Mesothelioma Drug VS-6063 Clinical Trial Stopped

Not every promising mesothelioma treatment drug in development lives up to its promise. In late September the maker of one such mesothelioma therapy shelved the drug for that very reason.

The mesothelioma drug is VS-6063. It was in the middle of a phase 2 clinical trial when Verastem, Inc., the mesothelioma drug maker, decided to initiate an orderly shutdown of the testing.

This decision came after the discovery that 372 mesothelioma patients taking VS-6063 showed no statistically significant improvement compared to mesothelioma patients taking a placebo.

After talking things over with the U.S. Food and Drug Administration (FDA) Data Safety Monitoring Board, Verastem officials realized that it was futile to continue the clinical trial.

The mesothelioma drug was safe, the FDA agreed. It’s just that it wasn’t effective enough to merit further study.

Not Inhibiting Mesothelioma Stem Cells Enough

This was disappointing news to everyone involved. What made the news such a bitter pill to swallow was that VS-6063 showed great potential in its earliest stages of testing.

Company officials said VS-6063 in the lab caused mesothelioma tumors to dramatically shrink after about 14 days.

The medicinal name of VS-6063 is defactinib. During human testing, it was given to patients orally. The drug was designed to be started right after patients completed mesothelioma chemotherapy.

VS-6063 was engineered to hunt for stem cells from which new mesothelioma cells could be spawned. Upon finding them, VS-6063 was supposed to wreak havoc by inhibiting stem cells from producing focal adhesion kinase.

The failure of VS-6063 to live up to expectations calls into question the future of a second inhibitor drug that Verastem has also been working on — VS-5584, which is not as far along in development as VS-6063.

Like VS-6063, VS-5584 has been the subject of much encouraging talk. It too is designed to lay siege to mesothelioma stem cells, but hitting them from a different flank. So, instead of focal adhesion kinase, VS-5584 inhibits production of enzymes mTORC1/2 and PI3K.

Earlier, Verastem began investigating the potential of having patients take VS-5584 and VS-6063 together. The idea is to create a synergy out of the drug combo. No word on how the halting of the VS-6063 clinical trial will affect studies into this pairing.

Other Mesothelioma Drugs Still in Pipeline

One reason the failure of VS-6063 calls into question the future of VS-5584 is that it caused the company’s stock price to collapse.

After announcing it would pull the plug on the phase 2 clinical trial of VS-6063, Verastem lost roughly two-thirds of its value on Wall Street.

The decline was so steep that it had investment analysts questioning whether Verastem could even survive. If Verastem goes out of business, that could be the end of VS-5584 — unless Verastem sells the rights to VS-5584 to another company.

Analysts speculated that, even if the company hangs on, other drugs in Verastem’s development pipeline may have a much harder time reaching the market.

Meanwhile, the chief executive officer of Verastem said his company is unshaken and remains committed to developing treatments for mesothelioma stem cells.

“We are disappointed with the [clinical trial] outcome, but we are deeply grateful for the support and commitment from the patients participating in the study, their families and the study investigators,” said CEO Robert Forrester.

Lou Vaickus, M.D., F.A.C.P., is Verastem’s interim chief medical officer. He said this: “[T]he use of single agent VS-6063 as a maintenance treatment following chemotherapy where all patients had residual disease was not sufficient.

“There remains a significant unmet medical need for new treatment options for patients suffering from this very complex, difficult-to-treat cancer.”

Verastem launched in 2010. It was co-founded by a venture capitalist and an MIT biology professor. Their goal was to develop drugs that would knock out cancer-regenerating stem cells. The company went public in 2012 and immediately raised $55 million.