By Jennifer Van Brunt

Editor

Of the 49 new medicines approved for sale in the U.S. by the Food and Drug Administration (FDA) in 1997, 10 were biologics — BeneFIX, Carticel, Infergen, Neumega, Regranex Gel, Rituxan, Zenapax, RabAvert, Infanrix and a DT (diphtheria/tetanus toxoid) vaccine — and many of them were developed by recombinant DNA technology. That's an impressive statistic for the biotechnology industry, which has worked hard over the last 20 years to get to this point. Since 1982, when the first recombinant drug — Eli Lilly and Co.'s Humulin (recombinant human insulin) for treating diabetes (the result of a partnership between the Indianapolis-based pharmaceutical giant and Genentech Inc., of South San Francisco) — was given the FDA's stamp of approval, the agency has approved an average of one or two new biotech-derived biological entities annually.

It wasn't until 1996 that the pace began to pick up, with three unique biologicals receiving marketing clearance. These included Jerusalem-based Teva Pharmaceutical Industries Ltd.'s (NASDAQ:TEVIY) multiple sclerosis drug Copaxone, which is a four-amino-acid peptide derived from myelin basic protein; Cambridge, Mass.-based Biogen Inc.'s (NASDAQ:BGEN) multiple sclerosis drug Avonex (a recombinant human interferon beta-1a); and RespiGam, Gaithersburg, Md.-based MedImmune Inc.'s (NASDAQ:MEDI) polyclonal antibody product to treat or prevent respiratory syncytial virus infection in young children. In its first full year on the market, Avonex reaped $240 million in worldwide sales; RespiGam brought in $45 million. Sales figures for Copaxone were not available.

Not only did the FDA approve more biotech-derived drugs in 1997 than in any previous year, but the agency held true to its goal of speeding up the approval process. According to the FDA's Center for Biologics Evaluation and Research, that arm of the regulatory agency completed 35 major approvals in 1997, covering not only new products and technologies, but also manufacturing methods. The greatest acceleration in its approval process affected 22 products — 11 new product and biological license applications (PLAs and BLAs) and 11 more PLA and BLA supplements. The median time for first-time approvals in 1997 was 12 months, 20 percent shorter than the median time of almost 15.1 months in 1996. And some of those products were speeded through the agency in even shorter times. For instance, BeneFIX, a recombinant DNA-derived clotting factor (human coagulation factor IX) for treating hemophilia B, was approved in about 5.4 months. BeneFIX, developed by Genetics Institute Inc., the Cambridge, Mass.-based subsidiary of American Home Products Corp., which is located in Madison, N.J., received approval for the product in February 1997.

Zenapax, Protein Design Labs Inc.'s (NASDAQ:PDLI) humanized monoclonal antibody that helps prevent kidney transplant rejection by binding to the interleukin-2 receptor of activated T cells, was approved in a mere six months. The product, which was approved in December 1997, will be marketed by Mountain View, Calif.-based Protein Design Labs' partner Hoffmann-La Roche Inc., of Nutley, N.J.

And Rituxan, the first stand-alone monoclonal antibody for treating non-Hodgkin's B cell lymphoma, made it through the regulatory process in 8.9 months. Rituxan, a chimeric pan-B monoclonal antibody that targets the CD20 antigen on the surface of B cells, was developed by Idec Pharmaceuticals Corp. (NASDAQ:IDPH), of San Diego, and its partner Genentech (NYSE:GNE). It was approved in November as a monotherapy for treating relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma — making it the first approved monoclonal-based cancer therapy on the market in the U.S. Roche Holding AG will market the product in Europe; in fact, it was approved for sale in Switzerland — under the trade name MabThera — in late November and is already in the market there. The U.S. launch was effected in mid-December 1997; Genentech reported sales of $5.5 million for 1997 — probably as a result of what the company called a "pent-up demand" for the product.

Other first-time approvals included Regranex, for treating diabetic foot ulcers; Carticel, a product that uses a patient's own cartilage cells to treat certain knee injuries; Neumega, which helps reduce the need for frequent platelet transfusions following chemotherapy; RabAvert, Chiron Corp.'s rabies vaccine; and London-based SmithKline Beecham plc's Infarix, an acellular pertussis, diphtheria and whooping cough vaccine for infants and children.

Regranex Gel (PDGF) received the FDA's coveted mark of approval in mid-December 1997. This product, which was developed by the R.W. Johnson Pharmaceutical Research Institute, part of the Raritan, N.J.-based Johnson & Johnson family of companies, is manufactured and supplied by Emeryville, Calif.-based Chiron (NASDAQ:CHIR). It will be marketed in the U.S. by another Johnson & Johnson company, Ortho-McNeil Pharmaceutical Inc. According to Chiron's most recent financial report (for the quarter ended Dec. 31, 1997), fourth-quarter sales of Regranex reached $11 million, even though the product had barely been approved. This probably represents "pipeline filling," and cannot be taken as an indication of what future sales levels are likely to be.

Genetics Institutes' platelet growth factor recombinant interleukin-11, trade named Neumega, got approved for sale in November — only 11.1 months after first submission — for preventing recurrent, severe, chemotherapy-induced thrombocytopenia in cancer patients. And the FDA approved Genzyme Tissue Repair's (NASDAQ:GENZL) Carticel, which consists of autologous cultured chondrocytes, in 16.9 months . The Cambridge, Mass.-based company's product was approved in August 1997.

Of course, not all products developed by biotech companies are true biologics. Those others fall under the aegis of the FDA's Center for Drug Evaluation and Research (CDER). At least one of them received a priority review in 1997, being whisked through the approval process: Viracept, a protease inhibitor for treating HIV infection, was approved in a mere 2.6 months. It was approved for marketing in March 1997; the drug's developer, San Diego-based Agouron Pharmaceuticals Inc., reported sales of $91.8 million for the quarter ended Dec. 31, 1997.

Another drug approved by CDER was PathoGenesis Inc.'s (NASDAQ:PGNS) product TOBI, the first inhaled antibiotic for patients with cystic fibrosis. The FDA approved the Seattle company's TOBI (tobramycin for inhalation) just days before Christmas. The company reported in its 1997 earnings statement that it had already filled about $5.5 million in pipeline orders of the product.

For these newly approved products, as for those that have preceded them, it will take years before their true market potential becomes apparent.

No Comments