Celgene Corp. today begins enrolling AIDS patients whosuffer from cachexia, a form of wasting, in its expandedaccess program for Synovir (thalidomide).

Celgene officials said they are optimistic about thewidening use of Synovir which they see as a link to thedevelopment of anti-inflammatory biotech drugs.

The expanded access program was approved by theFDA's Division of Anti-Viral Drug Products, locatedwithin the Center for Drug Evaluation and Research, onMonday under an open label, compassionate use protocol.

The new program complements Celgene's placebo-controlled double-blind Phase II clinical trial of Synovirwhich also is testing its efficacy in inducing weight gainin patients suffering from AIDS wasting. The open accessprogram has broader enrollment criteria than the clinicaltrial and will accept patients who also have otherconditions such as opportunistic infections, neoplasms,diarrhea and cirrhosis, said Celgene president and chiefoperating officer, Sol Barer. Also, patients who havefinished the Phase II clinical trial or are more than onehour away from a treatment center also are eligible toenroll in the expanded access program.

While the clinical trial is testing dosages of 100 mg and200 mg, the open access program will randomize patientsto 50 mg or 200 mg doses of Synovir. Initial response tothe therapy will be assessed at four weeks. Patients whofail to improve on the low dose can convert to the higherlevels. Celgene, based in Warren, N.J., said patients maycontinue therapy indefinitely.

Barer said the open access program was a "positiveindication that the drug is moving forward. We are in themidst of discussions with the FDA about convertingSynovir Phase II clinical studies to a pivotal trial," he toldBioWorld Today.

Only two drugs are currently available to treat wasting.Megace, formerly used to treat women with breast cancer,has been associated with some weight gain. Humangrowth hormone, now in Phase III clinical trials, also hasbeen used to treat cachexia. But human growth hormoneis far costlier than Synovir. Its manufacturers charge theFDA $11,000 for each three-month course of treatment,said Barer.

Celgene has applied to the FDA for cost recovery in theuse of Synovir in the expanded access program. Detailsabout what costs will be covered by the FDA will bemade public later, said Barer.

The FDA approved Celgene's inclusion of womencapable of bearing children in the expanded accessprogram to collect information about the differingphysiological response of women to the drug and possibleharmful effects on their reproductive capacity. Womenparticipating in the expanded access program must agreeto practice both barrier and oral steroids contraception.

Celgene sees its testing of Synovir as a "link to theimmune system," said Barer. "Synovir theoretically canmodulate the levels of TNFalpha," (tumor necrosis factoralpha), the hormone-like protein thought to causeautoimmune disorders and immunological conditionssuch as lupus, rheumatoid arthritis, inflammatory boweldisease and graft-versus-host (GVH) disease in organtransplant recipients.

Celgene is testing Synovir's ability to reduce the body'santi-inflammatory response in other conditions. Inaddition to the Phase II clinical trial involving AIDSpatients with cachexia, the product is involved in pilotstudies to measure its efficacy in reducing the effects ofcachexia in cancer and rheumatoid arthritis patients.

"Celgene's hurdle is to isolate the teratogeniccomponents of thalidomide from its anti-TNFalphaproperties," said Matthew Tarosky, thalidomide projectmanager in the FDA's Division of Anti-Viral DrugProducts.

Celgene scientists expect the Synovir clinical studies willenhance development of a new class of relatedcompounds that are even more efficacious in reducing thebody's anti-inflammatory response. These anti-TNFalphacompounds will be "more potent versions of the parentcompound," said Barer.

Animal studies of the anti-TNFalpha drugs already havebegun. Johns Hopkins University is operating apreclinical trial in patients with GVH. Celgene expects totake the anti-TNFalpha drugs to the investigational stagein 1996, Barer said. n

-- Michele L. Robinson Washington Editor

(c) 1997 American Health Consultants. All rights reserved.