Orexigen On Quicker-Than-Expected Pace To Obtain Data Needed To Re-File NDA For Contrave
This article was originally published in The Pink Sheet Daily
Executive Summary
During its second quarter earnings call, the biotech said it sees recent FDA approvals of two other obesity drugs as a positive for its own prospects, but it is re-engaging with the agency on why it must perform a cardiovascular-outcomes trial prior to approval.
Recent FDA approvals of Vivus Inc.’s Qsymia (phentermine/topiramate) and Arena Pharmaceuticals Inc.’s Belviq (lorcaserin) are positives for Orexigen Therapeutics Inc. and its pipeline of two novel drugs for obesity, President and CEO Mike Narachi said during an investor call Aug. 7.
The company is continuing with a cardiovascular outcomes trial it must conduct in order to re-file an NDA for its lead compound, Contrave, but it also is asking FDA why the other two drugs were approved without that same pre-approval data.
Enrollment in the Light Study, a 10,000-patient cardiovascular outcomes study Orexigen negotiated with FDA after receiving a “complete response” letter in 2011 for Contrave (naltrexone sustained release/bupropion sustained release), is proceeding faster than expected, which has enabled the company to shorten its projected timeline to re-filing and potential approval (Also see "With SPA Finalized, Orexigen To Begin CV Outcomes Study For Contrave In Second Quarter" - Pink Sheet, 6 Feb, 2012.). Orexigen can re-submit its NDA following an interim data analysis that will be triggered by the 87th major adverse cardiovascular event (MACE) in the trial.
In July, the San Diego-based firm reported that it already had enrolled more than 1,500 patients at roughly 100 sites, with an expectation of activating the trial’s remaining 200 sites by the end of August. That enrollment pace meant Orexigen expected to complete enrollment in the first half of 2013 and reach the necessary MACE threshold during the second half of 2013, nearly cutting in half the projected time to re-submission of the NDA (Also see "Orexigen Agreement On Contrave CV Trial Hints At FDA’s Thinking On Obesity" - Pink Sheet, 26 Sep, 2011.).
During the Aug. 7 call to report second quarter financial results, Narachi said Orexigen had entered planning for Light having been warned that enrollment could take up to three years and require international sites, as well as locations in the U.S. The company reviewed historical data from previous trials, however, and determined that it could take steps to speed up enrollment, he said.
“We saw enrollment as something that was in our control and [believed we] could speed the time to the interim analysis and potential approval of Contrave,” he said. “Once we established our plans, we believed a reasonable estimate for enrolling the study would be 18 to 20 months.”
With its July announcement, Orexigen is exceeding its own projections, the CEO noted.
“Since the last update, we have activated an additional 90 sites and our prediction that we would achieve our enrollment goal in the first quarter of next year was predicated on the expectation that recruitment would slow down from the initial surge of patients,” Narachi said. “To date, enrollment has not slowed down, although we’re not yet ready to update guidance on when enrollment will be complete.” For now, the company is maintaining its expectation of reaching the interim analysis in the second half of 2013, which could mean an FDA approval early in 2014, he added.
First-Mover Advantage Still Up For Grabs
FDA approved Arena’s Belviq, the first new obesity drug approval in more than a decade, on June 27, but launch has been delayed because the Drug Enforcement Administration must determine whether to list the drug as a Schedule IV controlled substance (Also see "Belviq Gains FDA Approval For Weight Loss, But DEA Review Will Delay Launch" - Pink Sheet, 27 Jun, 2012.). This expected four-to-six month delay gives the potential of a first-mover advantage to Vivus, whose Qsymia (formerly called Qnexa) was approved July 17. Vivus hopes to launch the product in the fourth quarter of this year (Also see "FDA Approves Vivus’ Obesity Drug, Recommends Against Use In High-Risk Heart Patients" - Pink Sheet, 17 Jul, 2012.).
Around the time Orexigen announced its enrollment progress for the Light Study, Leerink Swann & Co. analyst Marko Kozul issued analysis that was bullish on Contrave’s chances of approval. Rating the company’s stock “outperform” in a July 16 note, Kozul also reported that feedback from key opinion leaders indicated Contrave would perform in the middle of the three new obesity drugs if approved.
Qsymia would claim the leading market share based on rapidity of effect, most significant weight loss seen in clinical trials and continued weight loss seen after one year of treatment, he wrote. Belviq would claim the smallest share because of the lowest amount of weight loss and weight gain seen after one year, but the drug might have longer-term potential in combination therapy with phentermine, Kozul said. Contrave would offer better efficacy than Belviq, although not as good as that for Qsymia, and would be differentiated based on its potential for weight loss in patients with craving-associated disease, he added.
On July 18, after the approval of Qsymia, Kozul raised his North American sales guidance for Contrave in the 2016-2018 term to $380 million, $570 million and $740 million in each of those years. “We continue to believe the public will have an appetite for relatively higher-priced obesity drugs, and eventually third-party payers are likely to provide reimbursement,” he wrote. “We also believe approval of multiple innovative obesity drugs should expand the obesity market.”
During the call, Narachi said Orexigen is updating its 2010 market research but believed then as now that “a rising tide would lift all boats.” Orexigen is poised to benefit from a “positively changing regulatory environment” indicated by the two recent FDA approvals, he said.
After initial launch, Orexigen’s challenge will be to build the obesity market beyond the 10,000 to 15,000 current frequent prescribers of obesity drugs, Narachi said. “[It] will take some time but health care providers are eager to have an effective means of addressing obesity,” he predicted.
Primary Care Doctors Key To Growing Market
The goal will be to get the 90,000 primary care doctors who actively treat co-morbidities of obesity to include obesity drugs in their therapeutic armamentaria. “We believe that treating obesity will soon become a cornerstone of cardio-metabolic care and physicians will begin to prescribe obesity therapeutics as a critical and complementary step towards preventing and treating diabetes, managing hypertension and improving lipid profiles,” Narachi explained.
A key to achieving that goal will be to increase awareness that even modest weight loss can translate into important long-term health benefits, he said. “Three novel obesity therapeutics launching over the next couple of years will supply a level of resources needed to drive education, awareness and successful adoption,” Narachi said.
While Orexigen welcomed the approvals of Qsymia and Belviq, those decisions by FDA raised the question of why they could be approved without cardiovascular outcomes trials, but Contrave could not, he added.
“It’s a very good question and it’s a question that I can tell you I am very determined to get an answer to,” he said. “We have reengaged with the agency since the recent approvals … and are seeking whether there is a possible shorter path to approval or something that is improved from our current path.”
Beyond Contrave, Orexigen also has advanced a second obesity candidate, Empatic (bupropion sustained release/zonisamide sustained release) through Phase II, in which it demonstrated weight loss up to 9.9% after six months of treatment. The company waited to design its Phase III program until FDA made a regulatory decision on Qsymia, because that drug includes topiramate, an anti-convulsant like zonisamide. Now that Qsymia has cleared FDA’s safety review, Orexigen plans to meet with the agency later this year to determine Phase III protocols for Empatic, Senior VP and Head of Global Development Preston Klassen said.