Sequus Pharmaceuticals Inc. has received market clearance from theFDA for Amphotec, an antifungal antibiotic used for the treatment ofaspergillosis in patients where renal impairment or unacceptabletoxicity precludes the use of conventional amphotericin B and inpatients where prior antifungal therapy has failed.
Amphotec is a lipid-based formulation using a new 1-for-1 molecularcomplex of amphotericin B and a metabolite of cholesterol,cholesteryl sulfate.
"We are ready to take this product to market immediately, I. CraigHenderson, chairman and CEO of Sequus, told BioWorld Today. "Itis just a matter of completing the labeling and packing the vials. Wehave had final FDA approval, with no ifs, ands or buts."
Amphotec is Sequus' second drug to be cleared for marketing in theU.S. in less than a year. Doxil, a long-circulating Stealth liposomeformulation of doxorubicin, an anti-cancer drug, was launched inDecember of 1995 for treatment of AIDS-related Kaposi's sarcomain patients whose disease has progressed on prior combinationchemotherapy or in patients who are intolerant to such therapy.
Sequus, Henderson, said, is now preparing to launch Amphotec in theU.S. For territories outside the U.S., he said, Sequus has marketingand distribution agreements with several companies, includingZeneca Pharmaceuticals, of London, Prodesfarma, S.A. and TorrexPharma GmbH. The drug is currently being marketed in 17 countiesoutside the U.S. under the name of Amphocil.
Amphotericin B, a broad spectrum antifungal antibiotic, isconsidered to be the "gold standard" for treating progressive andpotentially fatal systemic fungal infections which frequently occur inpatients receiving chemotherapy, AIDS patients or patients who havehad a transplant.
Despite its therapeutic effectiveness, the use of amphotericin B islimited by its acute and chronic toxicities, particularly dose-limitingtoxicity to the kidneys. Amphotec is designed to enhance systemicantifungal therapy by reducing the dose-limiting toxicities associatedwith amphotericin B while maintaining efficacy. The most commonside effects of Amphotec are chills and fever upon infusion,Henderson said.
Amphotec, Henderson said, faces serious market competition fromThe Liposome Co.'s Abelcet, another lipid-based antifungalantibiotic, which has done between $30 million and $40 million insales its first year on the market.
Amphotec, he pointed out, has advantages over Abelcet that willgive it an edge in the marketplace. "There have been reports ofserious interactions between Abelcet and cyclosporin, which is givento transplant patients to retard rejection," he said, adding thatAmphotec works well with cyclosporin.
Also, the use of Amphotericin B is limited by its acute and chronictoxicities, particularly to the kidneys. Abelcet and Amphotec bothgive the same antifungal affect, but Amphotec is less toxic to thekidney than Abelcet, he said.
Amphotec will be coming in at a lower price (which the company didnot reveal), which is an important advantage.
Mary Ann Gray, an analyst with Dillon, Read & Co. Inc. in NewYork, said the future looks bright both for Amphotec and thecompany. "Sequus is a fantastic company that has been under-appreciated in the marketplace. It is beginning to deliver on itspromises and investors have come back. I see Sequus as an extremelyattractive value," Gray said.
Results from additional clinical studies of Amphotec indicated safetyof the drug in bone marrow transplant patients at doses up to 7.5mg/kg a day. In a 343-patient trial with patients with proven orsuspected aspergillosis showed a response rate of 49 percent in theAmphotec groups compared to 23 percent in the historicalamphotericin B control group. The Amphotec-treated group showedbetter survival at 120 days.
The overall response rate for Amphotec was 53 percent and 67percent in patients with candida infections. An analysis showed that80 percent of patients treated with amphotericin B may develop renaltoxicity, compared to 12 percent for Amphotec.
Gray's figures showed that Amphocil sales in the first nine month of1996 were slightly over $1 million. Abelcet, she said, showedworldwide sales of approximately $36 million for the first ninemonths of 1996.
"We expect Amphocil sales outside the U.S. to ramp up slowly,"Gray said. "in the U.S., we expect Amphotec sales to begin prior toyear end and to ramp up faster in Europe with 1997 sales of almost$20 million. Abelcet will continue to be the lead product initiallybecause of its early foothold in the market and its broader labelindications, but we expect the antifungal market share of lipid-basedamphotericin B products to grow significantly."
Sequus, founded in 1981, is located in Menlo, Calif. The companysaid approximately $150 million was spent to develop and initiatecommercialization of Doxil and Amphotec.
Sequus stock (NASDAQ:SEGU) closed Monday at $13.250, down$0.375. n
-- Frances Bishopp
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