Case studies

To conclude this section, we will highlight the currently FDA-approved (including accelerated approvals) AAV gene therapies. There are five that fall in this category as of this version of the playbook, which are shown in figure below.

From the five approved therapies, Zolgensma was awarded all the special designation programs (except for RMAT). We will highlight some of the important milestones for Zolgensma in the next section.

FDA Approved AAV Gene Therapies (in vivo gene replacement)

KEBILIDI

Approved Indication: KELIBIDI is an adeno-associated virus vector-based gene therapy indicated for the treatment of adult and pediatric patients with aromatic L-amino acid decarboxylase (AADC) deficiency. Kebilidi was approved using the Accelerated Approval pathway and also received Priority Review and Orphan Drug designation.

• Link to FDA approved package insert/labeling and other publicly available regulatory documents

LUXTURNA

Approved Indication: LUXTURNA is an adeno-associated virus vector-based gene therapy indicated for the treatment of patients with confirmed biallelic RPE65 mutation- associated retinal dystrophy. Patients must have viable retinal cells as determined by the treating physician(s).

•  Link to FDA approved package insert/labeling and other publicly available regulatory documents

HEMGENIX

Approved Indication: HEMGENIX is an adeno-associated virus vector-based gene therapy indicated for the treatment of adults with Hemophilia B (congenital Factor IX deficiency) who currently use Factor IX prophylaxis therapy, have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes.

• Link to FDA approved package insert/labeling and other publicly available regulatory documents

ELEVIDYS

Approved Indication: ELEVIDYS is an adeno-associated virus vector-based gene therapy indicated for the treatment of ambulatory pediatric patients aged 4 through 5 years with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene. This indication is approved under accelerated approval based on expression of ELEVIDYS microdystrophin in skeletal muscle observed in patients treated with ELEVIDYS. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

• Link to FDA approved package insert/labeling and other publicly available regulatory documents

ROCTAVIAN

Approved Indication: ROCTAVIAN is an adeno-associated virus vector-based gene therapy indicated for the treatment of adults with severe hemophilia A (congenital factor VIII deficiency with factor VIII activity < 1 IU/dL) without pre-existing antibodies to adeno-associated virus serotype 5 detected by an FDA-approved test.

• Link to FDA approved package insert/labeling and other publicly available regulatory documents

ZOLGENSMA

Approved Indication: ZOLGENSMA is an 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.

• Link to FDA approved package insert/labeling and other publicly available regulatory documents

You may refer to the FDA’s Expedited Approval Mechanisms for New Drug Products as an additional resource on this topic.

Now that you have the overview of all special programs, including paths taken by previously approved AAV gene therapies, you’re more prepared for your IND submission journey – in the next section.