About six months after granting accelerated approval to Leqembi (lecanemab) for mild cognitive impairment caused by Alzheimer’s disease (AD), the U.S. FDA gave its full blessing to the amyloid-beta binder from Biogen Inc. and Eisai Co. Ltd.

The full approval was largely expected, although Leqembi has been dogged by some doubt along its trajectory. A recent survey by the social-network platform Sermo of more than 650 physicians found that 81% supported the move, as 90% felt that this drug gives renewed hope to patients with AD, though 85% of those surveyed also expressed concern about the deaths linked to the drug. What does it mean for Leqembi’s commercial ramp? The jury’s still out. Mizuho analyst Salim Syed noted that his firm hosted a conference call with key opinion leaders (KOLs), and they view a surge in sales possible but not certain. The Centers for Medicare & Medicaid Services (CMS) registry shouldn’t be a problem, in the KOLs’ view, and “blood-based diagnostics weren't exactly cited on the call as a requisite to a commercial inflection, if one were to occur,” Syed said in a June 23 report. CMS recently issued a fact sheet with detailed plans for coverage of new AD therapies, including Leqembi, a move that eased some frets about the drug’s coverage odds.

Piper Sandler analyst Christopher Raymond said in a report the same day as Syed’s that “the information required for this registry is already routinely captured and should not be excessively onerous.” His firm conducted a survey, too, and found that “Leqembi uptake is poised to accelerate meaningfully – potentially providing upside to expectations earlier than investors may anticipate.” Raymond provided details of the survey in an April 17 report. “While we don’t anticipate this launch lighting the world on fire in the near term,” he said, the findings “indicate robust uptake after full approval and subsequent CMS reimbursement. Coupling that with meaningful expense leverage and a fresh management approach, we like the intermediate- to longer-term set up on this name,” he said. The research firm Spherix tapped 73 neurologists/AD specialists in March. “While share today is minimal (0.7% of patients), docs project this share to almost quadruple within six months,” he said, with peak projected at almost 24%. “Pen to paper, these projections would infer an annual U.S. run rate north of $500 million” within that time period, Raymond added. “For perspective, U.S. consensus is just $49 million this year and $2.9 billion in 2027.”

Meanwhile, pricing of Leqembi has made some waves. When Leqembi gained its accelerated nod, Eisai said in a statement that, “while we estimate the per-patient-per-year value of Leqembi treatment to the U.S. society to be $37,600, Eisai decided to price [the drug] below quantified societal value at the wholesale acquisition cost (WAC) of $26,500 per year (estimated annual price based on 10 mg/kg I.V. biweekly for the average U.S. patient weight of 75 kg, based on study 201 and Clarity AD), aiming to promote broader patient access, reduce overall financial burden, and support health system sustainability. As such, the WAC for the 200-mg vial is $254.81 and the WAC for the 500-mg vial is $637.02,” the company said, though actual annualized pricing may vary by patient. The Institute for Clinical and Economic Review concluded in its report in December of last year that Leqembi would be cost-effective if priced between $8,500 and $20,600 per year.

Sen. Bernie Sanders (I-Vt.), chairperson of the Senate Health, Education, Labor, and Pensions Committee, in early June sent a letter to U.S. Department of Health and Human Services Secretary Xavier Becerra urging the Biden administration to protect patients and act to substantially reduce the price of Leqembi. “Alzheimer’s is a horrible disease,” Sanders wrote. “We must do everything possible to find a cure for the millions of people who suffer from it. But we cannot allow pharmaceutical companies to bankrupt Medicare and our federal government in the process. If we are serious about reducing the national debt, we must substantially lower the price that Medicare pays for prescription drugs [such as] Leqembi.” Also that month, Sanders called for U.S. President Joe Biden to reinstate, and strengthen, a “reasonable pricing clause” in all future research agreements involving government agencies, especially those funding drug R&D. To back his argument, Sanders released a report, prepared by the HELP Democratic majority staff, detailing two case studies that involve Hemgenix (etranacogene dezaparvovec) from CSL Behring LLC and Yescarta (axicabtagene ciloleucel) from Kite, a unit of Gilead Sciences Inc.

Under the Inflation Reduction Act (IRA), Leqembi wouldn’t be subject to price negotiations for 11 years (from the date of first approval, i.e., its accelerated approval). Even then, it would have to be one of the drugs with the biggest Medicare spend at the time to be chosen for negotiations.

While the IRA exempts biologics from negotiations if they have actively marketed biosimilars, the Biologics Price Competition and Innovation Act grants biologics 12 years of market exclusivity. Thus, a big-spend biologic would be forced into giving up some of its exclusivity, as well as patent protection, in order to avoid negotiations. This might be done via licensing deals, such as the ones Abbvie struck with Humira biosimilar sponsors. (The law also allows up to two years’ delay from negotiations if a biosimilar will be launching within that time. The request has to be made by the biosimilar sponsor.) Also exempted from negotiations are “low-spend” drugs with less than $200 million per year in combined Medicare parts B and D spending.

The need for new AD drugs persists. A newsmaker in the space lately is Austin, Texas-based Cassava Sciences Inc., which July 5 offered top-line results from its cognition maintenance study, a small proof-of-concept study designed to show the effects of oral simufilam vs. placebo when tested in a randomized withdrawal trial design. The experiment signed up 157 patients with mild to moderate AD. In the double-blind, placebo-controlled, randomized efforts, all patients first were given open-label simufilam 100 mg for 12 months. They were then randomized 1:1 to receive either simufilam 100 mg or placebo for six months. Sixteen U.S. clinical sites participated. The study had one pre-specified cognitive endpoint: mean change in ADAS-Cog11 scores over six months with the drug compared to placebo. The drug, meant to restore the normal shape and function of altered filamin A protein in the brain, turned up a slowing of cognitive decline by 38% vs. sham. The placebo arm declined 1.5 points on an AD measuring tool, and this arm declined at all timepoints examined. The simufilam arm dropped 0.9 points to make the 38% difference (95% CI, – 2.1 to 1.0; not significant for sample sizes). Cassava is evaluating simufilam tablets for AD dementia in two phase III trials.

Discoveries continue to emerge from the cognitive impairment/AD space. At the American Society of Clinical Oncology meeting in Chicago recently, data from a phase III study called Remember with the AD therapy donepezil found that the acetylcholinesterase inhibitor did not significantly improve cancer-related shortfalls in cognition among breast cancer survivors. Data from 276 women were analyzed.