[Ip-health] WSJ: Drugs for Inherited Cancers Get Fresh Push

Thiru Balasubramaniam thiru at keionline.org
Mon Sep 16 06:15:17 PDT 2013


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<SNIP>

BRCA mutations still account for only a fraction of total cancers, so the
potential market is relatively narrow. Roughly 15% of ovarian cancer cases
involve patients who are BRCA-positive, while the rate is as high as 10% in
breast cancer, according to the National Cancer Institute.

By pinpointing eligible patients through genetic screening, companies are
betting they can prove a more definitive benefit, helping make the case for
premium pricing. Citigroup projects that the drugs would be sold for
between $12,500 and $15,000 per month.


http://online.wsj.com/article/SB10001424127887323864604579068913264399616.html

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   - September 15, 2013, 9:37 p.m. ET
   Drugs for Inherited Cancers Get Fresh PushAfter Earlier Disappointments,
   Treatments Are Seen Helping Patients With Breast-Gene Mutation





   By
   - JOSEPH WALKER

Drug makers are rallying to a class of drugs that, if they succeed, could
be the first treatments to target breast and ovarian cancers tied to the
genetic mutations known as BRCA 1 and BRCA 2.

Two years ago, the drugs were all but written off after a string of
clinical study failures in broader cancer-patient populations. But later
research and a closer examination of existing data showed the drugs, known
as PARP inhibitors, had a pronounced effect in BRCA patients

As many as one in 400 individuals carry an inherited BRCA mutation, which
significantly raises the risk of breast and ovarian cancer. And while
advances in genomics have led to several drugs targeting genetic variants
in tumors, there is still no treatment specifically for BRCA mutations.

In June, researchers presented positive data on
AstraZeneca<http://online.wsj.com/public/quotes/main.html?type=djn&symbol=AZN.LN>
PLC's
drug olaparib, the most developmentally advanced among the class. Adding
olaparib after chemotherapy helped ovarian cancer patients with BRCA
mutations to live a median of 11.2 months without their cancers growing
worse, or 6.9 months longer than study subjects taking placebos in the
mid-stage trial. AstraZeneca said it is weighing an early filing for
regulatory approval in Europe, which
Citigroup<http://online.wsj.com/public/quotes/main.html?type=djn&symbol=C>
says
could lead to approval next year.

BioMarin Pharmaceutical<http://online.wsj.com/public/quotes/main.html?type=djn&symbol=BMRN>
 Inc., Clovis Oncology<http://online.wsj.com/public/quotes/main.html?type=djn&symbol=CLVS>
 Inc.and Tesaro<http://online.wsj.com/public/quotes/main.html?type=djn&symbol=TSRO>
Inc.  also
presented evidence of their drugs' activity in shrinking tumors at the June
meeting of the American Society of Clinical Oncology. Though the drugs are
early in their development and could still fail, the companies are
beginning late-stage trials this year that could lead to U.S. approvals in
2017, according to Citigroup. AbbVie Inc., which is also developing a PARP
inhibitor, said it is "likely" to start late-stage studies in the next six
to 12 months.

BRCA mutations still account for only a fraction of total cancers, so the
potential market is relatively narrow. Roughly 15% of ovarian cancer cases
involve patients who are BRCA-positive, while the rate is as high as 10% in
breast cancer, according to the National Cancer Institute.

By pinpointing eligible patients through genetic screening, companies are
betting they can prove a more definitive benefit, helping make the case for
premium pricing. Citigroup projects that the drugs would be sold for
between $12,500 and $15,000 per month.

"If we can specifically target the patient, there's going to be a better
benefit and people are willing to pay more," said Tesaro President and
Chief Scientific Officer Mary Lynne Hedley.

In ovarian cancer, the drugs could be one of the biggest advancements since
the development of platinum-based chemotherapy in the 1970s, which is now
the standard of care, said Jonathan A. Ledermann, professor of medical
oncology at the University College London Cancer Institute. Some companies
are also testing the drugs in non-BRCA patients in hopes that additional
genetic mutations or biomarkers will be identified and expand the overall
market.

"PARP inhibitors are simple oral medications that are well-tolerated and
have the ability to give long-term benefit" to patients, said Dr.
Ledermann, who was principal investigator in the AstraZeneca study.

The drugs work to prevent cancer cells from repairing themselves after
being damaged with chemotherapy by stalling production of an enzyme called
poly ADP-ribose polymerase, or PARP, that is responsible for DNA-repair.
PARP inhibitors are thought to work with BRCA mutations, in particular,
because the mutations also interfere with the DNA-repair process,
increasing the chances of destroying the cancer cells.

That PARP inhibitors are once again a focus of the pharmaceutical industry
underscores how growing knowledge about the molecular underpinnings of
cancer can make successes out of drugs that fail in broader populations.

Not long ago, researchers believed the drugs could work in a broader cancer
patient population and reach as much as $5 billion in annual sales in
breast cancer alone, according to Yaron Warber, a Citigroup analyst.

A drug being developed by Sanofi SA—called iniparib—cast a cloud over the
class when the company said in January 2011 that a late-stage study had
failed.

Later that year, AstraZeneca said it wouldn't advance development of
olaparib for a broader ovarian cancer population after regulators indicated
that the drug's benefit during a midstage trial wouldn't be enough for
approval.

The string of disappointments nearly sank development of the treatments, as
new clinical trials stalled and pharmaceutical giants
Pfizer<http://online.wsj.com/public/quotes/main.html?type=djn&symbol=PFE>
 Inc. PFE +0.70%<http://online.wsj.com/public/quotes/main.html?type=djn&symbol=PFE?mod=inlineTicker>
and
Merck & Co. sold off rights to their own PARP inhibitors.

"Big pharma struggled with saying, is this a niche population or something
better?" says Jane Robertson, AstraZeneca's global executive director of
oncology.

The pessimism presented an opportunity for two biotech firms—Tesaro and
Denver-based Clovis Oncology—which bought the rights to Merck and Pfizer's
drugs, respectively. Deal terms weren't disclosed, but Tesaro's Ms. Hedley
said her company exploited uncertainty around PARP inhibitors to enter the
niche cancer drug area.

Ultimately, the effect in BRCA patients has become clearer. Using archived
blood and tumor tissue samples of patients in the disappointing midstage
trial, AstraZeneca was able to determine that over half were BRCA-positive
and a subsequent analysis led to the positive study results presented this
summer.

BioMarin Chief Executive Jean-Jacques Bienaimé says the renewed interest in
PARP inhibitors reflected the growing embrace of niche cancer drugs that
command high prices.

"I think those days of getting responses from 40% of patients and giving
60% of patients side effects that they don't' need are over," Mr. Bienaimé
says. "What we're doing is the future and I don't see how that's going to
change."

*Write to *Joseph Walker at joseph.walker at dowjones.com



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