Just a handful of days are left until patients, families, investors and Biogen executives will know the next chapter for the company’s controversial Alzheimer’s disease drug candidate aducanumab. But even if the drug scores its coveted FDA nod, a quick rollout is no sure thing, analysts say.
Confusion among physicians, resistance from payers and even the need for frequent follow-ups could slow the launch, pharma watchers said.
The FDA is slated to deliver a decision on aducanumab by June 7. If the agency approves the drug, physicians might still struggle with key questions such as who should get it and for how long. Payers might balk at its price and erect extra hurdles that could significantly limit its reimbursement, analysts warn. And a potential requirement for constant patient screening and monitoring may also stress the healthcare system.
Back in November, a panel of independent FDA advisers voted overwhelmingly against aducanumab, arguing that existing conflicting clinical trial results don’t prove the drug is effective. The resounding snub reflects that some practicing doctors likely aren’t convinced of aducanumab’s efficacy and may be reluctant to prescribe it.
If approved, aducanumab would be the first disease-modifying therapy for Alzheimer’s. The many unknowns behind that first have some physicians concerned, SVB Leerink analyst Marc Goodman said in an investor note ahead of the advisory committee meeting.
Biogen’s been positioning the anti-beta amyloid drug for early-stage symptomatic patients who test positive for beta-amyloid plaques. However, mixed results from the two phase 3 clinical trials have left many wondering whether the drug only works in a yet unidentified subgroup of patients—or at all.
An Alzheimer’s specialist Goodman interviewed at the time said that many of his colleagues are skeptical about aducanumab and would like to see more data from an additional phase 3 trial to confirm its effect.
Aside from that concern, patients in aducanumab’s clinical trials were only treated for 18 months, so questions remain as to how long patients should remain on treatment, as well as how often physicians should monitor for a side effect called amyloid-related imaging abnormalities (ARIA) that involves swelling in the brain. The Alzheimer’s expert Goodman spoke with believes it would be easy to have a symptom-based management program that tests patients when they have a headache, but he would find it more cumbersome to monitor for asymptomatic ARIA.
But reluctance from physicians may be the easiest hurdle to cross for a potential launch.
“Doctors will be under pressure from their patients and their patients’ families to use the drug because there’s really nowhere else to go,” Mizuho analyst Salim Syed said during a recent interview.
Payers could represent a bigger problem for Biogen’s rollout.
The FDA can give its green light, but payers will likely turn to their own experts to evaluate reimbursement dynamics, RBC Capital Markets analyst Brian Abrahams noted in a report in December. “If their own experts mirror AdComm panelists, access could be limited depending on the payer,” he said. It typically takes months after approval for payer committees to review drugs, and early payer feedback suggests that aducanumab would be no different, he added.
“We will be ready to support and prepare our clients to ensure appropriate and affordable access to this therapy if the FDA approves aducanumab,” Express Scripts said in a statement shared with Fierce Pharma. “As with all newly approved medications, the Express Scripts independent Pharmacy & Therapeutics Committee would review the clinical data for aducanumab and share a coverage recommendation in the coming months.”
It’s not unprecedented for insurers to push back at controversial new medicines. After Sarepta Therapeutics’ Duchenne muscular dystrophy drug Exondys 51 won its approval in 2016, some large plans initially rejected access and said the drug hadn’t proven its clinical benefit. Coverage improved after patient advocacy groups brought the restrictions to the public spotlight, but plans continue to deny access even today, Abrahams said.
While that’s just one “anecdotal example,” the Sarepta situation illustrates that payers need “demonstrated clinical rationale” and support from influential doctors to sign off on coverage, he added.
Mizuho’s Syed suggested that payers will “thread the needle” if aducanumab gets its go-ahead.
“I don’t think payers are going to … say 'absolutely not' because at the end of the day it’s an FDA-approved product,” he said in an interview. “But they will make it difficult.”
Payers could base their decision on the total healthcare spending burden associated with aducanumab, and they might also try to identify the patients with the best chances of responding, Syed said.
On the pricing front, the analyst suggested that Biogen should pay attention to recommendations from the Institute for Clinical and Economic Review. The U.S. drug cost watchdog recently said aducanumab’s list price should fall between $2,500 to $8,300 to be considered cost-effective. In reaching the numbers in a draft report, it also pointed to “insufficient” evidence on the drug’s benefits.
In the end, Abrahams believes initial coverage for aducanumab will be “highly fragmented.” The situation may improve as real-world experience accumulates and if, more importantly, organizations such as the American Academy of Neurology include the drug in their guidelines, which he said would be hard for payers to ignore.
Aside from doctor concerns and payer restrictions, patient selection and monitoring could prove to be another stumbling block.
As Biogen’s head of neurodegeneration development, Samantha Budd Haeberlein, explained during the advisory committee discussion, aducanumab’s filing included language that amyloid testing such as a PET scan should be used before starting treatment. But as Biogen CEO Michel Vounatsos noted during an investors conference call in April, neither PET nor an alternative cerebrospinal fluid amyloid testing are currently covered by payers.
Biomarker screening is already popular in cancer treatment, so as Vounatsos put it, “there is a path forward” for reimbursement for amyloid diagnostics. The problem with aducanumab, though, is that it may require regular doctor visits and testing to ensure that patients remain mild to be eligible to stay on the treatment. That tracking of disease development, plus the ARIA monitoring, could further overwhelm the current system.
A 2017 study (PDF) by the Rand Corporation predicts that patients would have to wait an average of 18.6 months for Alzheimer’s treatment in 2020—assuming a disease-modifying therapy reaches the market that year—thanks to limited capacity of dementia specialists, access to imaging testing and to infusion centers. Biogen sponsored the study.
“We know that the availability of specialist and diagnosis capabilities are a bottleneck,” Vounatsos said during the call. About 600 care facilities will be able to treat patients with aducanumab upon a potential approval, Biogen figures.
In all, the expert Goodman interviewed projected a slow sales ramp for aducanumab given the multiple barriers ahead. The specialist thinks it “may take a while to establish the infrastructure and capability for using adu in practice,” Goodman wrote.
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