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FDA’s New Initiatives Taking Off
In early 2003, the FDA set in motion a series of new initiatives aimed at reducing the time for drug and biologic product approvals. In particular, the agency said that it is “committed to reducing total review time for new drugs and biologics across the board by approximately 10.5 percent.” To accomplish this, the FDA is working hard to decrease the number of applications requiring multiple review cycles. It’s also set up numerous collaborations with the NCI, other government agencies, academic researchers, health care providers and patients to “clarify regulatory pathways for targeted disease areas and new technologies.”
Ambitious goals, to be sure. But commissioner Mark McClellan has managed to light a fire under the agency, and the results are already apparent. We even saw evidence of it in the waning days of 2002, when the FDA approved Humira -- a monoclonal antibody for treating rheumatoid arthritis developed by Cambridge Antibody Technology Group plc and Abbott Laboratories – in eight months, about two months earlier than expected, and without the need for an advisory committee meeting.
And in early 2003, Biogen Idec Inc.’s new psoriasis product Amevive garnered the FDA’s blessing nearly two months early: The agency had committed to completing its review by mid-March, but granted approval on January 31.
Several drugs benefited from accelerated approvals in 2003. For instance, Trimeris Inc.’s AIDS drug Fuzeon, the first drug to block HIV’s entry into immune cells, was approved in six months. Millennium Pharmaceuticals Inc.’s myeloma drug Velcade flew through the approval process in four months – two months ahead of schedule and based on Phase II clinical trial data. And AstraZeneca plc’s lung cancer therapy Iressa was also approved based on Phase II data, but this approval took nine months, primarily because the agency needed to first examine the data on patients in Japan who had died of serious lung disorders after taking the drug.
These rapid approval times are good news, indeed, and clearly demonstrate that Commissioner McClellan is dedicated to implementing his bold plan to revitalize the FDA. But because many NDAs and BLAs were filed long before these new initiatives came into play, it will take a number of years before we see across-the-board reductions in product-approval times. Many of these older applications have been under review for years, and their regulatory paths are strewn with setbacks – including the need for sponsoring companies to conduct additional clinical trials.
In fact, several of the biotech products approved in 2003 fall into this category – including Corixa Corp.’s non-Hodgkin’s lymphoma therapy Bexxar (47 months from the time the BLA was first filed to marketing approval) and Praecis Pharmaceuticals Inc.’s prostate cancer drug Plenaxis (35 months).
But what were the median and average product-approval times for last year? And how do they compare to prevous years? To determine this, we calculated those data for the biotech drugs and biologics approved in 2000 through 2003 – and compared those to products approved in 1996 -- a high point in the FDA's history. (For a list of biotech products approved in 1996, please refer to the Signals article, “Ghost In The Machine.” For a list of products approved in 2000, click here. For 2001 approvals, click here. For 2002 approvals, click here. The biotech drugs and biologics approved in 2003 – as well as the time to approval for each – are listed at the end of this article.)
As shown above, the average approval time for new biotech-derived biologics was just a tad longer in 2003 than it was in 1996 – 24.8 months versus 24.4 months. Conversely, the average approval time for new biotech drugs actually decreased: In 1996, it was 19.4 months; in 2003, it was 17.6 months. The real slowdown occurred in 2002 – and affected both drugs and biologics.
In its annual report on new drug approvals, the Pharmaceutical Research and Manufacturers of America (PhRMA) found the same trends. For all new biologics, the average time to approval in 1996 was 24.5 months; in 2003, it was 34.7 months (an increase of 42 percent). And, for all new drugs, the PhRMA determined that the average approval time in 1996 was 17.8 months; in 2003, it dropped slightly, to 16.9 months (a decrease of 5 percent).
The median approval time for biotech company-derived biologics was also longer in 2003 than it was in 1996 – 24.5 months versus 18 months (an increase of 36 percent). Conversely, median drug approval times dropped, from 16 months in 1996 to 10 months in 2003 (a decrease of 38 percent).
Thus, the data indicate that approval times for new drugs – whether they come from the biotech sector or big pharma – have decreased since 1996. On the other hand, approval times for new biologics – whether they’re developed by biotech firms or pharmaceutical houses – have increased since 1996.
And that is where the FDA has got its work cut out for it – to shave precious months off the approval process for new biologics.
The following biotech-developed drugs (and a few developed by big pharma that are considered relevant to the industry) were approved under NDAs in 2003. The elapsed time from NDA submission to approval is noted in parentheses. For rolling NDAs, the submission date is the date on which the submission was completed. For the products Estrasorb, Namenda and Plenaxis, each of which involved a resubmission of the NDA, the submission date is the date on which the NDA was originally submitted.
§ Aloxi. The 5-HT3 receptor antagonist, developed by MGI Pharma Inc. and Helsinn Healthcare S.A., was approved in July for preventing nausea and vomiting caused by cancer chemotherapy. (10 months)
§ Cialis. Developed by Lilly ICOS LLC, this phosphodiesterase inhibitor was approved in November for improving erectile function up to 36 hours after dosing. (29 months)
§ Cubicin. Cubist Pharmaceuticals Inc. in-licensed this injectable antibiotic from Eli Lilly and Co., which had taken it through Phase II trials. The FDA approved Cubicin in September for treating complicated skin and structure infections caused by Gram-positive microorganisms. (9 months)
§ Emtriva. Originally developed by Triangle Pharmaceuticals Inc., which Gilead Sciences Inc. acquired in January 2003, this nucleoside reverse transcriptase inhibitor was approved as a once-daily medication for treating HIV infection in July. (10 months)
§ Estrasorb. Novavax Inc.’s cream formulation of estradiol was approved in October as a topical estrogen replacement therapy for reducing hot flashes in menopausal women. (28 months)
§ Factive. GeneSoft Pharmaceuticals Inc. (recently acquired by Genome Therapeutics Corp.) in-licensed Factive, a fluoroquinolone antibiotic, from LG Life Sciences, a Korean firm that originally discovered the drug before out-licensing it to SmithKline Beecham. In December 1999, SKB filed an NDA on this drug, but the FDA issued a non-approvable letter in 2000. After SKB and Glaxo Wellcome merged, LG Life Sciences reacquired all rights to Factive. In April 2003, Factive was approved for treating community-acquired pneumonia and bacterial exacerbation of chronic bronchitis. (40 months)
§ Fuzeon. Fuzeon is the first HIV therapy that blocks the virus from entering immune cells. The FDA granted accelerated approval to Trimeris and Roche’s NDA in March 2003. (6 months)
§ Iressa. AstraZeneca’s epidermal growth factor receptor inhibitor was approved in May as a third-line therapy for patients with advanced non-small cell lung cancer. The FDA granted accelerated approval to this drug based on Phase II data. (9 months)
§ Lexiva. This protease inhibitor was developed by Vertex Pharmaceuticals Inc. and GlaxoSmithKline. It received FDA approval in October for treating HIV infection, with once- or twice-daily dosing, with or without food or water restrictions. (10 months)
§ Namenda. Developed by Neurobiological Technologies Inc., Merz + Co. and Forest Laboratories Inc., this NMDA receptor antagonist was approved in October for treating moderate-to-severe Alzheimer’s disease. (15 months)
§ Plenaxis. This synthetic peptide that acts as a gonadotropin-releasing hormone antagonist was developed by Praecis Pharmaceuticals. The FDA approved the drug in November for the palliative treatment of advanced prostate cancer. (35 months)
§ Rebetol Oral Solution and Capsules. Rebetol, a synthetic nucleoside analog, was already approved in table formulation. Schering-Plough Corp.’s new oral solution was approved in July for use in combination with Intron A to treat chronic hepatitis C virus infection in patients 3 years of age or older. (6 months)
§ Risperdal Consta. This long-acting formulation of an anti-psychotic drug was developed by Alkermes Inc. and Johnson & Johnson Pharmaceutical Research & Development LLC. The FDA approved the drug in October for the management of schizophrenia. (27 months)
§ Somavert. Pfizer Inc.'s PEGylated human growth hormone analog Somavert was developed by Sensus Drug Development Corp., which Pfizer (Pharmacia at the time) acquired in March 2001. The FDA approved the product for treating acromegaly in March. (27 months)
§ Striant. Columbia Laboratories Inc.’s formulation of testosterone, which is delivered through a tablet adhered to the gums, was approved in June as a hormone replacement therapy for men. (10 months)
§ Velcade. Millennium Pharmaceuticals’ small molecule proteasome inhibitor was granted accelerated approval, based on Phase II trial data, in May for treating relapsed and refractory multiple myeloma. (4 months)
§ Zavesca. Developed by Oxford GlycoSciences plc (which was subsequently acquired by Celltech Group plc), Zavesca is a small molecule inhibitor of glycosyltransferase. The FDA approved the drug in August for use in Gaucher disease patients for whom enzyme replacement therapy is not an option. (24 months) |
The following biologics (a few of which were developed by big pharma) were approved under BLAs in 2003. The elapsed time from BLA submission to approval is noted in parentheses. For rolling BLAs, the submission date is the date on which the submission was completed. For the product Bexxar, which involved a resubmission of the BLA, the submission date is the date on which the BLA was originally submitted.
§ Advate. Baxter International Inc.’s recombinant Factor VIII product was approved in July for treating hemophilia A. The new formulation contains no human or animal plasma or albumin, thereby eliminating the risk of infection caused by viruses or other agents. (13 months)
§ Aldurazyme. Developed by BioMarin Pharmaceutical Inc. and Genzyme Corp., this recombinant alpha-L-iduronidase was approved in April for use as an enzyme replacement therapy in patients with mucopolysaccharidosis. (9 months)
§ Amevive. Biogen Idec’s human fusion protein that targets a subset of T cells and interferes with lymphocyte activation was approved in January for treating moderate-to-severe chronic plaque psoriasis. (17 months)
§ Bexxar. Originally developed by GlaxoSmithKline and Coulter Pharmaceutical Inc. (which was acquired by Corixa), this I-131-labeled murine monoclonal antibody to the CD antigen on B cells was approved on June for treating non-Hodgkin’s lymphoma. (47 months)
§ Fabrazyme. Genzyme’s recombinant human alpha-galactosidase A was approved in April for use as an enzyme replacement therapy in patients with Fabry disease. (34 months)
§ FluMist. Initially developed by Aviron (since acquired by MedImmune Inc.), this attenuated, cold-adapted live virus, intranasal vaccine was approved in June for preventing influenza in healthy people between the ages of 5 and 49. (32 months)
§ Raptiva. Xoma Ltd. and Genentech Inc. developed this humanized monoclonal antibody to T cells. The FDA approved the product in October for treating chronic moderate-to-severe plaque psoriasis. (10 months)
§ Xolair. Developed by Genentech, Tanox Inc. and Novartis AG, Xolair is a humanized anti-IgE monoclonal antibody that the FDA approved in June for treating allergic asthma. (36 months) |
originally published 02/09/2004 |