BioWorld International Correspondent

LONDON - With about one-third of subjects showing hair regrowth, the botanicals company Phytopharm plc might reasonably have expected to get a positive result in a Phase II trial of P45 in the treatment of male pattern baldness. The problem was, the majority of responders had been slapping the placebo cream on their pates every day for a year.

"It's staggering, really; completely crazy. There's no way you'd expect to get a 40 percent placebo effect," CEO Richard Dixey told BioWorld International.

He had a similar view on the effect the failed trial had on the company's stock price. Shares in Phytopharm fell by £1.32 to £7.30 when the news was released last Thursday. "It is not good news by any means, but the reaction on the stock market was completely overdone. A week earlier we announced we were ready to seek a partner for cancer chemoprevention, which is far more significant for us, and the share price didn't move."

The study in male pattern baldness (alopecia androgenica) was a randomized, double-blind, placebo-controlled study conducted at three UK centers. Seventy-five subjects applied either P45 or an inert placebo cream to the bald areas of their scalps once daily for 52 weeks. They attended the clinic for assessment after one month and every two months thereafter. Thirteen subjects in the P45 group, and 11 in the placebo group, completed the study.

Data from 69 subjects were analyzed, carrying forward the last score for those who dropped out. The investigators judged that 29 percent of the P45 group had hair regrowth; however, 38 percent of the placebo group also had a positive response. The subjects' own assessments were the same for each group, with 21 percent saying they thought the cream had worked.

Male pattern baldness has been studied in two previously reported double-blind trials. A Phase III study on Finasteride, a Merck compound, reported an increase in mean hair density of 11 percent in the treatment group, compared with a loss of 2.7 percent in placebo, after one year of treatment in 1,533 subjects. A study of Minoxidil (Pharmacia) in 36 men reported a 30 percent increase in hair mass in the treatment group over 96 weeks, compared with an 8 percent loss in the placebo group.

"A positive placebo response has not been reported in previous clinical trials of this condition. I think the large placebo response reflects a huge enthusiasm for herbal remedies two years ago when the trial began," said Dixey.

Phytopharm, based in Godmanchester, Cambridgeshire, is conducting a second Phase II trial of P45 in the treatment of alopecia areata and alopecia totalis, both of which are autoimmune forms of the disease. "We are going to wait for the results of this study before deciding what to do with P45," he said. "One thing we take forward from the alopecia androgenica trial is that there are no safety concerns."