A U.S. pricing watchdog says Eisai Alzheimer’s drug Leqembi (lecanemab) is worth, at minimum, 19% less than its asking price. The report came amid a renewed push for Medicare to expand coverage for Leqembi and similar drugs.
The Institute for Clinical and Economic Review (ICER) estimated Leqembi’s cost-effectiveness “threshold” at between $8,900 and $21,500 per year, according to a report based on currently available evidence. That scale, at the higher end, reflects a 19% discount to the drug’s current list price of $26,500, and 66% off the wholesale acquisition cost at its lower end.
As to why Leqembi’s current list price doesn’t line up with its value, ICER pointed out that the drug shows promise in slowing the disease’s cognitive impairment, but it carries risks of brain swelling and bleeding.
“Currently available evidence is rated as promising but inconclusive to determine whether lecanemab provides a net health benefit over supportive care,” the group explained, adding that there are “uncertainties as to whether the average benefits of lecanemab exceed its risk” in patients with early Alzheimer’s disease.
Nevertheless, the pricey new antibody, which received a green light from the Food and Drug Administration through accelerated approval in January, could see full FDA approval this summer, thanks to securing an expedited “priority review.” Japanese pharma company Eisai and co-developer Biogen said Monday that the regulator set a decision date of July 6 and will convene an advisory committee meeting, although it hasn’t announced when.
Eisai forecasts 100,000 people will be diagnosed with early Alzheimer’s, or mild cognitive impairment (MCI), and become eligible for Leqembi by 2026. The Alzheimer’s Association says more than 2,000 people aged 65 and older transition from the mild form of dementia to moderate disease per day, rendering them ineligible for Leqembi. Typically, early Alzheimer’s affects people 65 and older, leading to cognitive impairment and other issues.
A traditional approval would expand access to the therapy under Medicare. Until then, however, the Centers for Medicare and Medicare Services said it will stand firm on its restrictive coverage policy, published in April 2022, which limits coverage for Alzheimer’s drugs like Leqembi that use antibody treatments to target the plaque that causes the disease.
Under Eisai’s current accelerated approval status, Medicare only reimburses the costs of people in clinical trials approved by the FDA or National Institutes of Health. But because the drugmaker completed a Phase III trial and is not conducting another, Leqembi is out of reach for most.
Eisai, which is leading Leqembi’s U.S. launch, recently recorded the drug’s initial sales and first prescription and patient infusion. Those were for patients who met the criteria for receiving free drugs under Eisai’s prescription assistance program, or those paying cash.
Even if the FDA confers full approval under the priority review process, there’s a chance that Medicare could still restrict coverage to patients enrolled in research approved by CMS, which administers the federal health insurance program. But Eisai is hoping the agency agrees to broader coverage, without restrictions.
In a letter to Health Secretary Xavier Becerra and CMS Administrator Chiquita Brooks-LaSure last month, more than 70 members of Congress agreed, calling for an easing of the coverage restrictions on Leqembi and Alzheimer’s drugs like it.
“Patients, families and caregivers living in rural and underserved areas should have the same opportunity for access to treatment,” the lawmakers wrote. “It is an enormous physical and financial burden for Medicare beneficiaries to spend countless hours traveling to limited research institutions that host the trials.”
The Alzheimer’s Association, in a December letter to CMS, also called for full and unrestricted coverage of Leqembi, calling the agency’s decision to prospectively apply its coverage restrictions to all future FDA-approved drugs within a class “unprecedented.” The group later said it was “appalled” that CMS decided not to amend its earlier decision.
That policy can be traced back to the controversy around Aduhelm, a similar Alzheimer’s antibody treatment developed by Eisai and Biogen. The drug won FDA accelerated approval in 2021 amid disagreement from the agency’s independent advisors that the drug’s data demonstrated a slowing of disease progression. A congressional probe late last year concluded that the Aduhelm approval was rife with improprieties.
In April 2022, CMS published its final decision memo, restricting coverage of all such products, pending more data proving they benefit patients. In January the agency said it would widen coverage if Eisai provides evidence that answers its queries with respect to Leqembi’s ability to slow cognitive decline and the potential risk of side effects.
The American Academy of Neurology (AAN), in a letter to Medicare last month, said there is consensus among its members that the Phase 3 Leqembi trial was well-designed and its findings were clinically and statistically significant.
That trial, known as CLARITY AD, showed that at 18 months, cognitive decline was 27% slower in the lecanemab-treated group versus those who didn’t receive the drug, representing an average half-point difference on an outcome measure known as the CDR-SB. But among those participants, 21.5% experienced brain swelling and bleeding – a group of side effects known as amyloid related imaging abnormalities (ARIA).
Although long-term ARIA data is needed, the AAN said the absence of longitudinal data is insufficient reason for the agency to restrict access to the drug, considering the dire patient need. AAN’s president called on Medicare to reconsider its coverage limitations, so that broader access is in place should the drug win full approval.
ICER acknowledged that the possibility of a “net harm” from ARIA should be weighed against Leqembi’s net health benefits. “We remain uncertain that amyloid removal is an appropriate surrogate outcome for clinical benefit and instead look to the clinical outcomes found in randomized trials,” the group wrote.
“However, there is disagreement among experts about the clinical meaningfulness of the magnitude of change in CDR-SB in the lecanemab trial,” the watchdog pointed out. “We also remain concerned that real-world ARIA occurrences and consequences may be more severe if, as expected, monitoring MRIs are not as frequent as in the clinical trial, the patient population treated differs from the trial population, and clinicians are less expert than those who participated in the randomized trial.”
Eli Lilly’s experimental amyloid-removal antibody donanemab, which received a complete response letter from the FDA in January, was not included in ICER’s report. The agency requested Lilly provide more data, which the drugmaker says will be included in a late-stage version of its clinical trial set to read out later this year.
