A pivotal Phase III trial of a treatment for genital warts attained aresponse rate of 77 percent, as reported in Vienna, Austria yesterday tothe 24th Annual Meeting of the European Society for DermatologicalResearch.Elaine Orenberg, director of technical services at MatrixPharmaceutical Inc., of Menlo Park, Calif., presented the trial results ina poster titled "Intralesional AccuSite (Fluorouracil/ Epinephrine)Injectable Gel for Treatment of Condylomata Acuminata: A Phase IIIclinical Study."Genital warts (Condylomata acuminata) are among the fastest-growingsexually transmitted diseases in the Western world today. The soft,itchy, pinkish-red, highly contagious growths erupt in multiplenumbers on the genital organs of sexually active men and women, aswell as on adjacent anal tissue.Matrix's randomized, double-blind, placebo-controlled study testedsafety and efficacy of its treatment on 359 male and female patients at34 U.S. medical sites in 18 states, plus the District of Columbia. Thesubjects had a total of 1,926 warts, ranging in combined area perpatient from one to 436 square millimetersThe sustained-release AccuSite chemotherapy package consists of threecomponents: a biodegradable protein carrier matrix, bovine collagen,which delivers 5-fluouracil (5-FU) to the base of each lesion via a 30-gauge ("pin-prick") needle, together with a dose of epinephrine. Thispotent vasoconstrictor acts as a "chemical tourniquet," explainedMatrix President and CEO Craig McMullen."The gel formulation," the poster explained, "retains high localconcentrations of 5-FU at the diseased site for extended periods."Analysts Wired In To Genital Wart ResultsThe Phase III trial divided its patient population into three cohorts: 5-FU, plus and minus epinephrine, and placebo. The combination of bothdrugs, the poster reported, ". . . produces a statistically significantlybetter complete response rate than the gel formulation withoutepinephrine . . ."Speaking from Vienna yesterday, McMullen told a transatlanticconference call with financial analysts that "The data reported here willsupport our first new drug application, which we expect to file in thefirst quarter of 1995." Matrix will market AccuSite for genital wartsjointly with its strategic ally, Medeva plc, of London. (See BioWorldToday, May 20, 1993, p. 1.)In projecting the commercial potential for Matrix's condylomatachemotherapy, McMullen cited "more than eight million office visits todoctors in the U.S." last year for treatment of genital warts.Epinephrine is commonly administered to contain asthmatic attacks; 5-FU is a widely used anti-cancer drug, which acts on fast-dividing cellsby interfering with their synthesis of DNA and RNA. Uracil is one ofthe four nucleotide bases in RNA; fluouracil replaces one of itshydrogens with a fluorine atom.Condylomata acuminata is a benign, rather than a malignant, growth,caused by the human papilloma virus. In the past 10 years, its incidencehas increased at about 10 percent annually, twice that of genital herpes.In the U.S., an estimated three million patients a year are diagnosedwith genital warts.Complicating therapy is the tendency of the virus to lie latent for up tohalf a year, before declaring itself with an infective outburst of severalpapilloma-laden warts at once.The most promising treatment for genital warts to come down the pikein recent years is injectable alpha interferon. This promise, McMullentold the analysts, "is limited by interferon's inability to clear up morethan a few of a patient's lesions, responses "in the low 40 percents,"and systemic reactions causing flu-like symptoms."He said that "AccuSite has the highest response rate of any productavailable today."Andrew Korey, Matrix's vice-president of medical and regulatoryaffairs, speaking from Menlo Park, told the teleconference listeners thatMatrix's AccuSite therapy, administered as an out-patient procedureduring the clinical trial, had incurred "no clinically significant systemicreactions or adverse medical events." He explained that local side-effects, notably erythema and desquamation, were incidental to theactual falling off of successfully treated warts.In a press release announcing its Phase III results, the company warnedthat genital wart is "a major public health concern because of itsassociation with . . . cervical and genital cancers." The statement notedthat "the wart virus can also cause infection in the throat of babies bornto women with genital warts."Fielding a question from analyst Robert Peterson, of Henifen ImhoffInc. in Denver, as to why the trial evaluated 280 males but only 79females, McMullen explained that the company's system depends oninjection of external lesions. "Two-thirds of gynecological genitalwarts are internal, so untreatable by our present technology." ButMatrix is working on the problem, he added.AccuSite's Phase III trial reported that the treatment group, which hadfrom one to 20 condylomata each, experienced a 77 percent completeresponse rate on a per-lesion basis, and 89 percent for combinedcomplete and partial responses.No New Money On Horizon _ YetOn a per-patient basis, all warts cleared up in 61 percent of thosetreated, compared with 5 percent for placebo recipients. And of lesionsresponding completely, 61 percent maintained this result for the entirethree-month follow-up period.Dermatologist James Swinehart, a private practitioner in Denver, is oneof the 34 clinicians who took part in the Phase III trial. He toldBioWorld Today: "We've done studies [of AccuSite] with warts, andwith squamous-cell and basal-cell carcinoma. All three, I think, haveworked pretty well. This was a blinded trial," Swinehart added, "so weof course didn't know who got what. But I think it's excellent, and thepatients like it a lot because it avoids the need for surgery."BioWorld Today asked Matrix's vice-president and chief financialofficer, Ronald Edinger, whether the company's teleconference withfinancial analysts presaged an early return to the investment capitalwell."The honest answer is," Edinger replied, "I really don't know. We needto look at the market, let this information settle into our stock price."Like all companies of our type," he added, "we are always mindful ofthe need to raise capital. We don't have specific plans today -- but thatmay change in an afternoon."Matrix (NASDAQ:MATX) stock closed unchanged Monday at $15.25per share. n
-- David N. Leff Science Editor
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