Guidance and Strategies for Spurring Development of New Therapies

Everyone is looking to rev up the biopharmaceutical development pipeline, and the FDA is working hard to do its part. The agency is publishing guidances and updating rules to clarify its approaches for testing new drugs, many required by the FDA Safety & Innovation Act of 2012 (FDASIA) and its user fee programs.

To move drug candidates through the review process more efficiently, FDA issued a much-anticipated guidance in June that compares the objectives and requirements of four FDA programs to expedite the development and review of new drugs and biologics: fast track, accelerated approval, priority review, and the relatively new breakthrough therapy designation (http://1.usa.gov/12IZNWi). A chart lists qualifying criteria, sponsor actions, and the features and benefits of each designation. In the process, the guidance defines when a condition can be considered "serious," how to determine whether "existing" treatment is "available," and what kinds of conditions qualify as an "unmet medical need."

There's also new guidance for biopharma companies looking to co-develop two or more investigational drugs, designed to spur research on combination therapies to treat complex critical diseases such as cancer, serious infections, and cardiovascular disease. The guidance advises sponsors on determining when codevelopment might be appropriate and how to conduct nonclinical and clinical studies to test the safety and efficacy of individual compounds and the drugs in combination.

To assist the growing number of pharma companies looking to develop therapies for rare diseases, FDA updated its 1992 orphan drug regulations with a new rule published in the Federal Register, June 12, 2013. The revision aims to define more clearly what constitutes an "orphan subset" and clarify policies for obtaining designation as an orphan drug. Another new proposed rule meets a FDASIA requirement to speed the development of new pediatric treatments by requiring sponsors to submit pediatric study plans earlier in the testing process.

Additional documents advise sponsors on providing patients with access to promising critical therapies still being tested. One draft guidance issued in May clarifies FDA's process for permitting expanded access to investigational new drugs for patients seeking treatment, and another discusses policies for companies seeking to charge for investigational drugs made available under expanded access.

To avoid premature disclosure of investigations into research misconduct by individuals, FDA has issued a final rule that permits it to keep certain investigatory material confidential. Normally, the Privacy Act gives individuals the right to information compiled on them by a federal agency, but FDA is exempt in cases where research fraud might be involved and disclosure would jeopardize the integrity of FDA research misconduct proceedings.

Tackling conditions

Then there's a range of advisories on developing drugs to treat specific conditions or diseases. Last month, the Center for Biologics Evaluation and Research (CBER) issued a draft guidance on designing early-phase clinical trials for cellular and gene therapy products. CBER acknowledges that the distinctive features of these products may warrant different approaches to choosing a study population, using a control group, dose selection, monitoring, and study follow-up.

Another draft guidance aims to encourage development of new antibacterial therapies, supporting a FDASIA program for generating new antibiotics. It encourages innovative research approaches, such as pooling data from various sites, adopting new endpoints, and using animal data to complement clinical results.

Recent guidances also discuss developing drug products for rheumatoid arthritis and for antiretroviral drugs for treating HIV. Sponsors can gain additional insight into new research strategies through FDA public meetings designed to gain input on patient-focused strategies for developing HIV treatments and therapies for lung cancer.

Rescuing abandoned drugs

Another much-discussed strategy for spurring new drug development is for academic scientists to take a fresh look at compounds that pharma companies started to develop, but dropped along the way. Now the National Institutes of Health (NIH) drug "repurposing" initiative has moved forward, with a first round of grants totaling $12.7 million from the National Center for Advancing Translational Sciences (NCATS). The awards will support nine projects to conduct further research on compounds that pharma companies have stopped testing, largely due to poor efficacy or for business reasons.

Astra Zeneca, Eli Lilly, Johnson & Johnson's Janssen, Pfizer, and Sanofi are supplying the compounds for these first projects, which will be tested collaboratively in pre-clinical through Phase II studies (http://1.usa.gov/12GVji5). Industry has been skeptical that the NCATS repurposing program will bear fruit, but the initiative has strong backing from NIH Director Francis Collins as a strategy for accelerating discovery of new therapies for critical diseases.