FDA Viral and Gene Therapy Approvals
Approvals

FDA Viral and Gene Therapy Approvals

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One virus therapy and two gene therapies have been approved by FDA in the last 10 years. The FDA website contains public information on the CMC review discussions, information requests, manufacturing inspections, and the advisory committee discussions. 

Understanding the regulatory history for these successful applications is often an underutilized tool in planning for new product applications.  The summary basis of approvals are a good place to get started, followed by cross referencing the of NCT (National Clinical Trial) numbers on the clinicaltrials.gov website, and then a deep dive into the CMC information requests and advisory committee minutes.

Note:  All text below is extracted from the FDA website.

Imlygic (talimogene laherparepvec) is an attenuated herpes simplex virus type 1 (HSV-1), engineered to express human granulocyte macrophage colony stimulating factor (GM-CSF) to enhance the response to tumor antigens released during virus replication. Imlygic is indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery.

IND (2005) to BLA approval (2015):  10 years

  • FDA had a combined CTGTAC and ODAC meeting to discuss this BLA submission on April 29, 2015
  • Clinical Trials:  Multiple clinical trials conducted with over 500 subjects in the US, Canada, South Africa and UK

Luxturna (voretigene neparvovec-rzyl) LUXTURNA is a recombinant adeno-associated virus serotype 2 (AAV2) vector expressing the gene for human retinal pigment epithelium 65 kDa protein (hRPE65), for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy.

IND (2007) to BLA approval (2018):  11 years

  • A meeting of the Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) was held on October 12, 2017 to provide feedback to FDA regarding clinical efficacy and safety, and an overall benefit-risk assessment of LUXTURNA.
  • The Luxturna approval is supported by clinical data from a Phase 1 study and a Phase 3 study.  The Phase 3 study provides the primary evidence of effectiveness. Both the Phase 1 and Phase 3 studies contribute to the safety database. Forty-three subject were enrolled.

Zolgensma (onasemnogene abeparvovec-xioi) is a recombinant adeno-associated virus (AAV) vector-based gene therapy indicated for the treatment of pediatric patients less than 2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene.

IND (2013) to BLA approval (2019):  6 years

  • No advisory committee meeting was held because initial review of information submitted in the BLA did not raise concerns or controversial issues that would have benefited from an advisory committee discussion.
  • The safety population included a total of 44 patients with SMA who received intravenous infusion of ZOLGENSMA in four clinical trials conducted in the United States, including the completed Phase 1 trial, two ongoing trials, and an ongoing observational long-term follow-up study. Forty-one patients received ZOLGENSMA at or above the dose of 1.1 × 1014 vg/kg, and 3 patients received a lower dose. The patient population ranged in age from approximately 2 weeks to 8 months at the time of infusion.