SAN FRANCISCO – If just 6 percent of diabetes patients who are obese take Orexigen Therapeutics Inc.'s Contrave (naltrexone SR/bupropion SR), the company will reach $1 billion in sales in short order – assuming the FDA grants approval. Given the agency's action this week, company execs have reason to feel confident.
During his J.P. Morgan Healthcare Conference presentation, CEO Michael Narachi implied the blockbuster status is within easy reach given North American partner Takeda Pharmaceutical Co. Ltd.'s deep inroads with diabetes drug Actos (pioglitazone). Takeda built a strong sales infrastructure for Actos, and "these are the physicians they plan to call on."
Narachi said the FDA's Division of Metabolism and Endocrinology Products just pitched a new resubmission procedure allowing for an interim analysis of the Light Study, the cardiovascular outcomes trial required by the agency for approval of Contrave. It would be the basis of a resubmitted new drug application (NDA) following the 2011 complete response letter based on cardiovascular effect concerns. (See BioWorld Today, Feb. 2, 2011.)
"The FDA recently proposed that, instead of the usual pathway, we can be more efficient," Narachi said. "We can start resubmission with top-line data. It shows inclination [to cooperate and speed drug approvals] and that's a change we've seen [within the FDA] over the last few years."
A complete clinical study report for the interim analysis will be supplied to the FDA during the review within 60 days of the NDA resubmission. The data monitoring committee will conduct the interim analysis after at least 87 major adverse cardiovascular events (MACE) are adjudicated in the Light Study. Timing of the interim analysis depends on the rate of MACE in the Light Study. If the MACE rate is close to the target of 1.5 percent, Narachi said an interim analysis and resubmission of the NDA could come in the second half of 2013. Approval could then come the first half of 2014.
"2013 is going to be a pivotal year," he said. "We also plan a European submission this year."
Narachi's confidence related to quick and massive uptake of the drug is based on a belief that the landscape for treating obesity is changing dramatically. As he said, it's being "medicalized." Many forces are combining – political, socio-economic, personal – and multifactorial approaches are being tried.
Opening the potential market wider are governments, like the UK, which are getting into the carrot and stick act when it comes to obesity and related comorbidities.
"In the UK, people in indigent programs for housing and food who are not compliant with weight loss programs may get lower [assistance] payments," he said.
And the fact that there are several other competitors hitting the market at the same time, such as Vivus Inc.'s Qsymia (phentermine/topiramate) and Arena Pharmaceuticals Inc.'s Belviq (lorcaserin) isn't daunting to Narachi, Orexigen or Takeda.
"This is not a share fight," Narachi said. "This is a grow-the-market game. With two other new entrants, there are a lot of positive things happening. The major driver is a dramatic increase in the cost of health care. . . . Obesity is at the heart of this. Recognition of this is growing."
Light study progress "has been phenomenal. We were given a very high hurdle," he said, adding that enrollment has already reached 9,000 patients.
The company also discussed plans to start the Ignite Study, a randomized open-label clinical trial designed to yield more data related to the real-world weight loss potential of Contrave when combined with a comprehensive lifestyle intervention program vs. usual care. Orexigen will initiate randomization of about 200 patients into the Ignite Study later this quarter.
Ignite is a method-of-use trial, intended to demonstrate how the drug should be used, who it's for and why patients should try it. It will enroll "typical" patients who have a willingness to change, Narachi said. "We expect 10 percent to 15 percent weight loss for the Contrave arm."
J.P. Morgan analyst Cory Kasimov said that latest regulatory update is favorable and in line with expectations. "OREX has continued to navigate smoothly through the initial regulatory setback, and we anticipate approval next year after a cardiovascular risk is ruled out by the interim analysis of the Light study," Kasimov wrote.
Mark Booth, Orexigen's chief commercial officer, is prepping for the anticipated approval: "Our launch will be fundamentally different. We're going out big right from the get go. Nothing incremental."
Hence, the projected warp-speed rocketing to the $1 billion mark.
Orexigan's stock (NASDAQ:OREX) held steady Monday afternoon when the news first hit and then dipped slightly on Tuesday, losing 8 cents to close at $5.94.