Janet Woodcock, acting commissioner of the FDA, published a letter Friday asking the federal government’s top inspector to investigate if FDA staff worked inappropriately with biotech company Biogen to approve the new drug.
“To the extent these concerns could undermine the public’s confidence in FDA’s decision, I believe that it is critical that the events at issue be reviewed by an independent body such as the Office of the Inspector General, in order to determine whether any interactions that occurred between Biogen and FDA review staff were inconsistent with FDA policies and procedures,” she wrote in the open letter.
The drug in question, Aduhelm, was approved by the agency last month and has caused an uproar in the scientific community. Three of the agency’s scientific advisors resigned following the decision.
The interactions pre-dated Woodcock, who became interim commissioner in January when the Biden Administration took office. She has been with the FDA for more than two decades and is one of the top contenders to permanently take the role, according to biotech analysts.
After the FDA approved Aduhelm, Biogen set its price at about $56,000 a year. Analysts estimate the US Medicare program could pay anywhere from $6 billion to $29 billion per year for Aduhelm, according to a recent New York Times analysis.
Biogen’s stock, which surged when the FDA approved Aduhelm, declined 3.2% to $357.09 a share on Friday afternoon.
There were a few surprises that came with the approval of the drug, Aduhelm. For one, there were no real limitations placed by FDA on who will be eligible for the new drug. And the drug costs roughly $56,000 a year.
The latest test of Eli Lilly’s Alzheimer’s disease drug ended with a mixed bag of results, but experts say there are signs the experimental treatment may curb the disease’s decimation of cognition and memory.
Lilly gave an in-depth look at the performance of its drug, called donanemab, on Saturday at the International Conference on Alzheimer’s and Parkinson’s Diseases. The drug met the trial’s primary goals, reducing a harmful substance that builds up in the brains of patients with Alzheimer’s disease. It also slowed down the rate of cognitive decline by 32%, according to data scheduled to be published Saturday in a medical journal. But it missed the mark on several secondary tests.
Those earlier failures – even within Lilly’s own drug-development pipeline – may have tempered expectations for donanemab. Dr. Mark Mintun, the vice president of the Alzheimer’s disease unit at Lilly, said he couldn’t think of a similar Alzheimer’s disease trial that hit its primary goal.
At this point, any news is good news, Dr. Howard Fillit, executive director of the Alzheimer’s Drug Discovery Foundation, told Insider.
“We’ve basically had a 100% failure rate on drug approvals since 2003. The thing that we’re going for is incremental benefits,” he said.
The donanemab data may give hope to the scientific community and other drug companies, but Fillit said the jury is still out on how effective the drug will be for patients themselves.
Donanemab missed the mark on a memory assessment experts were watching
Donanemab was designed to target a plaque that builds up in the brains of Alzheimer’s patients called amyloid beta. The hope is that getting rid of the plaque will reduce the rate of decline of a person’s memory and cognition.
Scans of trial participants’ brains showed that people taking donanemab did see their plaques fade away. That’s not only a boon to Eli Lilly, but other drugmakers that are working on treatments targeting amyloid beta, such as Biogen and Roche.
It wasn’t as clear how much benefit donanemab had on subjects’ ability to recall words, follow instructions and other abilities lost to dementia.
The drug passed the main test of memory and cognition.
But Alzheimer’s experts had their eyes on one datapoint in particular: the scores from a widely accepted dementia assessment known as CDR-SB. The tool is used to measure things like memory and judgement, as well as a person’s ability to do household chores and maintain their personal hygiene. The higher the score, the more skills have been lost to dementia like Alzheimer’s.
Eli Lilly’s drug didn’t meet expectations there.
The company reported that trial participants taking donanemab had a 0.36 point score difference compared to the participants that received a placebo treatment.
For comparison, Dr. Lon Schneider, director of the California Alzheimer’s Disease Center at University of Southern California, had hoped to see at least a one-point difference, according to the Wall Street research firm Mizuho.
Mintun, the Eli Lilly executive, said he hadn’t expected that donanemab would pass all five dementia tests, calling it statistically impossible. But giving patients more time to hold onto memories is meaningful for them, he said.
The clinical trial took a ‘Goldilocks approach,’ and more testing is needed
The donanemab trial assessed a small and very specific group of patients. The trial was limited to participants with amyloid plaques, as well as another protein linked to Alzheimer’s called tau. Fillit called it a Goldilocks approach – in the end, Lilly ended up with participants whose Alzheimer’s disease wasn’t too early or too advanced.
Fillit and Alzheimer’s disease researcher Rudy Tanzi said that Lilly will need to run another clinical trial, preferably a much larger late-stage test with participants from multiple countries, if it wants to bring the treatment to the US Food and Drug Administration for approval. In particular, the company would need to show the drug works, as measured by the CDR-SB score, Tanzi said.
Eli Lilly’s current plan is to run at least one more mid-stage trial. The format of that trial had already been set, but Mintun said the drug giant is discussing possible changes with the FDA, including potentially removing a significant CDR-SB change as the main goal.
Changing that CDR-SB requirement, particularly given that the original Phase 2 trial failed on that regard, would make investors skeptical of the drug, according to a note from Morgan Stanley analysts before the full results were announced.
Shares of Cassava Sciences jumped as much as 16% on Monday on news that the biotech company successfully completed an end-of-phase 2 meeting with the US Food and Drug Administration for Simufilam, its leading drug candidate for the treatment of Alzheimer’s disease. The meeting paved the way for a pivotal phase-three study in the second half of this year.
The Austin, Texas-based company surged toward an almost 10-year high, nearing a share price last seen in June 2011.
“For over 10 years we’ve been doing basic research and early drug development with simufilam,” Remi Barbier, President and CEO of the company said in a statement. “We believe the underlying science is solid, the drug appears safe and the clinical roadmap makes sense. We’ve crossed the Rubicon.
Simufilam is a novel drug that targets “both neuroinflammation and neurodegeneration,” the statement said.