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Innovation Gap Begins to Close As New Product Approvals Rise

By Peter Winter

The biopharmaceutical industry is certainly on a productive roll as measured by its output of new medicines. The number of new drug approvals appears to be steadily increasing year-over-year. The rate at which the FDA has approved new molecular entities (NMEs) – including those filed under new drug applications (NDAs) and therapeutic biologics filed under original biologic license applications (BLAs) is already ahead of last year's total of 30 (24 NMEs, and six biologics).

According to BioWorld Snapshots, which closely tracks new drug approvals, to date 29 NMEs have received the FDA's "green light" together with eight biologics. And this total does not include five other biologics that have also been approved, similar to the number approved last year.

On the PDUFA Runway

There are also three other candidate medicines on the PDUFA runway, scheduled to take place before year end.

Human Genome Sciences Inc. (HGS), now part of GlaxoSmithKline plc, has a PDUFA date of Dec. 15 for its BLA for Abthrax (raxibacumab), a treatment of inhalation anthrax. The drug, a monoclonal antibody targeting the protective antigen component of Bacillus anthracis, has a good chance of being approved following the FDA's Anti-Infective Drugs Advisory Committee voting 16 to 1, with one abstention, in favor of approval.

While antibiotics can kill the anthrax bacteria, they are not effective against the deadly toxins that the bacteria produce. Raxibacumab targets anthrax toxins after they are released by bacteria into blood and tissues. The FDA did issue a complete response letter for raxibacumab in 2009, in spite of the fact that HGS at the time had a $151 million, three-year deal to provide 65,000 doses of the drug to the Strategic National Stockpile. That contract continues to pay out, as HGS collected $6.1 million in sales of raxibacumab to the government in the first quarter of 2012. (See BioWorld Today, May 16, 2012, and Nov. 17, 2009.)

Alexza Pharmaceuticals Inc., of Mountain View, Calif., has a PDUFA date of Dec. 21 for its resubmitted Adasuve new drug application in response to a May complete response letter citing manufacturing deficiencies. Alexza is seeking approval of Adasuve (Staccato loxapine) inhalation powder for acute treatment of agitation associated with schizophrenia or bipolar disorder I in adults. (See BioWorld Today, May 7, 2012.)

The year should close out nicely as far as approvals go. Dec. 30 is the scheduled PDUFA date for NPS Pharmaceuticals Inc.'s Gattex (teduglutide) for short bowel syndrome (SBS). With the FDA's Gastrointestinal Drugs Advisory Committee (GIDAC) voting unanimously for approval it is expected that the FDA will follow this direction.

Assuming that they do the 2012 approval scorecard would total 40 (31 NMEs, and nine biologics), a 33 percent increase over last year and making it a record-setting total.

This torrid pace shows no signs of slowing down with PDUFA dates in January for no less than six candidate medicines.

The product successes that have been achieved in 2012 appear to be "shifting investor focus away from management of pharma's patent cliff woes to a return to growth beyond the cliff," notes a recent Leerink Swann report.

Innovation Gap

Much has been written about pharma's innovation gap where R&D productivity has been declining over the past decade despite the fact that billions have been poured into research and development. The Pharmaceutical Research and Manufacturers of America (PhRMA), for example, found that its member companies invested almost $50 billion in R&D in 2011.

Maybe these investment dollars are finally paying dividends and the innovation gap is beginning to close.

John J. Castellani, PhRMA president and CEO certainly seems to think so and points to the fact that "companies are adapting to a changing research paradigm," reflecting a "shift to a more agile sector, which increasingly involves collaborative, constructive partnerships with both public and private experts."

Other steps that companies are taking include identifying efficiencies and reorganizing research structures throughout the R&D process and improving productivity and achieving other efficiencies through incorporation of new technologies, PhRMA says.

Clinical Trials Collaboration

Clinical trials now represent an aggregate expense of approximately $31.3 billion, or nearly 40 percent of the R&D budget of major drug developers – much of that due to systemic inefficiency, according to a White House report from the President's Council of Advisors on Science and Technology (PCAST). (See BioWorld Today, Sept. 27, 2012.)

Some encouraging signs to improve this situation in fact came a day before the publication of the report with the launch of the nonprofit TransCelerate BioPharma Inc. by 10 of the industry's largest pharmas including Abbott, AstraZeneca plc, Boehringer Ingelheim GmbH, Bristol-Myers Squibb Co., Eli Lilly and Co., GlaxoSmithKline plc, Johnson & Johnson, Pfizer Inc., Roche AG unit Genentech Inc. and Sanofi SA. (See BioWorld Today, Sept. 26, 2012.)

The initiative is seeking to improve the speed and quality of clinical trials by identifying and solving common bottlenecks in trial design and execution.

The FDA can also play a key role in improving drug productivity. This is why the PCAST report is recommending a doubling in the output of new drugs over the next decade, while increasing drug efficacy and safety.

The FDA should expand its existing authorities for accelerated approval and confirmatory evidence to all drugs that meet the statutory standard of addressing an unmet need for a serious or life-threatening disease, together with full enforcement of the agency's requirement for post-approval confirmatory studies, PCAST recommended. The FDA could use the accelerated approval pathway for a wider range of serious or life-threatening diseases than it does currently on the basis of a surrogate endpoint.

In addition, the report called for stronger postmarketing surveillance and communication tools to generate evidence on the benefits and risks of drugs and to communicate those outcomes to the public, and "greater clarity" from the FDA about general regulatory pathways for innovative products and approaches.

It looks as though the FDA is responding positively. In its just-released Innovative Drug Approvals for FY 2012 report, which covers the Oct. 1, 2011, to Sept. 30, 2012, period, the agency said that it matched its performance in FY 2011 and approved 35 new medicines during the year. (See BioWorld Today, Dec 7. 2012.)

The FDA said it continues to strengthen its ability to monitor drug safety, and one of the contributing factors for that is the Sentinel Initiative. (See BioWorld Today, July 6, 2011.)

The program is designed to harness a broad network of health care databases to detect and understand drug risks. A pilot program for the initiative called Mini-Sentinel is now able to access electronic health information derived from 159 million patients and perform rapid assessments when there is an early signal that a marketed drug may have a safety problem.

Also, the agency points to its improved ability to process more than a million adverse event reports it receives annually thanks the implementation of their FDA Adverse Event Reporting System (FAERS).

Given the success to date of the Sentinel project the agency will welcome the PCAST recommendation to Congress to authorize line-item appropriations of $40 million per year to expand the system.