On Wednesday, the U.S. FDA advisory panel concluded that the benefits of Johnson & Johnson’s experimental rheumatoid arthritis drug Sirukumab do not outweigh the risks.
The FDA has therefore snubbed the safety profile of the Johnson & Johnson (J&J)-sponsored rheumatoid arthritis (RA) candidate sirukumab, even though the drug’s efficacy was found sufficient for authorization.
The panel voted 12-1 that the drug should not be approved, citing safety concerns, including an imbalance in the number of deaths in patients taking sirukumab compared with those taking a placebo. The most common causes of death were major heart problems, infection and malignancies.
“The safety is not there,” said Dr. Beth Jonas, interim head of the division of rheumatology at the University of North Carolina School of Medicine.
Since the FDA is not obliged to act on the recommendation of its advisory panels, J&J went into the meeting needing to convince the FDA arthritis advisory committee to downplay the significance of the imbalance in mortality seen in clinical development. Of the 35 deaths that occurred within 16 weeks of the last dose, 34 involved patients who received sirukumab. The FDA saw the main causes of death—cardiovascular disease and serious infections—as indicative of immunosuppressive effects
. And J&J ultimately failed to shake this worry from the experts’ minds.Sirukumab blocks a cytokine in the body known as interleukin 6 (IL-6) that can contribute to the inflammation associated with rheumatoid arthritis, an autoimmune disorder that affects more than 1.3 million. J&J originally developed the drug with GlaxoSmithKline Plc. GSK recently said it would return all rights to J&J. GSK held rights to the drug in North, Central and South America.
The mortality imbalance recurred repeatedly in the expert’s explanations of their “no” votes. The prospect of clearing a drug linked to increased mortality for use in patients with moderate to severe rheumatoid arthritis who had tried one disease-modifying antirheumatic drug proved too much for most panelists, despite their belief in its efficacy.
The 12 “no” votes on the safety and approval questions followed 13 “yes” votes on the efficacy question.
“We are disappointed and disagree with the group’s interpretation of the sirukumab benefit-to-risk profile,” Newman Yeilding, M.D., head of immunology development with J&J’s Janssen R&D, said yesterday in a company statement. “We remain confident in the data accumulated to date supporting sirukumab in the treatment of moderately to severely active RA. We look to continue discussions with the FDA in their review of the application as we believe sirukumab represents an important therapeutic option for patients with RA.”
Panelists said they were especially reluctant to recommend approval of sirukumab because there are two other drugs on the market in the same class. These are Roche Holding AG’s Actemra and Sanofi SA and Regeneron Pharmaceuticals’ Kevzara.
“If this was a new agent I would probably be a little more enthusiastic,” said Dr. Maria Suarez-Almazor, rheumatology section chief at the University of Texas MD Anderson Cancer Center. “There is no reason to think that this new drug will act in a tremendously different way.”
