Suicide Warnings For Valeant’s Siliq Could Hinder Access To Psoriasis Treatment
Executive Summary
While an FDA advisory committee unanimously supported approval of the plaque psoriasis drug brodalumab, several recommended a black box warning on suicide risk that could limit sales of the drug.
The variety of strict safety recommendations from the FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee could have the unintended consequence of limiting access to Valeant Pharmaceuticals International Inc.’s plaque psoriasis candidate Siliq (brodalumab), should it reach the market.
Although all 18 panelists recommended the treatment for approval, several said they would only support the FDA’s backing if the labeling for the drug includes a black box warning for the potential drug-related risk of suicide ideation and behavior.
Suicidal ideation and behavior was the primary focus of discussion during the meeting. There were six completed suicides in brodalumab's clinical development program, raising questions about whether there was a drug-related risk. (Also see "Valeant's Siliq Clears FDA Panel But Faces Prospect Of Post-Marketing Registry" - Pink Sheet, 19 Jul, 2016.) Committee Chairman Michael Bigby and patient representative Elizabeth Smith were among the panelists calling for a black box warning.
But other members cautioned of such strict measures with concerns that they may prevent the drug from getting to patients who need it. Panelist Matthew Rudorfer, chief of the somatic treatments and psychopharmacology program at the National Institute of Mental Health, warned that strict post-marketing measures could scare people away from using and prescribing what he called an effective drug.
Analysts had mixed reviews about Siliq’s commercial potential if approved with a black box warning. Raghuram Selvaraju of investment bank Rodman & Renshaw Capital Group said in a research note that the treatment could generate between $400m and $500m in sales despite a black box warning if approved, pointing to its “solid efficacy.”
Conversely, TD Securities Inc. analyst Lennox Gibbs gave a more grim assessment of a black box warning. He said in a note that such a warning would be one of the most damaging components to patient access and sales.
Exacerbated By REMS?
Gibbs also cited a mandatory registry as a crippling aspect of sales and patient access.
Fourteen of the panelists supported approval for Siliq only if risk management options beyond labeling, such as a Risk Evaluation and Mitigation Strategy, were implemented to address suicidal ideation and behavior. Many of these members called for a mandatory registry as part of a REMS.
Valeant consultant Mark Lebwohl appeared to have confirmed fears that suicide warnings would hinder patient access to the drug. Lebwohl, who is a professor of dermatology at the Icahn School of Medicine at Mount Sinai, said during a conversation about a registry that he would not prescribe the drug to patients who he feels are at risk of suicide, such as patients with depression.
“If a patient came to me and I was worried about suicide in that patient, there is no way they would be getting this drug,” Lebwohl said. (Also see "Post-Marketing Registry, Suicidality Warning Could Be Paradox For Siliq" - Pink Sheet, 21 Jul, 2016.)
Michael Irwin, a professor of psychiatry and biobehavioral sciences at the David Geffen School of Medicine at UCLA, suggested the drug include in a warning that suicides can occur without a patient necessarily showing symptoms of anxiety and depression. That phrasing could discourage physicians from using the drug even in patients without a history of depression.
“Clinicians need to be aware that this is not a suicide that is just going to occur within the subject of depression,” Irwin said. “It might come out of the blue, so to speak, and be impulsive.”
Irwin was among the 14 panelists who backed approval for Siliq only if FDA instituted risk management beyond labeling, including a mandatory registry. He did not, however, specify that his warning should be a black box.
Valeant officials tried to downplay the risk of suicide posed by the drug. They noted that most of the suicides occurred due to circumstances outside of depression. For example, one of the subjects was about to go to jail, while another had lost his disability payments.
The Canadian drug maker added that depressive symptoms had worsened in the placebo group more than in patients taking Siliq.
FDA has until Nov. 16 to make a decision on the drug. Originator Amgen Inc. dropped the drug after the suicide issue came to light, and former partner AstraZeneca PLC subsequently licensed brodalumab to Valeant.