SPINRAZA: An Exemplary Development Path for Gene Therapies to Follow

SPINRAZA was recently featured in a publication preview in Gene Therapy titled, “Development of gene therapies – lessons from nusinersen.” In the article, author Dr. Billy Dunn, Director of the Office of Drug Evaluation in the Division of Neurology Products, and colleagues at the U.S. Food and Drug Administration (FDA) discuss how SPINRAZA, an antisense drug discovered by Ionis Pharmaceuticals, using its proprietary technology, and co-developed by Ionis and Biogen, is an excellent example for the development and regulatory pathway for gene therapies for severe and life-threatening diseases. SPINRAZA’s development path led to a broad approval by the FDA in record-breaking time, and is now also approved in the EU, Canada and Japan. Lessons from the SPINRAZA experience underscore the importance of rigorous and flexible clinical study design and an ongoing, collaborative effort with regulators.

The SPINRAZA Phase 3 program, including two randomized, double-blind, sham-controlled studies in two subpopulations of spinal muscular atrophy, demonstrates that comprehensive, well-designed and controlled Phase 3 studies, which provide compelling evidence, may enable a faster path to marketing approval. The inclusion of a sham-controlled arm was an important component of the SPINRAZA Phase 3 program and regulators often recommend including concurrent controls with appropriate blinding to decrease concerns regarding bias in the study results. Furthermore, as seen with SPINRAZA’s overall development program of two controlled studies and five open-label studies, complementary clinical studies providing additional evidence of safety and effectiveness may be necessary for approval and can be supportive of a broad label. Ionis and Biogen’s experience working closely with regulators emphasize that regular and collaborative communication can facilitate agreement upon development strategy and in turn enable an efficient and rapid review process. Additionally, regulators have multiple tools in place to expedite the approval of drugs for serious or life-threatening conditions and encourage drug sponsors to take advantage of as many as appropriate. The SPINRAZA marketing application received priority review designation by the FDA and was approved in the U.S. in only three months after submission. For these reasons, the SPINRAZA pathway to marketing approval is an excellent example for the development of gene therapies for the treatment of rare and severe diseases.


Xu,L, et al., “Development of gene therapies – lessons from nusinersen.” Gene Therapy. Accepted article preview 24 July 2017; doi: 10.1038/gt.2017.64