REMS For Obesity Drugs May Need More Specifics After Qnexa Advisory Panel
Article reprinted from "The Pink Sheet"- July 19, 2010
Providing the details of a risk management strategy would aid sponsors in their quest for a positive response to weight-loss drugs from FDA's Endocrinologic and Metabolic Drugs Advisory Committee, the panel indicated July 15 in its review of Vivus's Qnexa .
The panel opposed approval of the obesity drug by a 6-10 vote, citing the desire for more information about the drug's risk and how the company would prevent its use by those not in the recommended user population - obese patients with a BMI of 30 or more and those with a BMI of 27 or more and weight-related co-morbidities.
Two other obesity drugs are in line for a committee assessment this year. Arena's lorcaserin will go before the panel Sept. 16, and Orexigen's Contrave will follow on Dec. 7.
Vivus went to the Qnexa meeting with the outline of a Risk Evaluation and Mitigation Strategy in hand, including a proposal for a voluntary pregnancy registry. The medication is a fixed combination of phentermine and toparimate, which is a teratogen in several animal species.
Elaine Morrato of the University of Colorado was unimpressed with the company's effort. "It's just very hard as a committee member to assess the sufficiency of the REMS when we only have about seven pages [on the REMS] out of 300 and some pages that talk about all the data and yet we really don't get to see the actual research plan and time."
Before the committee determines if the plan is adequate, it needs to know more details, such as exactly what the company will do to minimize pregnancy, when surveys to assess the effect of the education and communication programs will be conducted and who will be surveyed, she contended.
"It's the kind of detail that I think would be more useful," she said.
"Risk management is a very difficult challenge and we need more information and research on how to really monitor this, control access" to Qnexa, Katherine Flegal, Centers for Disease Control and Prevention, agreed.
The company provided one-year data, yet the drug will be used for a long time, she added, so approving Qnexa would be "like a public health experiment, a large gamble. I think widespread usage in inappropriate populations is difficult to prevent."
Cardiovascular Uncertainties Weigh On Drug
Cardiovascular risk was one of the unknown safety issues surrounding Qnexa for which panel members would have liked more information before approval.
Vivus did not address the issue in its proposed REMS, offering instead to conduct a large cardiovascular outcomes trial.
FDA issued a CV safety warning for Abbott's obesity drug Meridia (sibutramine) in 2009 based on early results from such a trial and FDA expects to ask the panel for input on that drug later this year.
That would be the second time this year for the panel to review post-market safety information for a drug. A joint session July 13-14 with the Drug Safety and Risk Management Advisory Committee resulted in a vote to continue marketing of GlaxoSmithKline's Avandia , which has been under siege because of cardiovascular issues.
Flegler, who sat on the Avandia panel and voted against Qnexa approval, conceded that "my view is colored by Avandia and the safety concerns. We should deal with them before, rather than afterwards."
Life would be easier for obesity drug sponsors if FDA had a clear policy on what is an acceptable risk and when it should be determined for those medications.
Under guidance for assessing CV risk in diabetes, if a meta-analysis of Phase II and Phase III data demonstrates a risk ratio of between 1.3 and 1.8, a drug can be approved if it has an otherwise favorable risk benefit profile, but an outcomes trial may be required. A risk ratio below that is generally accepted as a safe level.
Sanjay Kaul of UCLA asked FDA for its views on the issue, noting that there appears to be an inconsistency if FDA requires CV risk to be ruled out for diabetes drugs but not weight-loss medicines.
Whether to adopt a similar policy has been considered but "we don't have a formal plan" for that, Eric Colman, deputy director of the Division of Metabolism and Endocrinology Products, said.
Given that obesity drugs would be used by a lot of younger patients with type 2 diabetes, he noted, "from a logical standpoint it is something that we would want to discuss. We've had those discussions. It hasn't gotten to the point where we formalized it."
- Cathy Dombrowski
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