After Controversial AD Drug Win, Biogen's Retinal Gene Therapy Flops

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Pivoting from conflicting and controversial press over its recently approved Alzheimer’s disease treatment, Biogen has announced yesterday that its gene therapy drug timrepigene emparvovec has failed to show a clinically meaningful benefit for a rare inherited eye disease in a Phase III trial.

The late-stage STAR study enrolled 169 adult males with choroideremia, an inherited retinal disease characterized by progressive vision loss and ultimate blindness. The investigators evaluated the efficacy and safety of a single subretinal injection of the investigational gene therapy timrepigene emparvovec. This drug was designed to deliver a functional human choroideremia gene into photoreceptor cells and the retinal pigment epithelium to address the condition’s underlying genetic causative mechanisms.

In a statement on the STAR findings, Biogen stated the study failed to meet the primary endpoint of the proportion of patients who experienced a ≥15-letter improvement in the best corrected visual acuity (BCVA) at one year in the intervention arm versus the control group. The primary endpoint was assessed using the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart.

Also, Biogen reported that the trial failed to show efficacy regarding the key secondary endpoints. However, the safety findings from the study were generally consistent with previous research trials. 

“We extend our deepest gratitude to all those who contributed to the STAR study, including the participants, investigators, site staff and the broader choroideremia community,” said Katherine Dawson, M.D., Biogen’s Head of the Therapeutics Development Unit. 

“While we are disappointed by the results of the STAR study, we are hopeful that the clinical insights gleaned from this study may help to shape therapeutic innovation for inherited retinal diseases including choroideremia, so that in the future there may be treatment options for the community affected by these debilitating disorders.”

The company noted it would continue to assess the STAR study’s complete data set before confirming its future plans for clinical development of timrepigene emparvovec. 

These topline results from the STAR trial follow a controversial approval of Biogen’s Alzheimer’s drug Aduhelm (aducanumab). As reported by the company on June 7, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the therapy to address the accumulation of amyloid beta plaques in the brain associated with the neurologic disease. 

The approval was based on clinical trial data showing the therapy could reduce these plaques, but these studies did not demonstrate an overall clinically meaningful reduction in cognitive decline. Instead, the plaques serve as a biomarker for cognitive dysfunction in patients with Alzheimer’s disease, and both Biogen and some regulators at the FDA surmise the reduction in these plaques could possibly provide a beneficial effect.

But as reported in opinion pieces in the New York Times and Bloomberg, among other publications, the approval of the dementia drug is based on “spotty evidence,” which serves to threaten the FDA’s reputation. 

As such, three-panel members of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee have resigned from their posts in protest over the Aduhelm approval. 

“My rationale was that the FDA needs to re-evaluate how it solicits and uses the advisory committees … because I didn’t think that the firm recommendations from the committee in this case … were appropriately integrated into the decision-making process,” said one of the resigning members, Aaron Kesselheim, a professor of Medicine at Harvard Medical School, in an interview with Reuters.