SAN DIEGO ( TheStreet) -- Orexigen Therapeutics ( OREX) has legitimate reasons to feel good about restarting development of its rejected obesity drug Contrave, but let's be realistic -- the "clear and feasible" path to approval is still long, expensive and pockmarked with risk. To convince the U.S. Food and Drug Administration to approve Contrave, Orexigen and its Japanese partner Takeda need to run a 10,000-patient safety study to assess the heart-safety risk of the obesity drug. Orexigen negotiated some concessions out of FDA to make this safety study easier (more on that below) but enrolling 10,000 patients in a single study will be a colossal and difficult undertaking. Consider this: Orexigen conducted four phase III studies of Contrave totaling 4,500 obese patients to generate the clinical data needed to submit the drug for FDA approval the first time around. These phase III studies took approximately 13 months to fully enroll. Now, Orexigen has to enroll approximately 10,000 patients -- more than double the number of patients in all four of its previous phase III studies combined. Orexigen plans to start the Contrave safety study in the first half of 2012. If all goes well, the drug could be approved in 2014, the company claims. Two-plus years to enroll 10,000 patients, conduct a study, crunch the data (hopes it's positive), re-submit to FDA (which will almost certainly hold another advisory panel) and then receive approval? Really? Isn't three or four years more realistic? A more conservative timeline could have Contrave approved in 2015 or 2016. How big is a 10,000-patient study? Consider that FDA also required BioSante Pharmaceuticals ( BPAX) to conduct a safety study of its low-dose testosterone gel LibiGel which is enrolling only 3,500 patients. By the way, the BioSante study began in January 2008 and is still not finished. At my request, the analysts at Sagient Research, the research firm behind BioMedTracker, went through their databases to identify all clinical trials (completed and ongoing) that enrolled more than 9,000 patients. Of the thousands of clinical trials reviewed by Sagient, only 168 studies enrolled more than 9,000 patients. Drug companies are responsible for just 74 of those 168 large studies -- meaning the studies weren’t sponsored or run by government-funded health agencies or universities.
Abbott Labs ( ABT) is the only drug company to run an outsized obesity clinical trial. That was the long-term safety study of Meridia and it didn't turn out well. Meridia was yanked from the market because this study linked the drug to unacceptable safety risks. Needless to say, Orexigen has no experience running a 10,000 patient study. Nor does Takeda, by the way. Orexigen is on the hook to pay for the entire cost of the Contrave safety study, unless the company can re-negotiate the terms of its partnership with Takeda. Orexigen needs $100 million to pay for the study. The company has $70 million in the bank. The reason FDA is demanding a pre-approval safety study is because the phase III program showed Contrave increased pulse and blood pressure. These are the same cardiovascular risk factors that ultimately killed off Meridia. Initially, FDA wanted Orexigen to run a safety study that would essentially rule out the possibility that Contrave caused any increase in heart attacks, strokes or other cardiovascular adverse events. Such a study could have required enrolling 100,000 patients! Orexigen complained and appealed FDA's decision -- and rightly so. FDA ultimately conceded and lowered the risk threshold by which Contrave will be judged. According to Orexigen, Contrave could still be approved if it increased the relative risk of heart attack, stroke and other heart-related safety events by about 30% over placebo. That's a nice win for Orexigen and it may help the company to ultimately see its long-delayed and embattled obesity drug reach the market. But investors should not under-estimate the enormous challenge that lies ahead for Orexigen and Contrave (not to mention the other obesity drug players Vivus ( VVUS) and Arena Pharmaceuticals ( ARNA)) despite what looks like good news Tuesday. --Written by Adam Feuerstein in Boston. >To contact the writer of this article, click here: Adam Feuerstein. >To follow the writer on Twitter, go to http://twitter.com/adamfeuerstein. >To submit a news tip, send an email to: firstname.lastname@example.org.