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Exclusive Life Science Feature rheumatoid arthritis, inflammatory bowel disease, and psoriasis as our top areas of investment." Hait uses the following questions to determine which drugs to move forward internally. What is the unmet need? How compelling is the science? How innovative is the product? Does the drug work, and how well? How different is it from other drugs in the space, or those being advanced by other companies? In addition, the company calculates the net present value for all of the company's drug assets to assist in prioritizing. This calculation becomes more precise as the drug develops, as a lot of preliminary calculations are based on the probability of technical and regulatory success (see sidebar "Approaches For Calculating Net Present Value [NPV] For Drug Discovery"). "If the drug isn't highly innovative, differentiated, with high activity early on, it gets killed very early," he attests. "Low activity, a me-too type of drug, all sorts of problems in early development, or preclinical toxicity issues should be red flags to kill a drug quickly." There are other reasons to focus on unmet medical needs as well; namely, the FDA has created incentives for those companies that do and gives rewards for those that are successful. FDA INCENTIVIZING BREAKTHROUGHS, NOT BLOCKBUSTERS The FDA's breakthrough therapy designation was enacted to expedite the development and shorten the review time for potential new medicines to treat serious or life-threatening diseases. If preliminary clinical evidence indicates that a drug may demonstrate substantial improvement over existing therapies on one or more clinically significant outcomes, such as substantial treatment effects observed early in clinical development, it may qualify for the breakthrough designation. Janet Woodcock, M.D., director for CDER (Center for Drug Evaluation and Research) at the FDA, remarked in February that it will be possible to win approval based on expanded Phase 1 clinical data. The benefit to a company of getting the breakthrough designation is a quick review, possibly shaving significant time from this traditionally slow process. "It is one of the most exciting FDA incentives for us at the moment," says Hait. "If you are working on a risky project where you think there is the potential to be substantially better than anything that exists for patients in this area, it gives you an incentive to take that risk." According to Hait, one of the benefits of gaining this designation is the change in the relationship between your company and the FDA — resembling that of a strategic partnership. "The FDA has shown tremendous flexibility in the amount of data you need initially to accelerate getting the drug to patients," he affirms. For example, when ibrutinib first received its breakthrough therapy designation, it was based on Phase 2 clinical data. Such acceleration benefits suffering patients because no longer do they have to wait until the pharmaceutical company completes the traditional three-phase drug development plan to gain access to and potentially benefit from the medication. Hait reminds us that receiving the breakthrough designation does not eliminate the requirement for completing Phase 3 clinical trials and post-marketing analysis, because you still have to show the drug is safe in a large population. Another FDA incentive J&J; capitalized on is related to tropical-disease treatments. As was pointed out previously, TB is a much bigger problem outside the United States. To encourage companies to develop drugs aimed at solving global IS THE BREAKTHROUGH THERAPY DESIGNATION A GOOD THING? When I attended the FDA/CMS Summit last December, the ink was still drying on FDASIA and the FDA's new breakthrough therapy designation. One of the event's speakers, Steven Nissen, M.D., chairman of the department of cardiovascular medicine at the Cleveland Clinic Foundation, said that accelerating a drug's approval should be rare and questioned the thinking behind the FDA's breakthrough therapy designation. Nissen's opinion is in sharp contrast to Janssen's global head of R&D;, Bill Hait, M.D., Ph.D., who describes the policy as being one of the "most exciting" incentives to encourage pharmaceutical companies to be innovative — rewarding those willing to take chances on what would otherwise be highly risky and expensive projects. Why the difference of opinion? After all, both Nissen and Hait are physicians who put patients first. My speculation is as follows. Nissen, a cardiologist, witnessed the debacle when one of the most respected drugmakers in the world, Merck, gained FDA approval for Vioxx, a drug that was eventually pulled from the market after being linked to heart attacks and sudden cardiac deaths. Conversely, Hait has 20+ years of experience in cancer research. I imagine he has witnessed his share of heartbroken families losing loved ones while awaiting cures. Both perspectives are valid. However, I side with Hait and view the breakthrough therapy designation as a good thing. The fact sheet for the process of applying for breakthrough therapy designation is very specific, to the point of requiring that the "REQUEST FOR BREAKTHROUGH THERAPY DESIGNATION," and other points in a company's cover letter and submission to be written "in bold, uppercase letters." This demonstrates the thoroughness with which government agencies leave nothing to chance. So, too, does this language from the FDA: "The Secretary shall, at the request of the sponsor of a drug, expedite the development and review of such drug if the drug is intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development." Time may prove me wrong. But given the parameters the FDA has placed on applying for and obtaining the designation, I don't anticipate this creating a "gold rush" of unnecessary drug approvals. July 2013 LifeScienceLeader.com 21