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Print Edition StoriesFriday, October 23, 2009
Synta's failed drug target may be reborn from biomarker discovery
By Julie M. Donnelly
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In February, CEO Safi Bahcall and the team at Synta Pharmaceuticals got some terrible news. The company’s promising Phase 2 drug trial for a therapy targeting metastatic melanoma had to be halted immediately. Elesclomol, as it’s called, appeared to be killing people.
“It was an extremely sad day. It was painful,” Bahcall said.
But eight months later, the drug target may be resurrected to treat a subset of patients.
“It was a huge surprise and the team was excited. A lot of people looked around and said, ‘We have a drug,’ ” Bahcall said.
The drug is getting a new life because researchers discovered that while Elesclomol was only hurting patients with high levels of an enzyme called lactate dehydrogenas, it was helping patients with normal levels.
Cancer researchers have long known that a high level of LDH is a negative prognostic — a bad sign for a cancer patient’s chances of survival. But this discovery puts a very sharp tip on this point.
Not only did patients with high LDH levels not respond to the drug, it made them sicker than no drug at all. Synta researchers say this discovery turns a mere prognostic into a predictor, also known as a biomarker, that will determine who gets the drug, and who doesn’t.
The commercialization of drugs tailored to biomarkers has led to better treatment of patients, decreased cost to the health care system and billions of dollars in revenue for companies that sell the drugs connected to the biomarkers. Drugs tied to biomarkers often have an easier time passing muster with private and public payers.
“The government is getting much more sophisticated about how it looks at the design of the clinical trials. They want to make sure the drug works in a certain population before they set a price point for reimbursement,” said Ravi Harapanhalli, principal consultant at Waltham-based Parexel Consulting.
To date, there have been four well-known biomarkers in cancer. The most famous is HER2, a protein that is over-expressed in about 25 percent of breast cancer patients. Herceptin, developed to counter the mutation, netted $1.4 billion in revenue last year. There also are identified biomarkers for leukemia, colon cancer and lung cancer that have led to blockbuster drugs. Most of these drugs first failed in trials aimed at the entire patient population for these diseases and had to start clinical trials focusing on a smaller patient group.
This will be Synta’s next step. First, the company has to wait for all the survival data to come in for the melanoma trial, and that is likely to take a year. Once the data is in, Synta plans to file with the U.S. Food and Drug Administration to start smaller, lower cost trials for Elesclomol. The trials would be for cancers other than metastatic melanoma and would include only patients with normal levels of the enzyme. Only after all of that, Bahcall said, would Synta think about restarting a melanoma trial.
A more personalized approach to drug discovery may eventually lead to fewer trial failures, and it may also potentially provide greater returns for investors. A particularly dramatic illustration of the power of a biomarker to drive investor confidence is Rockville, Md.-based Human Genome Sciences. The future of the company’s lupus drug candidate, Benlysta, looked dim after lackluster Phase 2 results.
But then a Phase 3 study, focused on a subset of lupus patients who tested positive for certain antibodies, proved successful in July. The company’s stock soared almost 400 percent and has kept up a steady climb since then.
Could Synta become the next Human Genome Sciences? There’s a long way to go, analysts say.
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