On 19th July, the advisory committee to the US Food and Drug Administration (FDA) reviewed a new psoriasis drug from Valeant Pharmaceuticals International Inc. The advisory committee has said that the experimental drug, commercially named as ‘Brodalumab’ should be approved by the FDA as long as measures are taken to mitigate the risk of suicide ideation.
Earlier, the drug use has shown association to suicide ideation in phase 3 clinical trial subjects. Brodalumab belongs to biologic class of drugs that works to treat moderate to severe psoriasis by targeting responsible cell receptors. In this case, the drug blocks the activity of interleukin-17 to help reduce inflammation of skin cells.
The drug was initially developed by AstraZeneca Plc and Amgen, but after the surfacing of first suicide case in May 2015 Amgen pulled out of the partnership. It was in September when Valeant paid $100 million to gain commercial rights to the drug.
The experimental drug had been evaluated in three clinical trials with over 3,000 study participant who showed improvement in the condition after taking the drug. Out of them, six complete suicides were recorded.
The advisory committee comprised of 18 members and 18-0 votes favored the drug approval. Out of them, 14 voted that the drug prescription should be accompanied by strong risk management program and stressed that the precautionary measures should not be restricted to warning label.
Although, FDA is not restricted to always make a decision upon the advisory committee’s recommendation, it typically does so.
Psoriasis is a skin inflammatory disease that takes place due to disrupted cycle of skin cells. As the skin cells divide and build up on to the skin surface, scaly and itchy patches of red skin are observed. It is a chronic disease which may be moderate or severe. Accompanied by irritation and sometimes pain, psoriasis symptoms can often be relieved by the use of anti-inflammatory ointments, oral and/or injectable drugs.
Was A Link Between Brodalumab And Suicide Established?
It was hard for the investigators to understand if the suicide ideation was linked to the drug or not.
The Division of Pharmacoviligance (DVP) of the FDA investigated into this proposed link. According to them, dermatological disorders have an important link to psychological and psychiatric factors. The patients of psoriasis may have a 30-45% possibility to be diagnosed by at least one psychological disorder, according to the Diagnostic and Statistical Manual of Mental Health. Knowing from this information, it is likely for the person to be faced by psychological challenges which have no prior link to the use of the drug.
Amongst the identified psychological disorders, mild depression (dysthymia), major depression and alcohol use disorders were the most common mental problems, while to our surprise 13% of psoriasis patients had a current suicidality.
Researchers went on to learn about any neuropsychiatric adverse effects that might have been elicited by the drug. The analyses were carried out for 12 weeks, were placebo controlled, and were open-label trial phase to document any long term effects. No statistically significant association of the drug with central nervous system or psychiatric problems was recorded. Some mild problems were observed only in a few subjects who had a history of psychiatric or psychological disorders.
A total of 6 suicide cases were reported: four participants from psoriasis study, one from rheumatoid arthritis study and one from psoriatic arthritis study.
These participants were between 39 to 58 years of age who committed suicide at least 14 days after their last dose of Brodalumab. Five of them were identified to have financial or psychosocial stressors and one case was identified to have been caused due to heroin overdose. Out of these, one was also reportedly under legal stress and feared imprisonment.
Because of the nature of the problem, it was hard to determine if the drug should pay the price for the mysterious suicides of the patients. Therefore, the recommendations from DVP suggested that the drug’s packing/bottle should clearly mention the potential risk of suicide ideation. They added that the drug should not be used as the first-line treatment and people with a history of psychiatric disorders should not be restricted from taking the drug, until drug-related risk becomes evident by further studies. Risk management strategies were also recommended to be formulated and delivered timely to the patients.
Over the years, many drugs have been approved to treat psoriasis. The primary goal of these drugs is to stop the uncontrolled growth of skin cells.
Earlier this year, in March FDA approved another psoriasis drug called Taltz. Talz, which is marketed by Indianapolis, Indiana-based Eli Lilly and Company, is found to be effective to reduce the symptoms with only mild side effects. This injectable drug makes use of an antibody that binds to the inflammation inducing protein (interleukin-17A). This drug-protein interaction inhibits the inflammatory response which had otherwise caused the condition.
Tracing back to 2015, two psoriasis drugs were approved by FDA which included Cosentyx from Novartis and Enstilar from LEO Pharmaceticals. Cosentyx also works in the similar manner as Taltz, it releases IgG1 monoclonal antibody to bind and inhibit the signaling of interleukin-17A to cause inflammation. On the other hand, Enstilar works as a vitamin D analog and a corticosteroid (anti-inflammatory) that is applied to the affected parts of the skin in the form of foam. In some cases of exacerbation in condition, it was a highly effective drug.
With an associated risk and better competitor products available in the market, the shares value of Valeant Pharmaceuticals is likely to pay a price. As latest as 19th July, the shares declined by 0.4% to $23.45 after hours.
The final FDA drug approval is expected in November which will influence the fate of Valeant Pharmaceuticals greatly.