Last year was lean for biotech drug approvals in the U.S. TheFDA granted marketing rights to only two: Chiron/Cetus'Interleukin-2 and Genetics Institute Inc. (GI)/BaxterHealthcare's Factor VIII.

FDA also approved a biotech diagnostic, Cytogen Corp.'sOncoScint, the first monoclonal antibody-based in vivo imagingagent to receive U.S. marketing approval.

And 1993 might be only slightly better. "I'm not expecting amassive number of major new drug approvals in 1993," DeniseGilbert, an analyst with Smith Barney, told BioWorld. Gilberthas only two candidates on her list: Genentech Inc.'s Kogenate(Factor VIII) and Xoma Corp.'s CD5 Plus. But she included onediagnostic imaging agent, Centocor Inc.'s Myoscint.

Merrill Lynch & Co.'s Stuart Weisbrod also picked Myoscint,even though "this is a small product and won't make a majordifference for Centocor." Weisbrod also foresees broad approvalfor Immunex Corp.'s Leukine, and predicted that FDA will givethe nod to Chiron Corp.'s Betaseron. David Stone of Cowen & also betting on Betaseron, Genentech's Factor VIII and DNase,and GI/Sandoz/Schering-Plough's Leucomax (GM-CSF), as wellas several diagnostics and Genzyme Corp.'s recombinantversion of Ceredase.

Compared with the number of biotech drugs in development,that's not a long list. But it's not unexpectedly short, either. Bycomparison, in 1991 FDA approved only Immunex Corp.'sLeukine (granulocyte macrophage colony stimulating factor, orGM-CSF) and Amgen Inc.'s Neupogen (granulocyte colonystimulating factor, or G-CSF).

The Pharmaceutical Manufacturers Association (PMA), whichconducts an annual review of new drug approvals, observedthat "during the past nine years, 14 biotech drugs have beenapproved -- an average of only about one-and-a-half approvalsper year."

The rate of approval, however, may improve in the long term,according to G. Steven Burrill, national director ofmanufacturing and high technology industry services for Ernst& Young of San Francisco. Burrill said FDA will get moreresources that will eventually result in an accelerated productapproval process, especially with $100,000 in user fees comingto FDA with new drug applications.

Still, Burrill said FDA will continue to focus on drugs thataddress the "life-threatening end of the spectrum," paying "lessattention to products for less life-threatening situations." Whileit took FDA only five months to approve Taxol for treatingadvanced ovarian cancer and about six months to approve AZTfor treating AIDS, it took the agency about 13 months toapprove Leukine and Neupogen in 1991 -- still a vastimprovement over the 1991 average new drug approval timeof 30 months.


Kogenate Factor VIII:C

Kogenate Factor VIII:C is the recombinant human blood clottingfactor VIII made by South San Francisco, Calif.-basedGenentech Inc.'s (NYSE:GNE) licensee, Miles Laboratories. Mostobservers predicted imminent approval, especially since onefactor VIII, GI/Baxter Healthcare's Recombinate, got the go-ahead on Dec. 10. The two drugs were recommended forapproval simultaneously in December 1991 by FDA's BloodProducts Advisory Committee.

While the GI/Baxter product is approved for use only inpreviously treated hemophilia patients, the FDA committeerecommended that the Genentech/Miles product could be usedin patients who had not been treated for hemophilia A, as well.The PLA on Kogenate was filed in the third quarter of 1989.

Armand Famiglietti, Miles' director of marketing forhemostasis, told BioWorld that "there are no outstandingproduct issues" with FDA. "We believe approval is imminent."

Pulmozyme (DNase)

Genentech completed Phase III clinical trials in December onthis recombinant DNase for treating cystic fibrosis. The 968-patient study demonstrated that Pulmozyme improves lungfunction and reduces the rate of respiratory infection, with nomajor adverse side effects. Genentech expects to file its PLA byMarch, and will submit a thorough data analysis of the trials inlate January at the Intermountain Thoracic Society Meeting.


Betaseron is a beta-interferon analog being developed fortreating multiple sclerosis, an indication for which FDA grantedit orphan drug status.

Chiron (NASDAQ:CHIR) of Emeryville, Calif., and its marketingpartner Berlex Laboratories Inc. of Cedar Knolls, N.J., (the U.S.subsidiary of Schering AG) filed a PLA last June on Betaseronfor treating relapsing remitting multiple sclerosis (MS) patients(those who suffer from episodic losses of motor skills). Thecompanies have not released any trial data, though."Betaseron's exact chemical benefits and efficacy haven't beenpublished," said Larry Kurtz, Chiron's vice president ofcorporate communications.

Betaseron was initially developed by a joint venture betweenCetus Corp. (with which Chiron later merged) and ShellChemical. When Shell founded Triton Biosciences, it became aCetus-Triton joint venture. Triton was sold to Schering in 1991,and the drug became part of Berlex. Although Triton wasconducting advanced clinicals on Betaseron for treating AIDSand ARC patients, Berlex "is not pursuing clinical trials in thatarea at this time," said Wendy Neininger, Berlex's director ofcorporate communications. But the company is planning toinitiate clinical trials of Betaseron in patients with chronicprogressive multiple sclerosis in 1993, she told BioWorld.

CD5 Plus

CD5 Plus is Xoma Corp.'s (NASDAQ:XOMA) monoclonal antibodylinked to a toxin, the A chain of ricin. The Berkeley, Calif.,company was developing the product for treating variousautoimmune diseases -- including rheumatoid arthritis,psoriasis, lupus erythmatosus and acute graft vs. host disease(GvHD) -- but is now seeking approval only for the GvHDindication, for which it filed a PLA in the fourth quarter of1988. The FDA's Biological Response Modifiers reviewcommittee recommended approval for this indication in June1991, with the caveat that approval was "contingent on a goodfaith effort by the manufacturer to obtain a satisfactory recentcontrol group." Xoma had used historical rather than clinicalcontrol data on its PLA. Carol DeGuzman, Xoma's director ofcorporate communications, told BioWorld that "there are nooutstanding issues" remaining with FDA.


Myoscint, Centocor Inc.'s (NASDAQ:CNTO) monoclonal antibody-based cardiac imaging agent, radiolabeled with indium-111,uses a fragment of a monoclonal to bind dead heart tissue. AnFDA advisory committee recommended its approval fordetecting the presence, location and extent of myocardialnecrosis in acute ischemic heart disease in November 1991. TheMalvern, Pa., company filed its PLA in the second quarter of1988.

Leucomax and Leukine

Leucomax is the granulocyte macrophage-colony stimulatingfactor (GM-CSF) being developed by Genetics Institute Inc.(NASDAQ:GENIZ) of Cambridge, Mass., its licensee Sandoz Ltd.and its sublicensee Schering-Plough Corp. for marrowtransplants, neutropenia and AIDS. Sandoz and Schering filedfor U.S. marketing approval in January 1990 for using the drugto treat the neutropenia caused by chemotherapy.

Immunex Corp. (NASDAQ:IMNX) of Seattle has also developedGM-CSF -- as Leukine -- for which it received FDA marketingapproval in March 1991 to accelerate marrow engraftmentfollowing autologous bone marrow transplantation to treatcertain cancers. Leukine received additional approval lastJanuary for treating cancer patients whose bone marrowtransplants have failed. Immunex filed for a broader labelindication for Leukine in the third quarter of 1992.

-- Jennifer Van Brunt Senior Editor

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