FDA’s 26 NEW MOLECULAR ENTITY APPROVALS IN 1992 ARE FEWER THAN RECORD 30 NME CLEARANCES IN 1991 BUT ARE IMPROVEMENT OVER AGENCY PERFORMANCE FROM 1986-1990

FDA's approval of 26 new molecular entities in 1992 is slightly below the agency's record level of 30 NME approvals first set in 1985 and repeated in 1991 ("The Pink Sheet" Jan. 4, p. 19). However, FDA's approval performance in the past year is an improvement over the number of agency actions taken during 1986 through 1990, when the number of NME approvals ranged from 20 to 23. Interestingly, 1985 and 1991 each represent the first full years in office of FDA commissioners -- Young in 1985 and Kessler in 1991. FDA also approved a total of 91 NDAs in 1992, which is 28 more than it okayed in the previous year. FDA reviewed the 1992 NMEs in an average of 30 months -- basically the same average approval time for the 1991 NMEs, which was 30.3 months ("The Pink Sheet" Jan. 6, 1992, p. 13). In 1990, the average NME approval time was 27.7 months. All 91 NDAs were approved in an average of 32.6 months versus 28.5 months for the 1991 NDAs. The 10-year approval time for Searle's nonsteroidal anti- inflammatory drug Daypro (oxaprozin) prevented FDA from improving on the previous year's 30-month average approval time for NMEs. Daypro's approval time is the longest in memory, FDA said. NSAID applications often inflate FDA review times: in 1991, Wyeth- Ayerst's Lodine NSAID was approved after an eight-year review and SmithKline Beecham's Relafen after five years and nine months of agency scrutiny. The 1992 average approval time also was affected by long review periods for Fison's inhaled anti-inflammatory Tilade (nedocromil), Pfizer's calcium channel blocker Norvasc (amlodipine) and Bristol-Myers Squibb's anti-arrhythmic Betapace (sotalol). Those drugs were approved in five years and 10 months, four years and seven months, and four years and four months, respectively. FDA continued its tradition of approving a large number of drugs at the end of the year. The percentage of December approvals went up slightly in 1992. As in 1991, the agency again approved nine NMEs during December, but in 1992, those nine accounted for 34% of the total as opposed to 1991 when December approvals accounted for 30% of the NME's cleared. Fewer NMEs (two) were approved at the beginning of 1992 than in the first month of 1991 (five). Although, the initiation of a new ratings system for NMEs did not appear to have much of an impact on overall review times, the "1P" (priority review) drugs had a faster median approval time than the "A" and "B" drugs had in 1991, 14.2 months versus 17 months. However, the average approval time for all priority drugs (not limited to NMEs) was 18.1 months in 1992 versus 16.8 months in 1991. Last year marked the start of "1P" and "1S" (standard review) designations that Vice President Quayle's Council on Competitiveness had recommended to FDA to replace the former "A", "B" and "C" designations. The new ratings were suggested as a way to facilitate accelerated approval of drugs for life-threatening or very serious diseases and to simplify the tracking of applications. During 1992, the agency approved four NMEs that can be used for treating AIDS or AIDS-related conditions, a record number of approvals for the fatal disease. Roche's Hivid (zalcitabine or ddC) is the third drug to be approved specifically for treating AIDS after Bristol-Myers Squibb's Videx (didanosine or ddI) and Burroughs Wellcome's Retrovir (zidovudine or AZT). As an AIDS drug, Hivid received expedited review and was approved in eight months. Adria's macrolide antibiotic Mycobutin (rifabutin) was approved as the first drug for prophylaxis of Mycobacterium avium complex in AIDS patients ("The Pink Sheet" Jan. 4, 1993, p. 13). Burroughs' Mepron (atovaquone) was okayed by FDA in November for treatment of Pneumocystis carinii pneumonia in patients who are intolerant to trimethoprim/sulfamethoxazole. Janssen's antifungal Sporanox (itraconazole) was cleared in September, after expedited review, for treating fungal infections in immunocompromised and non-immunocompromised patients. And, following approval of a supplemental NDA on Dec. 22, Unimed's Marinol (dronabinol) will be the first product marketed for treating anorexia in AIDS patients ("The Pink Sheet" Jan. 4, 1993, p. 14). One 1992 drug approval that stands out is Bristol-Myers Squibb's Taxol (paclitaxel), approved for treatment of refractory ovarian cancer ("The Pink Sheet" Jan. 4, p. 8). The development and review of Taxol represented a concerted effort by FDA, the National Cancer Institute, Bristol-Myers Squibb and Canada's Health Protection Branch that was reflected in the drug's quick review time of five months. Taxol's review period is the shortest in memory for a cancer drug, FDA said. Adding to the high visibility of Taxol's approval were the negotiations between Bristol and NCI to hold down the price of the anticancer agent. Taxol is difficult to manufacture since it is derived from the bark of the rare Pacific yew. Another significant approval was for a new migraine treatment, Glaxo's Imitrex (sumatriptan injection). Imitrex is expected to revolutionize the treatment of migraine given the inadequate drug armamentarium that is currently available for the condition and size of the underserved patient population. An NDA for an oral form of the drug is pending at FDA. The first drug product for treating symptomatic benign prostatic hyperplasia was approved in 1992. Merck's Proscar (finasteride) was okayed by FDA in June as a treatment for a chronic condition that affects 60% of men over age 50. The only other available treatment for BPH is surgery, which is usually indicated for patients with worsening symptoms. Boots' Manoplax (flosequinan), approved during the end-of-the- year rush, is the first of a new class of fluoroquinolone heart drugs that acts as a direct vasodilator. Manoplax is indicated for congestive heart failure patients who are unresponsive to standard CHF therapies and for patients intolerant to angiotensin- converting enzyme (ACE) inhibitors. According to estimates provided by Boots, there are 3 mil. CHF patients diagnosed in the U.S. annually and 25% of them are intolerant to or inappropriate candidates for ACE inhibitors. Once available in March, Manoplax will be comarketed by a combined Boots and Parke-Davis sale force of 600 sales reps. Boots and Parke-Davis are also copromoting Lopid (gemfibrozil). On top of traditional medical journal advertising, Manoplax will be discussed in patient brochures about CHF provided to physicians' offices. In addition to Marinol, FDA approved several other significant supplemental indications and/or dosage forms during 1992. The agency provided another long-acting contraceptive option when it approved Upjohn's Depo-Provera in October. The approval of Depo- Provera came after 20 years of controversy over whether the injectable contraceptive is safe and effective. Glaxo's oral Zofran (ondansetron) was approved at the end of the year for the prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy. Zofran injection was approved in 1991 for prevention of nausea and vomiting associated with emetogenic cancer chemotherapy, including high-dose cisplatin. FDA's Division of Anti-Infective Drugs approved the most NMEs (six) in 1992: Abbott's Omniflox (temafloxacin), Searle's Maxaquin (lomefloxacin), SmithKline's Halfan (halofantrine), Upjohn's Vantin (cefpodoxime), Block Drug's Actinex (masoprocol) and Sandoz' Lamisil (terbinafine). However, in June, Omniflox was withdrawn from the market worldwide after the firm received 50 reports of serious adverse reactions, including three deaths, following the drug's U.S. launch in mid-February. Behind the anti-infective drug division in number of NME approvals were the Division of Anti-Viral Drugs and the Division of Cardio-Renal Drugs, both with four approvals. The Pilot Drug Evaluation Staff and the Division of Oncology & Pulmonary Drugs showed their productivity by approving three NMEs each. The pilot staff also approved 13 other NDAs. At the beginning of 1992, the pilot drug staff led drug reviewing divisions in the Center for Drug Evaluation and Research with 21 overdue NDAs. However, according to recent FDA figures, the group currently has no backlog of overdue NDAs. The Pilot Drug Evaluation Staff also has significantly reduced the number of overdue efficacy supplements to 10. The pilot drug group attributes its success in slashing the application backlog to the innovative review approaches it has developed, including use of sessions to plan out the review of each application, NDA Days, and delegating approval sign-off authority to several staff members. The Division of Anti-Infective Drugs and the Division of Oncology & Pulomonary Drugs also have no overdue NDAs awaiting review. FDA made significant inroads in decreasing the overall number of pending overdue NDAs during 1992. At the end of the year, the agency had 18 overdue NDAs during 1992, which is significantly less than the 50 that were pending in 1991. Several NMEs are expected to be signed off on in January. Possible candidates for approval include Janssen's gastric motility agent Propulsid (cisapride), two nonsedating antihistamines: Schering's Claritin (loratadine) and Pfizer's Reactine (cetirizine), Ortho's hairy cell leukemia drug Leustatin (2-CdA) and Sterling's imaging agent Omniscan (gadodiamide).