FDA Requests Additional Manufacturing Information for High-Dose Spinraza, Delaying Approval

Biogen faces an unexpected setback in its pursuit of approval for a high-dose regimen of Spinraza (nusinersen) in spinal muscular atrophy (SMA) patients. The U.S. Food and Drug Administration (FDA) has issued a complete response letter (CRL) to the company, requesting updates to technical information in the chemistry, manufacturing, and controls portion of the application.

Biogen's Response and Resubmission Plans

Despite the setback, Biogen remains optimistic about the potential of high-dose Spinraza. Priya Singhal, M.D., head of development at Biogen, stated, "While this outcome was unexpected, we remain committed to bringing the high dose regimen to people living with SMA. We are working diligently to provide the necessary information to the FDA."

The company plans to resubmit its application "promptly," emphasizing that the FDA's rejection did not cite any issues with the clinical data supporting the high-dose regimen. Biogen noted that the FDA "provided options for resolution," suggesting a path forward for the company.

High-Dose Spinraza: Potential Benefits and Clinical Data

The proposed high-dose regimen for Spinraza involves two 50-mg starter doses given 14 days apart, followed by a 28-mg maintenance dose administered monthly. This is a significant increase from the currently approved regimen, which uses 12-mg doses.

Biogen's pursuit of the high-dose option is supported by positive results from its phase 2/3 Devote trial. In the Part B portion of the study, the higher dose regimen demonstrated significant improvements in SMA patients' mobility, as measured by the Children's Hospital of Philadelphia-Infant Test of Neuromuscular Disorders (CHOP-INTED).

The company has also released data suggesting that higher-dose Spinraza could benefit a range of SMA patients, including those who haven't been treated previously and those with early- and late-onset disease.

Broader Context: Manufacturing Challenges in SMA Therapies

Biogen's Spinraza setback is not isolated in the SMA treatment landscape. On the same day, Scholar Rock announced that the FDA had rejected the application for its SMA candidate apitegromab due to manufacturing issues. The rejection was related to findings during an inspection of a third-party manufacturing site in Indiana, which was not specific to Scholar Rock's monoclonal antibody candidate.

These developments highlight the increasing scrutiny on manufacturing processes in the pharmaceutical industry, particularly for complex biologics and gene therapies used in treating rare diseases like SMA.