FDA Raises Safety Concerns for Valeant’s Psoriasis Therapy Drug
FDA reviewer’s on preliminary assessment revealed that Valeant’s Psoriasis drug, Brodalumab carries potential suicide risk which is being difficult to assess due to unavailability of adequate data.
The assessment was posted ahead of the original review meeting which is to be held on 19th July. The fate of the drug will be decided after the opinion given by FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee. The drug is awaiting FDA approval from January 2016.
Valeant Pharmaceuticals’ Brodalumab is an experimental drug which is being developed for the treatment of the moderate to severe psoriasis (form of skin disorder). Psoriasis is a long-term autoimmune disease characterized by red, itchy and scaly patches of abnormal skin.
Brodalumab is a human monoclonal antibody (immunoglobulin G2) which binds to interleukin-17 receptor and act as inhibitor by seizing all the biological activities. The drug is designed to be administered in subcutaneous region which will be present in prefilled syringes in standard doses(mg/ml) to be administered in 0, 1 and 2 weeks to the patients who are eligible for systemic and phototherapy after diagnosis of the disease.
Figure 1. Molecular mechanism of brodalumab (photo credit: Nature Reviews Drug Discovery 12, 815–816 (2013) doi:10.1038/nrd4152).
The efficiency of the drug was tested by 3 pivotal Phase III clinical trials which included ustekinumab comparator arm in two of the trials. Patients of age group 18- 75 years, suffering from severe to moderate psoriasis were enrolled. According to the preliminary reports of FDA the drug was highly effective against psoriasis in comparison to placebo results as per PASI (Psoriasis Area and Severity Index) and static Physician’s Global Assessment (sPGA). During the trials total of 6 completed suicides were reported; 4 in late stage clinical studies (psoriasis) and two from previous trials (one in rheumatoid arthritis and one in psoriatic arthritis). One was later informed due to drug overdose. All of these incidents made Valeant pharmaceuticals to abruptly halt the trials thereby preventing further evaluation of the drug.
This raised concerned from the FDA reviewers on the questionable safety of the drug. Reviewers also hypothesized that an increase level of IL-17 may increase other cytokines level thus causing increase in major adverse cardiac events (MACE).
The reports of FDA staff stated “The biologic effects of the resulting increase in serum IL-17A and its interaction with other cytokines are not well understood; however, the available data raise concerns about a potential interaction with cytokines in the central nervous system and an impact on cardiovascular atherosclerosis. Limited controlled data in the brodalumab development program for these uncommon events makes the assessment of risk–benefit for brodalumab challenging.”
Brodalumab was developed by Amgen. Later Amgen in collaboration with AstraZeneca showed promising clinical results of the compound. In May 2015, Amgen moved out of the collaboration due to its link between the suicide of 6 patients which halted its further trial. Later in September, AstraZeneca partnered with Valeant which gave it exclusive rights to develop and commercialize brodalumab.
Brodalumab’s potential approval will come with lots of warning and precautions starting with Risk Evaluation and Mitigation Strategies (REMS) label warnings or black box warnings. All these stipulations are surely going to lower the chance of successful commercialization of the drug.
There are already some next-generation psoriasis drugs available in the market like Novartis’ Cosentyx and Eli Lilly’s Taltz. So, approval or not either way the times are tough for Valeant’s brodalumab.
Featured image credit: Graphics remixed by Medgenera.com. test-tubes set on the rack in doctor hands © IvaKem (Stock Photo ID: 97721096)