New Challenges for Johnson and Johnson: Biosimilars Erode Remicade Sales, Sirukumab Receives CRL

Kelly Davio

The FDA has issued a complete response letter (CRL) for Johnson and Johnson’s proposed rheumatoid arthritis (RA) drug, sirukumab. Janssen Biotech, a division of Johnson and Johnson, had filed a Biologics License Application (BLA) for the interleukin-6 (IL-6) inhibitor, including data from a global phase 3 clinical development program, in September 2016.

The FDA has issued a complete response letter (CRL) for Johnson and Johnson’s proposed rheumatoid arthritis (RA) drug, sirukumab. Janssen Biotech, a division of Johnson and Johnson, had filed a Biologics License Application (BLA) for the interleukin-6 (IL-6) inhibitor, including data from a global phase 3 clinical development program, in September 2016.

“We are disappointed by this development as we feel the data accumulated to date support the efficacy and safety of sirukumab in the treatment of moderately to severely active rheumatoid arthritis,” said Newman Yeilding, MD, head of immunology development for Janssen. “We believe sirukumab represents an important therapeutic option for patients living with rheumatoid arthritis, especially for those individuals who cycle through multiple treatments and continue to struggle to find an effective option for a potentially disabling disease.”

The CRL for sirukumab does not come as a surprise to the rheumatology world; the FDA’s rejection of the drug follows an August 2, 2017, Arthritis Advisory Committee (AAC) meeting in which the voting committee members did not recommend drug approval. The AAC expressed concerns about 35 patient deaths reported during a phase 3 clinical program in patients with RA, 34 of which occurred in the sirukumab arm of the study. The most common causes of death included major cardiac adverse events (AEs), infection, and malignancy.

Sirukumab was also associated with laboratory abnormalities (decreased neutrophil count; increased liver function test values; and increased lipid parameters, including low-density lipoprotein, high-density lipoprotein, and triglycerides). These abnormalities were documented with both the 50-mg and 100-mg doses of sirukumab that were studied.

Janssen has been among several companies seeking to retain a hold on the increasingly crowded RA marketplace in the face of increasing biosimilar competition for an established biologic as its innovator infliximab (Remicade). By developing an IL-6 inhibitor for use in patients who had not had an adequate response to such products as Remicade, Janssen had likely hoped to buffer itself against further erosions of its sales from infliximab biosimilars Inflectra and Renflexis. With sirukumab’s rejection by the FDA, Janssen lags behind such approved IL-6 drugs as sarilumab (manufactured by Sanofi) and tocilizumab (Acterma) manufactured by Roche).

Janssen said that it would review the details of the CRL and create a plan for follow-up discussions of the drug’s rejection with the FDA. The company hopes to, as Yeilding said, “Gain a full understanding of FDA requirements for US approval.”