it remains to be seen what the FDA’s verdict on this drug will be.
Click here to view all the DMF submissions in Q4 2016 and Q1 2017 (Excel version available) for FREE!
AB Science’s Masitinib has been in the news recently as an EMA committee announced the drug, developed for a range of cancers, could not be approved due to “serious failings” in the way clinical studies were conducted.
However, this did not stop Excella GmbH from filing its second DMF for the API.
Multiple sclerosis treatment dimethyl fumarate (Biogen’s Tecfidera) generated
sales of US$ 3.97 billion in 2016 and is projected to achieve US$ 5.56 billion by 2020.
While there are now 28 DMFs filed for dimethyl fumarate, in March
this year Alkermes
announced the initiation of a new phase 3 study
of ALKS 8700, a novel, oral monomethyl fumarate (MMF) prodrug candidate in
development for the treatment of relapsing forms of multiple sclerosis.
It remains to be seen when Alkermes’ product will get approved. However, MSN Labs followed Honour Labs to file the second DMF for this product.
Click here to view all the DMF submissions in Q4 2016 and Q1 2017 (Excel version available) for FREE!
A new submission for deslorelin acetate
(an injectable gonadotropin releasing hormone super-agonist) indicates there
maybe a new drug development underway for this age-old peptide as currently
there are no approved drugs in the US.
A similar situation seems to exist for taurolidine,
an antimicrobial that seeks to prevent infections in catheters.
Vasudha Pharma’s filing of cisapride monohydrate comes as a surprise. The product, which
was launched by Janssen for increased motility of the
gastrointestinal tract, was later withdrawn from the US market due to concerns of
fatalities linked to cardiac arrhythmias.
The product, however, continues to be exported from India to
countries like Switzerland, Thailand, Mexico, China and Canada.
Click here to view all the DMF submissions in Q4 2016 and Q1 2017 (Excel version available) for FREE!
Our view
The last quarter of 2016 and the first quarter of 2017 clearly
demonstrate an API industry in India and China, which is extremely active with
new product development, regardless of disappointing financial results posted
by major pharma companies and growing concerns over regulatory non-compliances.
Given the market headwinds and increased compliance expectations,
it remains to be seen how many of these DMFs filed actually result in drugs
reaching the market.
Click here to view all the DMF submissions in Q4 2016 and Q1 2017 (Excel version available) for FREE!
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