BioWorld International Correspondent

LONDON - Ark Therapeutics Group plc has backed off from moving Vitor, its treatment for cancer cachexia, into a full-scale Phase III trial after talks with the FDA. The company instead is opting to carry out a 60-patient pilot to gather further intelligence on endpoints and consider the design of the definitive 250 patient Phase III study.

The London-based company said the change is in response to the FDA's increasingly rigorous stance on clinically relevant endpoints and safety data. "We want to make sure the story is one the FDA is happy to sign up to," Martyn Williams CFO, told BioWorld International.

The decision pushes back development by nine months, some of which time the company hopes to make up by a faster processing of the eventual file. Vitor has fast-track designation. Williams said the decision to do a further trial does not negate that status, as the file still will get an expedited review.

As an angiotensin-converting enzyme (ACE) inhibitor currently marketed for the treatment of hypertension, Vitor has a well-understood safety and side effect profile. At issue is what clinical endpoints to choose for the Phase III study. Apart from reduction in weight loss, maintenance of grip strength and assessment of fatigue levels, some new potential endpoints have emerged since the design of the Phase II/III trial that reported in January 2006.

"There are a number of ways of measuring efficacy," Williams said. "Some have come about recently, and we want to make sure we plumb for the correct ones."

Ark's caution is inspired in part by the FDA's recent rejection of Vernalis plc's Frovatriptan in the treatment of menstrual migraine. Like Vitor, it is a marketed product with a known safety and side effect profile, but the FDA refused the label extension, questioning if the positive data were "clinically meaningful."

"The FDA's decision on Vernalis and Frovatriptan shocked everyone," Williams said. "[The pilot trial] is about making sure we get it right with Phase III."

Vitor increases the ability of mitochondria to produce energy, and prevents both the breakdown of the muscle proteins actin and myosin, and the reduction in production of these proteins, that is prompted by cytokines released by tumors.

The earlier Phase II/III trial in colorectal, pancreatic and non-small-cell lung cancer did not reach significance. Treated patients on average lost 29 percent less weight, but pancreatic cancer patients showed a much lower response. In addition, 42 percent of patients did not complete the study, causing high variability in the data.

While patients had lost an average of 24 pounds, or 15 percent of body weight in the six months before entering the study, that rate of weight loss slowed markedly in both treated and untreated groups at the start of the study. To avoid this 'study effect,' the pilot will have lead in.