Biogen's Tau Antibody for Progressive Supranuclear Palsy Fails Trial

While all eyes have been on Biogen’s apparent rebirth with the release of its aducanumab data for Alzheimer’s disease, the company had a big trial failure and made a decision to end the program this week.

The company announced topline data from the Phase II PASSPORT trial of gosuranemab for progressive supranuclear palsy (PSP). PSP, also called Steele-Richardson-Olszewski syndrome, is a rare brain disorder that causes problems with walking, balance and eye movements. It is caused by deterioration of brain cells that control body movement and thinking. It is progressive and can lead to life-threatening complications.

The PASSPORT trial did not meet its primary endpoint on the PSP rating scale (PSPRS) at week 52. It also did not show efficacy on key clinical secondary endpoints.

The company indicated it is shutting down its gosuranemab program for PSP and other primary tauopathies.

Gosuranemab is a humanized monoclonal antibody that targets N-terminal tau. Biogen licensed the drug from Bristol-Myers Squibb.

“We are disappointed with the efficacy results of the Phase II PASSPORT study,” said Alfred Sandrock, executive vice president, R&D and chief medical officer at Biogen. “We remain unwavering in our commitment to advancing therapies that have the potential to address the significant unmet medical needs of people with neurodegenerative diseases who are faced with limited to no treatment options.”

The company plans to continue its ongoing Phase II TANGO trial of gosuranemab for mild cognitive impairment related to Alzheimer’s disease or mild AD.

PSP is a tough nut to crack. In July, AbbVie ended its clinical trial of its antibody against tau in PSP after it failed to show clinical benefit. The study was scheduled to wrap in 2020, but an interim data analysis showed no likely benefit.

Of the Biogen trial, analysts for Jefferies wrote in a note to clients that, the failure was a “pipeline setback, but unlikely a surprise to the market… Indeed, combined with what we knew from AbbVie earlier in July, which is their Phase II of a nearly-identical tau antibody that binds the N-terminus of tau, also failed at an interim futility (stopped early due to no efficacy) makes it pretty clear the tau hypothesis is tricky as PSP is one of the most highly prevalent ‘tauopathy’ diseases due to significantly high over-expression of tau and the aggressive nature of the disease.”

Now, more than ever, investors will look to the company’s aducanumab … again.

In March, Biogen and its collaboration partner, Tokyo-based Eisai, announced they were discontinuing the global Phase III trials, ENGAGE and EMERGE, of aducanumab in patients with mild cognitive impairment from Alzheimer’s, as well as the EVOLVE Phase II trial and the long-term extension PRIME Phase Ib trial. An independent data monitoring committee indicated the trials were unlikely to hit their primary endpoints in a futility analysis.

But in late October, the companies announced that after discussions with the U.S. Food and Drug Administration (FDA), and further analysis of the data, they were going to pursue regulatory approval for the drug. The Phase III EMERGE trial met its primary endpoint, showing a significant decrease in clinical decline. The company believes that data from a subset of patients that were given a high enough dose of the drug had significant benefits on measures of cognition and function, including memory, orientation, and language, as well as benefits on activities of daily living.

The company gave a full presentation of data on December 5, which was met with initial enthusiasm, which faded the more researchers and analysts thought about it. The data was complex and mixed—one of the trials failed, one seemed successful, at least in a subset of patients exposed to a high dose of aducanumab. There were concerning safety signals, particular amyloid-related imaging abnormalities, particularly ARIA-E, which refers to cerebral edema. However, the market for Alzheimer’s is so thin and the need so high, there’s still significant hope that the FDA will approve the drug even with marginal benefit.