Accelerated Approval: Gene Therapy Confirmatory Trial Timelines Can Stretch
Executive Summary
Pink Sheet infographic looks at the nascent space of gene therapy accelerated approvals, where confirmatory trial timelines can run many years beyond approval due to disease rarity and a focus on durability of response.
The US Food and Drug Administration has granted accelerated approval to four gene therapies to date, including three anti-cancer CAR-T products and bluebird bio’s cerebral adrenoleukodystrophy treatment Skysona (elivaldogene autotemcel).
New confirmatory trials were required for all of them. In the case of Skysona, the last study report is not due until December 2038, more than 16 years after approval.
This Pink Sheet infographic takes a deep dive into the confirmatory trials and timelines for the four gene therapies under accelerated approval.
A Stretch Over Time: Gene Therapy Accelerated Approval Confirmatory Trials
Click on the bars to view timelines for accelerated approval postmarketing requirements for four gene therapies.
Gene Therapy Confirmatory Trials In Focus
See more details on each postmarketing requirement, categorized by product.
| Product | |||
| SKYSONA (elivaldogene autotemcel) | KYMRIAH (tisagenlecleucel) | YESCARTA (axicabtagene ciloleucel) | TECARTUS (brexucabtagene autoleucel) |
| Company | |||
| bluebird bio | Novartis | Kite (Gilead) | Kite (Gilead) |
| Product Type | |||
| Genetically modified autologous CD34+ hematopoietic stem cells | CD19-directed CAR-T cell immunotherapy | CD19-directed CAR-T cell immunotherapy | CD19-directed CAR-T cell immunotherapy |
| Application Type | |||
| Original | Supplement | Supplement | Original |
| Approval Date | |||
| September 2022 | May 2022 | March 2021 | July 2020 |
| Indication | |||
| To slow the progression of neurologic dysfunction in boys 4-17 years of age with early, active cerebral adrenoleukodystrophy (CALD) | Third-line relapsed/refractory follicular lymphoma | Third-line relapsed/refractory follicular lymphoma | Relapsed/refractory mantle cell lymphoma |
| PMR1 | |||
| Follow all subjects who received elivaldogene autotemcel in Studies ALD-102 and ALD-104 to assess event-free survival (i.e., alive without Major Functional Disability (MFD) or need for hematopoietic stem cell transplant (HSCT)) for a minimum of 10 years following administration of elivaldogene autotemcel. Milestone Dates:
Status: Pending - Protocol submitted |
Conduct a randomized Phase III trial in adult patients with r/r follicular lymphoma. Patients will be randomized to tisagenlecleucel or an investigator’s choice of regimens consistent with the standard of care. The primary endpoint will be progression-free survival with secondary endpoints that include overall survival and objective response rate. Milestone Dates:
Status: Pending - Protocol submitted |
A randomized Phase III trial of axicabtagene ciloleucel in patients with r/r follicular lymphoma. Patients will be randomized to axicabtagene ciloleucel or to an investigator’s choice of regimens consistent with the standard of care. The primary endpoint will be progression-free survival, with secondary endpoints that include objective response rate and overall survival. Milestone Dates:
Status: Ongoing - Actual study start - September 2022 Est. primary completion date - July 2029 |
Complete additional follow-up of all 68 subjects treated with brexucabtagene autoleucel in ZUMA-2 Cohort 1 to a minimum of 18 months from the time of first response. Data will continue to be collected according to the ZUMA-2 protocol’s established schedule of assessments. Milestone Dates:
Status: Fulfilled |
| PMR2 | |||
| Investigate event-free survival for at least five years post-treatment in 24 boys with more advanced early active CALD (based on baseline Loes scores and Neurologic Function Score (NFS)) who will be newly treated with elivaldogene autotemcel. Milestone Dates:
Status: Pending - Protocol submitted |
Conduct a study of brexucabtagene autoleucel treatment of subjects with r/r mantle cell lymphoma who have not been exposed to a Bruton tyrosine kinase (BTK) inhibitor. A cohort of subjects naïve to BTK inhibitor therapy will be added to the ongoing ZUMA-2 study to fulfill this requirement. 86 subjects will be enrolled. The primary efficacy endpoint will be objective response rate with a supportive efficacy endpoint of duration of response based on a minimum follow-up of 18 months after first objective disease response.
Milestone Dates:
Status: Ongoing Actual study start: April 2021 |