Vertex Sees Liver Toxicity With Emerging Hep C Drug, Faces FDA Hold

Xconomy Boston — 

Vertex Pharmaceuticals suffered a meaningful setback today in its bid to remain a long-term player in the treatment of hepatitis C.

The Cambridge, MA-based biotech company (NASDAQ: VRTX) said today that the FDA has stopped the company from giving certain doses of its VX-135 drug candidate for hepatitis C in a mid-stage U.S. study, after seeing evidence of liver toxicity in patients in Europe. The FDA put a hold on Vertex’ plans to deliver 200-milligram doses of VX-135 in the U.S., but has allowed the study to continue enrolling patients on a lower, 100 milligram dose.

That decision was made after researchers saw liver toxicity in three of 10 European patients who got 400 milligrams of the Vertex drug, before they stopped enrolling patients in that group. The liver toxicity, measured in an increase in liver enzymes, was reversible once patients quit taking the drug, Vertex said. Vertex said that patients on the 100 and 200-milligram doses were able to tolerate the drug well, and none of those dropped out of 12-week study in Europe because of side effects.

“Developing safe and effective medicines for patients is our goal,” said Robert Kauffman, Vertex’s chief medical officer, in a statement. “We are committed to continuing to work closely with the FDA to provide the data needed to support evaluation of a 200 mg dose of VX-135 in the U.S.”

Vertex shares fell 11 percent, to $78 a share, in after-hours trading following the announcement.

The clinical hold is just the latest setback for Vertex in hepatitis C. Although the company blazed a new trail in the field by winning FDA approval in 2011 with its protease inhibitor telaprevir (Incivek), that treatment still must be given in combination with injectable interferon alpha, which causes flu-like side effects. Competitors such as Gilead Sciences (NASDAQ: GILD) and AbbVie (NYSE: ABBV) are both ahead in late-stage development with all-oral combination regimens that have increased hepatitis C cure rates without subjecting people to interferon. The results with competing drugs have been so compelling the past couple years that many hepatitis C patients have elected to wait until the new compounds are approved by the FDA instead of taking the currently available compound from Vertex.

VX-135, a nucleotide polymerase inhibitor, represents one of Vertex’s best chances to remain competitive in a landscape dominated by all-oral therapy. Vertex got the rights to this molecule through a collaboration with South San Francisco-based Alios Biopharma in 2011.

Vertex outlined a list of studies that remain ongoing with VX-135 in today’s statement. The drug is still being tested in combinations with compounds from Bristol-Myers Squibb and Johnson & Johnson, although Vertex said today that a VX-135 collaboration with GlaxoSmithKline ended last month.