Re: Synta says drug (in combination with chemos) delays worsening of melanoma

J wrote:

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http://uk.reuters.com/article/governmentFilingsNews/idUKL2690074520070926

Synta says drug delays worsening of skin cancer
Wed Sep 26, 2007 3:43pm BST

By Michael Kahn

BARCELONA, Sept 26 (Reuters) - An experimental drug that spurs cancer
cells to commit suicide helped melanoma patients live longer and delayed
worsening of their disease, the drug's maker said on Wednesday.

Patients with skin cancer that had spread to other parts of the body lived
four months longer when using the drug -- called STA-4783 -- in
combination with the standard chemotherapy treatment paclitaxel, said
Anthony Williams, vice president of clinical research at Synta
Pharmaceuticals (SNTA.O: Quote, Profile, Research).

And the cocktail more than doubled how long patients survived without
their cancer getting worse, he told the European Cancer Conference.

Alexander Eggermont, incoming president of the European Cancer
Organisation and who was not involved in the study, said the way the trial
was done and the results merit further research.

"It is a novel mechanism," he said. "If you have these results, you have a
green light to do a Phase III trial." Phase III is the final stage of
human testing before a drug can win licensing approval.

Melanoma is an aggressive, difficult to treat cancer with an average
survival rate of about six months for people with advanced the stages of
the disease. Current therapies have only a limited impact or are highly
toxic.

The new treatment centres on unstable charged molecules called free
radicals that can damage the body and which people often try to get rid of
by consuming food or drink rich in anti-oxidants such as vitamin E.

But Synta found that increasing the level of free radicals in melanoma
patients using the drug caused the tumour cells to kill themselves without
impacting normal cells,

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http://www.boston.com/news/globe/health_science/articles/2007/07/16/from_industry_castoff_to_potential_medicine/

From industry castoff to potential medicine
Scientists turn to old chemicals for cure for melanoma, other cancers
By Robert Cooke, Globe Correspondent | July 16, 2007

By poking through thousands of industrial chemicals, scientists report that they have
found a new drug that, for the first time, improves the grim outlook for patients with
the most dangerous form of skin cancer.

Although the research and clinical trials are still in early stages, preliminary data
suggest that the new drug, called STA-4783, doubles patients' survival time to 12
months, with very few side effects, said Safi Bahcall, president and chief executive of
Synta Pharmaceuticals, a small biotechnology firm in Lexington that developed the drug.
His company recently announced the results at the annual meeting of the American Society
for Clinical Oncology in Chicago.

"It's the first time anyone has seen a drug that extends the survival time of people
with metastatic melanoma," Bahcall said. "Normally, half of the people who come in with
malignant melanoma are dead in six months."

"The key thing will be to validate these early, significant results," said Dr. John
Kirkwood, a leading melanoma specialist at the University of Pittsburgh Cancer
Institute.

"We are encouraged with the pilot results with this new agent," he said, adding that
further testing, on a larger scale, is required.

STA-4783's anticancer properties were uncovered by a drug-screening program in which
Synta scientists are carefully testing chemicals one by one to assess their medical
potential.

The company has several other drug candidates derived from industrial chemicals in the
research pipeline, including a possible drug for arthritis, a newer oral version of
STA-4783, a second oral drug for cancer, an antipsoriasis skin drug, and an inhibitor of
autoimmune diseases.

All these came from Synta's focus on small-molecule compounds that exhibit unexpected
and unexplored medical properties. Hundreds of thousands of such chemicals exist,
originally made for industrial purposes, but they are rarely studied for medical
potential.

In the past, of course, some industrial chemicals were discovered, often by accident, to
have medical uses.

Mustard gas, for example, which is notorious as a frightful chemical warfare agent
during World War I, opened the door to modern chemotherapy for childhood leukemia. Bayer
AG in Germany became a major pharmaceutical supplier after discovering medical uses for
its industrial chemicals.

Lan Bo Chen, an emeritus professor of pathology at the Dana- Farber Cancer Institute in
Boston, came up with the idea in 1979 of searching through industrial chemicals,
particularly photographic dyes, for cancer treatments.

One early dye, rhodamine 123, for instance, was found to selectively seek out and damage
the energy factories within cancerous cells, killing them while leaving healthy cells
untouched. (It was later abandoned because it wasn't potent enough.)

STA-4783 appears to work in much the same way, causing cancer cells to self-destruct,
while leaving normal ones unscathed.

The new research findings come from a Phase II clinical trial of 81 patients at 21
medical centers, who were given STA-4783 along with a version of the standard cancer
drug, Taxol. The encouraging results prompted the US Food and Drug Administration to
grant STA-4783 fast-track status last November to speed up the review process.

A far larger trial, enrolling 600 patients at 150 hospitals in 15 countries, is now
getting under way, Bahcall said, and results are expected in late 2008.

Synta found STA-4783 from among a stockpile of chemicals from Russia, bought with money
donated by junk-bond guru Michael Milken, a cancer survivor who is supporting two drug
development programs involving Synta with a gift of $10 million.

If the drug is proven safe and effective, it would offer the first real hope for
advanced melanoma patients, whose tumors are now considered essentially unstoppable.

Most of the 60,000 new melanoma cases seen annually in the United States are treated
successfully with surgery, but about 8,200 patients per year don't spot the disease
early enough, and only 16 percent of them are expected to survive at least five years.

Chen believes there are many more drugs waiting to be discovered in chemical stockpiles.

"The chemical libraries are gold mines, but they're all sitting in warehouses at the
moment," said Chen, because winning permission to test them "is virtually impossible
right now."

Companies are leery of participating in drug development research because it is very
expensive, time-consuming, highly uncertain, and fraught with legal hazards.

Kodak, for instance, made its chemicals available to Chen in earlier days, but not
anymore.

"Kodak exited the pharmaceuticals business in 1994 and subsequently has not pursued
further follow-up on this earlier work," said company spokesman Christopher K. Veronda.
"Since a representative sample of the chemical library was already screened, it's
unlikely there are undiscovered compounds that may have therapeutic value."

But Chen disagrees.

"I think these companies should have a sense of social responsibility and allow
scientists to study their precious compounds," he added. "They were synthesized over
many decades by gifted chemists, at the expense of hundreds of millions of dollars, yet
we let it sit in the warehouse."


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