Psy-Q: How can clinicians address questions from patients and families about the newly approved and controversial Alzheimer’s drug aducanumab? Reshma Ramachandran MD, MPP, answers.

Reshma Ramachandran, MD

Reshma Ramachandran, MD

Answer: Managing patient and family expectations of a new Alzheimer’s disease (AD) drug can be difficult when so many in the scientific community disagree with the FDA’s decision to make it available, says Reshma Ramachandran MD, MPP, a physician-fellow at the National Clinician Scholars Program at the Yale School of Medicine and co-author of an opinion piece in CNN that details why the FDA’s decision sets a “perilous precedent” that puts doctors and patients in a difficult position.

“The way that I’ve been talking to patients and families is to take a step back and say that I think we have the shared goal of really wanting to find an option to help treat this disease, but unfortunately, based on the data that we have available, we just don’t know if this drug is it,” Dr. Ramachandran told Psycom Pro.

When the FDA approved Biogen’s AD drug aducanumab earlier this month, the outcry among medical professionals was swift due to what many say is a lack of data supporting its efficacy and safety. Three of the 11 members of the FDA’s advisory committee, which did not recommend approval, resigned in protest of the agency’s decision.

Patients received news of the approval and information about the drug from patient advocacy groups, and some seen in Dr. Ramachandran’s office just two days after the drug was approved asked when they could get this treatment. “It was interesting to hear them approach it from that lens of not a question of, ‘Is this drug a good option?’ but, ‘When can we get it?’ because they had seen so much positive information,” Dr. Ramachandran says.

The problem, she notes, is that the materials that patients received from groups like the Alzheimer’s Association overstated the benefits but also downplayed the risks of the drug, which gives people a lot of hope about this treatment. She points out that patient groups are not obligated to follow the same rules as a manufacturer when talking about efficacy and safety, and that this was interesting to see from the patients’ perspective.

“I had seen snippets of this, but seeing it from the patients and seeing that they were relying on this information, really as guidance, was very troubling to see that the same rules that would apply to Biogen do not apply to these groups,” she says.

When she spoke to patients asking about aducanumab, Dr. Ramachandran explains how she walked patients through the controversy about the decision, her concerns about the effectiveness, and the safety risks:

  • It was tested in a narrow patient population with Alzheimer’s disease, those with mild cognitive impairment or early Alzheimer’s.
  • After the study had been stopped due to futility, the company and FDA re-analyzed data differently. One study then showed no benefit and the other study showed something that was not clinically significant.
  • The expert advisory committee told the FDA that this was not clinically meaningful and recommended another trial before approval.
  • The FDA recognizes, to an extent, that there wasn’t a clinical benefit, which is why they gave it accelerated approval that requires another trial, within 9 years, that will hopefully show some kind of benefit.
  • In terms of risks, 35% of patients in the trials had brain swelling and almost one-fifth of patients had multiple brain bleeds, and we have no follow-up of what happened to these patients after the trial. There are summary results from the briefing document given to the advisory committee and we expect the full results in July, says Dr. Ramachandran, but that “right now we’re kind of flying in the dark in terms of even understanding the risks of this drug.”

When she reviewed this information with a number of patients and families, she says that they did pause and wanted more information before pursuing the use of the drug. But a few patients with more progressive AD, Dr. Ramachandran says, were a bit torn, “The disease has progressed so much that for them even the risks seemed something that could be overcome because the drug seemed to offer some hope.”

The feeling of not having options to offer patients is particularly difficult in this situation, says Dr. Ramachandran. “That was, I think, the toughest part for me in terms of talking about this drug because we now have something that has the rubber stamp of the FDA, but at the same time, the approval and at least the data that we have available does not look promising at this moment.”

Looking for help with having these difficult conversations with patients, Dr. Ramachandran and her colleagues have called on medical professional societies to provide guidance and scripts that they can use. She hopes to have those resources soon, especially since the first dose of the drug was administered last week. (See also, additional perspectives on the aducanumab approval.)

Ultimately, the FDA’s approval of aducanumab has shaken the trust that the agency is approving drugs that are truly safe and effective, Dr. Ramachandran says. “That safeguard that we have as clinicians in saying that this is an FDA-approved drug so it must come with safety and efficacy standards has really been struck down in some ways. And that’s my big worry—that this is just lowering the bar so much that we’re going to see manufacturers saying, ‘Why not me, too?’ in terms of getting their drugs approved on the same standards.”

Update: On July 8, 2021, the FDA updated the aducanumab label (100 mg/mL solution injection) regarding indications and usage. The update for the drug (branded Aduhelm from Biogen and  Eisai Co.) states: “ADUHELM is indicated for the treatment of Alzheimer’s disease. Treatment with ADUHELM should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. This indication is approved under accelerated approval based on reduction in amyloid beta plaques observed in patients treated with ADUHELM. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s).”

Last Updated: Jul 8, 2021