Following rejections earlier this year of two previous anti-obesity drugs, the FDA’s Endocrinologic and Metabolic Drugs advisory committee recommended approval for Contrave, the combination of sustained release forumulations of naltrexone and buproprion from Orexigen Therapeutics.
The committee voted 13-7 in favor of the drug, saying that the benefits of Contrave outweighed its risks. The committee voted 11-8 that the company should conduct a large safety trial following approval of the drug. The same panel voted against recommending approval for lorcaserin (Arena) and Qnexa (Vivus) earlier this year.
Sanjay Kaul, who was a panel member and who voted against approval, provided the following comment to CardioBrief:
The drug does not yield a weight loss efficacy margin that allows an acceptable safety trade-off consideration, especially given the adverse blood pressure and heart rate signals. When you couple that with a selective low-risk patient population (which is arguably not representative of the intended use of the drug in the real world), and the short-term exposure, the benefit-risk assessment becomes even more challenging. The drug resembles sibutramine (meridia), both in terms of its modest efficacy and cardiometabolic profile and blood pressure and heart rate signals. Meridia was withdrawn from the US market based on the results of the SCOUT trial which revealed an increased cardiovascular risk. There is an opportunity for us to learn from history, or else we are likely to repeat it. Every time the regulator agency withdraws a product from the market, undoubtedly driven by its core mission to ensure public safety, there is a price to pay for it – erosion of public trust. We need to make sure that we get it right the first time. Providing a more emancipated guidance to the industry that captures the true benefit-risk of weight loss intervention in its intended environment will help them navigate these stormy waters.
In a followup note, Kaul made it clear that, despite the final vote, he believes the panel could hardly be said to have endorsed Contrave, suggesting that the road to approval may still contain a few rocks:
The Contrave panel is yet another example of the disconnect between vote and discussion. If the vote for pre-approval CV trial was 8 to 11, and two voters who voted for a post-approval CV trial voted against approving the drug, then logic dictates that the count should be 11 to 9 in favor of approval, not 13-7. If anyone could discern from the comments, even those who voted for drug approval, an endorsement for the drug, then maybe I was at a different meeting. The 13-7 vote is going to create a buzz in the press reports and not accurately reflect the tepid enthusiasm for this drug.
Here is the Orexigen press release:
|Orexigen(R) Therapeutics’ Investigational Drug Contrave(R) Receives Positive Recommendation from FDA Advisory Committee for Treatment of Obesity|
|SAN DIEGO and OSAKA, Japan, Dec. 7, 2010 /PRNewswire via COMTEX/ —
Orexigen(R) Therapeutics, Inc. (Nasdaq: OREX) and Takeda Pharmaceutical Company Limited (Takeda) (TSE:4502) announced today that the U.S. Food and Drug Administration’s (FDA) Endocrinologic and Metabolic Drugs Advisory Committee voted 13 to 7 that the available data adequately demonstrate that the potential benefits of Contrave(R) (naltrexone sustained release (SR)/bupropion SR) outweigh the potential risks when used long-term in a population of overweight and obese individuals and support approval. The Committee also voted 11 to 8 that a dedicated study to examine the drug’s effect on risk for major adverse cardiac events should be conducted as a post-approval requirement versus pre-approval.
“We are encouraged by the panel’s view of the risk-benefit profile of Contrave,” said Michael Narachi, president and CEO of Orexigen. “We look forward to continued discussions with the FDA regarding the design of a post-marketing study to evaluate cardiovascular risk and to address the questions raised at the meeting today in preparation for our PDUFA action date in January.”
The advisory committee’s decision is a non-binding recommendation to be considered by the FDA in finalizing the review of the Contrave New Drug Application (NDA). A PDUFA action date of January 31, 2011 has been assigned for the review of the NDA.
“We are pleased with today’s committee vote, an important step on the path to approval for this potential new option for the treatment of obesity and an example of the dedication of the Orexigen-Takeda team,” said Shinji Honda, president and CEO of Takeda Pharmaceuticals North America, Inc., a wholly-owned subsidiary of Takeda. “Takeda is committed to working to provide new treatment options in managing obesity and helping physicians address this growing epidemic. We believe Contrave, if approved, could be an important addition to the limited therapeutic options currently available.”
Orexigen management will host a call and webcast to discuss this update tomorrow, December 8, 2010, at 4:15 p.m. Eastern time. The live call may be accessed by phone by calling (866) 510-0712 (domestic) or (617) 597-5380 (international), participant code 63015455. The webcast can be accessed live on the investor relations section of the Orexigen web site at www.orexigen.com and will be archived for 14 days following the call.
Contrave is an investigational combination therapy for the treatment of obesity. The two components of this combination therapy, naltrexone SR and bupropion SR, appear to act in a complementary manner in the central nervous system and are believed to address both biological and behavioral drivers of obesity.
About Orexigen Therapeutics
Orexigen Therapeutics, Inc. is a biopharmaceutical company focused on the treatment of obesity. Further information about the Company can be found athttp://www.orexigen.com.
About Takeda Pharmaceutical Company Limited
Located in Osaka, Japan, Takeda is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company inJapan and one of the global leaders of the industry, Takeda is committed to strive towards better health for patients worldwide through leading innovation in medicine. Additional information about Takeda is available through its corporate website, www.takeda.com.
About Takeda Pharmaceuticals North America, Inc. and Takeda Global Research & Development Center, Inc.
Based in Deerfield, Ill., Takeda Pharmaceuticals North America, Inc. and Takeda Global Research & Development Center, Inc. are subsidiaries of Takeda Pharmaceutical Company Limited, the largest pharmaceutical company in Japan. The respective companies currently market oral diabetes, insomnia, rheumatology and gastroenterology treatments and seek to bring innovative products to patients through a pipeline that includes compounds in development for diabetes, cardiovascular disease, gastroenterology, neurology and other conditions. To learn more about these Takeda companies, visitwww.tpna.com.
Forward-Looking Statements Related to Orexigen
Orexigen cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. Words such as “believes,” “anticipates,” “plans,” “expects,” “indicates,” “will,” “intends,” “potential,” “suggests,” “assuming,” “designed” and similar expressions are intended to identify forward-looking statements. These statements are based on the Company’s current beliefs and expectations. These forward-looking statements include statements regarding the potential for, and timing of, approval for Contrave, the potential for, timing of and design of a post-approval study to evaluate safety risks, and the Company’s belief that this product candidate may be an important therapeutic option in the treatment of obesity. The inclusion of forward-looking statements should not be regarded as a representation by Orexigen that any of its plans will be achieved. Actual results may differ from those set forth in this release due to the risk and uncertainties inherent in the Orexigen business, including, without limitation: the uncertainty of the FDA approval process and other regulatory requirements; the uncertainty of the process with FDA to agree on and finalize a design for a post-approval study to evaluate safety risks; the therapeutic and commercial value of Contrave; reliance on third parties to assist with the development of Contrave; and other risks described in the Company’s filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Orexigen undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. Further information regarding these and other risks is included under the heading “Risk Factors” in the Company’s Quarterly Report on Form 10-Q, which was filed with the Securities Exchange Commission on November 4, 2010 and is available from the SEC’s website (www.sec.gov) and on our website (www.orexigen.com) under the heading “Investor Relations”. All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.
Forward-Looking Statements Related to Takeda
This press release contains forward-looking statements regarding the Company’s plans, outlook, strategies, and results for the future. All forward-looking statements are based on judgments derived from the information available to the Company at this time. Forward looking statements can sometimes be identified by the use of forward-looking words such as “may,” “believe,” “will,” “expect,” “project,” “estimate,” “should,” “anticipate,” “plan,” “continue,” “seek,” “pro forma,” “potential,” “target,” “forecast,” or “intend” or other similar words or expressions of the negative thereof. Certain risks and uncertainties could cause the Company’s actual results to differ materially from any forward looking statements contained in this press release. These risks and uncertainties include, but are not limited to, (1) the economic circumstances surrounding the Company’s business, including general economic conditions in the US and worldwide; (2) competitive pressures; (3) applicable laws and regulations; (4) the success or failure of product development programs; (5) decisions of regulatory authorities and the timing thereof; (6) changes in exchange rates; (7) claims or concerns regarding the safety or efficacy of marketed products or product candidates; and (8) integration activities with acquired companies.
SOURCE Orexigen Therapeutics, Inc.