Biochem Pharma - 3TC Pediatric Clinical Endpoint Study Shows That 3TC in Combination With Retrovir Significantly Reduces the Risk of Disease Progression and Improves Survival in Children.

LAVAL, QUEBEC--(BUSINESS WIRE)--June 27, 1997-- BIOCHEM PHARMA (ME, TSE BCH., NASDAQ BCHXF) BioChem Pharma Inc. announced today that a large U.S. study of children with symptomatic HIV disease has been stopped because an analysis of the data revealed that patients treated with 3TC(R)/Epivir(TM) (lamivudine) and Retrovir(TM) (zidovudine; AZT) had a 70 percent decrease in the risk of clinical disease progression compared to patients who received the drug didanosine (ddI). Survival was also significantly better in children receiving the 3TC+Retrovir combination therapy than those receiving ddI monotherapy. The study was conducted by the Pediatric AIDS Clinical Trials Group of the U.S. National Institutes of Health (NIH) and is known as ACTG study 300. These are the first data to demonstrate the superior clinical efficacy of combination drug therapy versus monotherapy in pediatric patients.

"These data show that 3TC and Retrovir in combination are effective and well-tolerated in children with HIV disease, as demonstrated by a reduction of disease progression, decreased rate of mortality and better overall growth," said Dr. Gervais Dionne, Executive Vice President, Research and Development, BioChem Pharma. "We are pleased that the positive results we have seen previously in adults treated with antiretroviral combination regimens which include 3TC have also been achieved with the use of 3TC and Retrovir in this important patient population."

The ACTG 300 study was initiated in July, 1995, and compared 3TC+Retrovir to ddI monotherapy and the combination of ddI+Retrovir in previously untreated, HIV-infected infants and children ranging from 42 days to 15 years of age. In February, 1996, results of ACTG study 152 showed that ddI monotherapy was superior to monotherapy with Retrovir and comparable to the combination of ddI+Retrovir. Therefore, the ACTG 300 trial was amended at that point to focus on the comparison of 3TC+Retrovir to ddI alone and to terminate further enrollment into the ddI+Retrovir arm. Patients previously randomized to the ddI+Retrovir arm continued to be followed under blinded conditions.

At a review of ACTG 300 on June 18, 1997 by an independent NIH Data Safety and Monitoring Board (DSMB), data were evaluated on 596 patients (236 receiving 3TC+Retrovir; 235 receiving ddI alone; 125 receiving ddI+Retrovir -- as randomized prior to the announcement of ACTG 152). In addition to showing an approximate 70 percent reduction in the risk of disease progression compared to ddI alone (15/236 in the 3TC+Retrovir group had disease progression compared to 38/235 in the ddI monotherapy group), the 3TC+Retrovir arm was also associated with an approximate 80 percent reduction in the risk of death (3/236 in the 3TC+Retrovir group compared to 15/235 in the ddI monotherapy group).

Preliminary HIV surrogate marker results for 3TC+Retrovir through weeks 36-48 reveal median CD4 lymphocyte increases of approximately 73 cells/mm3 versus 4 cells/mm3 for the ddI monotherapy group.

Based on these data, the DSMB recommended to the Pediatric ACTG that the study be stopped immediately, treatment arms be unblinded and the 87 clinical trial sites be notified of the results.

Both treatments had a positive impact on the growth of children under three years of age. Nevertheless, additional studies are still needed to understand late effects and long-term impact of prolonged antiretroviral treatment among children with HIV disease.

The 3TC+Retrovir treatment arm and the ddI monotherapy arm had acceptable safety profiles with only one patient in each group withdrawing due to an adverse reaction. Development of liver abnormalities during the study were more common in the ddI group (15 occurrences versus 5 in the 3TC+Retrovir group), as were instances of pancreatitis (5 in the ddI group versus none in the 3TC+Retrovir group). The most commonly reported grade 3/4 toxicities reported in the 3TC+Retrovir group were low white blood cell counts (7.2 percent), fever (4.7 percent) and anemia (3.4 percent).

Data are not yet available from ACTG 300 on non-serious adverse events. However, in controlled clinical trials in adults, 3TC+Retrovir was generally well tolerated with the most commonly reported side effects being headache, nausea, malaise and fatigue, nasal congestion and runny nose, diarrhea, low white blood cell counts and anemia.

Both 3TC and Retrovir belong to a class of antiretroviral drugs known as nucleoside analogue reverse transcriptase inhibitors. Since the first approval by the U.S. regulatory authorities of 3TC in November, 1995, 3TC has become a widely used foundation for multiple drug combination regimens, including those involving protease inhibitors.

3TC was discovered by BioChem Pharma Inc. Under the terms of a license agreement between BioChem Pharma and Glaxo Wellcome, BioChem receives royalties based on sales of 3TC. Under the terms of the agreement, Glaxo Wellcome has the right to develop, manufacture and sell 3TC worldwide, subject to special arrangements for Canada, where BioChem and Glaxo Wellcome have formed a partnership which is commercializing 3TC.

BioChem Pharma is an international biopharmaceutical company dedicated to the research, development and commercialization of innovative products for the prevention, detection and treatment of human diseases. The Company lists its common shares on the Montreal and Toronto exchanges (BCH) and the NASDAQ National Market (BCHXF).

BioChem Pharma news releases and other company information can be found on the World Wide Web at http://www.biochem-pharma.com.

This press release contains forward-looking statements which reflect the company's current expectation regarding future events. The forward-looking statements involve risks and uncertainties. Actual events could differ materially from those projected herein and depend on a number of factors including the success of the company's research strategy, the applicability of the discoveries made therein, the successful and timely completion of clinical studies and the uncertainties related to the regulatory process.

CONTACT: BioChem Pharma Inc.

Michele Roy, 514/ 978-7938

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