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Executive Summary

ROCHE's ddC TO CONTINUE EXPANDED ACCESS UNDER TREATMENT IND approved by FDA on May 31. The change from open label to Treatment IND was announced in a June 13 FDA "Talk Paper." Under the program, AIDS and advanced ARC patients who are intolerant to AZT (Burroughs Wellcome's Retrovir) or ddI (Bristol-Myers Squibb's Videx) will be eligible to receive ddC (Hivid). The treatment protocol will significantly reduce physicians' monitoring of patients and paperwork. As with ddI, the Treatment IND for ddC also replaces the requirement for approval by local institutional review boards with patient acceptance through the national IRB. Hoffmann-LaRoche said June 20 that it will be sending physicians letters within the next two weeks informing them of the new protocol. The company has not yet issued a press release notifying the public of the change from the open-label study to the Treatment IND. As of April 15, 2,800 patients had been enrolled in the open-label program. Under the Treatment IND, patient visits will be reduced to one per month for the first six months and every other month thereafter. Patient case report forms will be shortened from six pages every two weeks to two pages every four weeks. Eligible patients can now receive automatic approval from a national IRB instead of local IRBs, some of which took four to seven months to approve a patient. The new treatment protocol also eliminates certain tests, such as the p24 antigen test. The changes implemented by the Treatment IND appear to accede to demands previously made by the AIDS activist community. The AIDS activist group ACT UP was instrumental in organizing a several-month long boycott of Roche products in protest of the requirements for participation in the earlier expanded access program ("The Pink Sheet" March 18, T&G-6). In a letter to ACT UP, Roche outlined the changes that are being implemented by the treatment protocol and suggested that the group stop its "boycott activities." In addition to the Treatment IND, Roche is planning several other ways of smoothing relations with the AIDS activist community. The company is seeking an ombudsman to help resolve issues with ddC's expanded access program. Roche has included a timetable for the processing of patients' applications in the physician enrollment forms. Physicians also will receive quarterly toxicity reports with a breakdown by sex and race. In its letter, Roche also provided ACT UP with updates of results from the ddC clinical trials. "The early data suggest that in AIDS and advanced ARC patients with less than three months of prior AZT therapy, ddC may not be as efficacious as AZT during the first 24 weeks of treatment," Roche stated. However, the letter continues, "early data from a second study comparing ddC to AZT in patients with one year of prior AZT therapy suggests a trend towards ddC superiority, though it was not statistically significant." Roche summarized results from four clinical trials and the expanded access program. In (AIDS Clinical Trial Group) ACTG 114, the study of ddC versus AZT in AIDS and advanced ARC patients who had less than three months of prior AZT treatment, "no statistically significant differences in patient survival were shown between the two groups," Roche said. "There were, however, more AIDS defining opportunistic infections and neoplasms in the ddC group." The letter adds that for "patients who entered with CD4 counts greater than 100, the differences between the two groups were not statistically significant, although the trend still favored AZT." ACTG 119, a comparison of ddC and AZT in 102 AIDS and advanced ARC patients who had one year of prior AZT treatment, "shows a trend towards fewer [opportunistic infections] and neoplasms in the ddC group," the company noted. ACTG 106 and ACTG 047, in which ddC is given in combination with AZT either in an alternating schedule or concomitantly show that CD4 cell improvements are more pronounced than what is usually seen with AZT alone, and some regimens "showed a prolongation in this improvement beyond 48 weeks of treatment" (see T&G-10). In the expanded access program, out of "the first 833 patients entered, 25 (3%) have had to discontinue due to ddC toxicity, 13 (1.6%) due to [peripheral neuropathy] and 3 (.4%) due to pancreatitis." Other reasons for discontinuation were: "rash, chest pain with dyspnea and cough, oral ulcers and nausea," Roche said. In all of the studies through April 10, "there have been a total of 14 cases of pancreatitis or increased amylase." The firm added: "Seven of these were considered possibly or probably related to ddC and eight of the 14 had a prior history of pancreatitis or increased amylase before receiving ddC. Four of the seven that were considered possibly or probably related to ddC had a prior history."



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