[Ip-health] Blomberg: Indian Drugmakers Engineer Hep C Cocktails Impossible in West

Thiru Balasubramaniam thiru at keionline.org
Thu Oct 8 22:21:29 PDT 2015


Indian Drugmakers Engineer Hep C Cocktails Impossible in West

Ketaki Gokhale

Caroline Chen

October 9, 2015 —

New cocktails could help tackle hepatitis C in poor countries
Indian companies eyeing market for genotype 3 of hepatitis C

Drugmakers in India are hard at work engineering hepatitis C combination
pills impossible in western nations due to patent protections.

New antiviral medications from Gilead Sciences Inc. and Bristol-Myers
Squibb Co. have transformed the way hepatitis C is treated, making it a
curable disease. Treatment regimens combining Bristol-Myers’ Daklinza with
Gilead’s Sovaldi were approved by European authorities as effective against
most strains of the hepatitis C virus, but a combination pill can’t be
manufactured because the two companies haven’t collaborated on making one.

In 2001, before India started recognizing product patents, India’s Cipla
Ltd. revolutionized the treatment of HIV by making the first pill that
combined three different therapies, patented by three different western
drugmakers. Now, generic drugmakers in India are working on a one-pill
cocktail of the ingredients in Daklinza and Sovaldi that could compete with
blockbuster Gilead drugs.

“For sure, in India, it can happen,” said Dharmesh Shah, managing director
of Mumbai-based BDR Pharmaceuticals International Pvt., one of the Indian
companies in early stages of researching such a pill. “If one can
circumvent on the individual product patents, and with a proper regulatory
approval, for sure the combination can come in.”

Patent applications in India for Sovaldi, also known as sofosbuvir, and
Daklinza, also known as daclatasvir, are being challenged by groups of
patients, lawyers and scientists. Decisions on whether Indian patents will
be awarded to the two U.S. companies are pending. If they don’t win
patents, it would pave the way for Indian generics and combination pills.

India’s patent office has rejected patents for drugs including Novartis
AG’s cancer treatment Gleevec and Roche Holding AG’s HIV treatment Valcyte.
In 2012, an Indian patent appeals board revoked patent protection for
Roche’s hepatitis C injection Pegasys. The patent office didn’t answer
calls seeking comment.

Generic Licenses

If the patent challenges on the Gilead and Bristol-Myers drugs fail, Indian
companies would need to win licenses to copy the patented drugs and combine
them. Bristol-Myers is in advanced discussions with Indian drugmakers for
licenses to make and sell generic daclatasvir in 90 countries, spokesman
Rob Perry said via e-mail. The intended agreements would allow the
development of combination medicines if the licensee has rights to other
drugs, Perry wrote.

Gilead last year licensed 11 generic drugmakers including Hetero Labs Ltd.,
Cipla andAurobindo Pharma Ltd. to make and sell generic sofosbuvir in 101
developing countries. Those agreements also allow the development of
combination medicines with other companies’ drugs, Cara Miller, a Gilead
spokeswoman, wrote by e-mail. Spokespeople for Cipla, Hetero and Aurobindo
didn’t respond to e-mails seeking comment.

There are six common strains of hepatitis C. Genotype 1 is the most common
hepatitis C strain, accounting for 46 percent of cases. That’s followed by
genotype 3, which is more common in India and Southeast Asia and infects
almost a third of patients globally.

The European Commission in August last year approved Daklinza for use in
combination therapy across genotypes 1, 2, 3 and 4, which together account
for 94 percent of the world’s hepatitis C cases -- meaning that a combined
regimen could be effective in a wide swath of patients.

The World Health Organization in May put the Gilead and Bristol-Myers
treatments on its essential medicines list, which guides governments on
what drugs to make widely available.

“Evidence continues to accumulate that of the existing regimens, sofosbuvir
+ daclatasvir provides the broadest genotypic coverage,” wrote Stefan
Wiktor, leader of WHO’s Global Hepatitis Program in Geneva, in an e-mail,
referring to Sovaldi and Daklinza by their generic names. Because the
combination works across different strains of the hepatitis C virus it is
well-suited to low-income countries where genotype testing isn’t available,
he said.

Simplify Distribution

Combination therapy is key for HIV, malaria and tuberculosis, as well as
chronic conditions like diabetes because it improves patient adherence,
according to the WHO. Such pills also simplify distribution, making them
useful to poor countries. Also, thecost of a fixed-dose combination pill
can be less than that of the separate products.

Founded in 2003, BDR supplies low-priced generic versions of expensive
drugs and bulk ingredients in India and other developing countries. To
decide whether to pursue the hepatitis C combination product, Shah is
closely watching for decisions from the Indian patent office. BDR isn’t
licensed to make either drug at this time. The first regulatory filings by
Indian companies for the combo pill “should happen in the very near
future,” Shah said.

Making a new fixed dose combination requires tests to prove it is
chemically stable, studies to show ingredients work the same way as the
original drug, and possibly also human trials if Indian regulators ask for

Genotype 3

Gilead’s own blockbuster combo pill, Harvoni, combines sofosbuvir and
another drug it developed. Harvoni, approved last year by the U.S. Food and
Drug Administration for genotype 1, was Gilead’s best-selling medicine in
the quarter ended June with sales of $3.6 billion.

The FDA approved daclatasvir for use in combination with Sovaldi to treat
genotype 3 infections in July. The combination is also being reviewed on a
priority basis by the FDA to treat patients co-infected with HIV, advanced
cirrhosis of the liver and post-transplant patients.

Gilead and Bristol-Myers didn’t hold late-stage trials of the combination,
however, because Gilead decided to pursue Harvoni, which combined its own
drugs, believing it could bring it to market faster than a medicine
requiring inter-company collaboration. After Gilead’s Sovaldi was approved
by regulators, Bristol-Myers did late-stage human trials of its drug in
combination regimens with Sovaldi to secure approvals in the U.S. and

New Combinations

Gilead is also working on a new experimental drug combination that showed
high cure rates across multiple hepatitis C strains in four final stage
trials. Gilead spokeswoman Cara Miller in an e-mailed response to questions
said it will file that combination with U.S. regulators by the end of the
year, then apply for inclusion on the WHO essential medicine list and work
as quickly as possible to register it in developing countries.

Gilead’s license agreements allowing Indian generic drugmakers to make and
sell generic Sovaldi also give them the rights to make the experimental
combination pill it is studying now.

In Bangladesh, which isn’t required under a World Trade Organization
agreement to recognize pharmaceutical patents, Incepta Pharmaceuticals Ltd.
is interested in developing a generic of Gilead’s experimental combination,
as well as a generic pill combining sofosbuvir and daclatasvir, said Ehsan
Aziz, general manager of marketing, in an e-mail.

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