Timrepigene Emparvovec Fails to Demonstrate Efficacy in Choroideremia


Detailed data from the phase 3 trial, including safety findings, which were in line with previous studies, will be presented at a future scientific meeting.

The phase 3 STAR study of timrepigene emparvovec (NCT03496012; BIIB111/AAV2-REP1), an investigational gene therapy for the potential treatment of choroideremia, did not meet its primary or secondary efficacy endpoints, according to an announcement from Biogen.1 

Choroideremia is a rare, degenerative, X-linked inherited retinal disorder that leads to blindness.2 It is caused by loss of function mutations in the choroideremia gene resulting in decreased REP-1 expression which leads to degeneration of the retinal pigment epithelium, photoreceptors, and choroid. Timrepigene emparvovec is an investigational recombinant AAV2 vector that aims to address the underlying genetic cause of choroideremia by delivering a functional version of the human choroideremia gene into the retinal pigment epithelium and photoreceptor cells, delivered via a single subretinal injection.

The primary end point of the STAR study was proportion of participants with an at least 15 letter improvement from baseline in best corrected visual acuity (BCVA) at month 12 as measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart. The multicenter, 3-arm, parallel-controlled group trial enrolled 169 adult males with genetically confirmed diagnosis of choroideremia who were randomly assigned to high- or low-dose treatment, or placebo. The intervention failed to meet this end point and also failed to demonstrate efficacy on key secondary end points. 

Safety results were consistent with previous studies. Detailed results will be presented at a future scientific meeting, along with next steps for the clinical development program. 

READ MORE: Optogenetic Gene Therapy Restores Vision in 11 Retinitis Pigmentosa Patients

Biogen’s acquisition of Nightstar Therapeutics in June 2019 added the investigational treatment to its portfolio. The FDA previously granted regenerative medicine advanced therapy designation to timrepigene emparvovec.2

The STAR study was originally initiated based on proof-of-concept data from phase 1/2 studies, which showed that at month 24, over 90% of patients treated with timrepigene emparvovec maintained visual acuity unlike expected BCVA loss in natural history of choroideremia. Twenty-one percent of treated patients with moderate to severe visual acuity loss experienced a gain in visual acuity of at least 15 ETDRS letters from baseline compared to 1% of untreated patients in a natural history study.

“Timrepigene emparvovec could be a transformative gene therapy for individuals living with choroideremia who would otherwise face inevitable blindness,” Alfred Sandrock, Jr., MD, PhD, executive vice president, Research and Development, and chief medical officer at Biogen, said in a previous statement about the initially promising data.2

1. Biogen announces topline results from phase 3 gene therapy study in choroideremia. News release. Biogen. June 14, 2021. https://finance.yahoo.com/news/biogen-announces-topline-results-phase-200600338.html
2. Biogen announces enrollment completion of global phase 3 gene therapy study for an inherited retinal disorder. News release. Biogen. November 21, 2019. https://investors.biogen.com/news-releases/news-release-details/biogen-announces-enrollment-completion-global-phase-3-gene
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