On January 11, the US Facilities for Medicare and Medicaid Providers (CMS) launched a draft model of its extremely anticipated reimbursement resolution concerning Biogen and Eisai’s Aduhelm (aducanumab) and different future anti-amyloid monoclonal antibody (mAb) merchandise in Alzheimer’s illness (AD): CMS proposed the reimbursement of Meals and Drug Administration (FDA)-approved anti-amyloid mAb merchandise below a protection with proof improvement (CED) coverage. The CED requirement will restrict Medicare reimbursement of Aduhelm to AD sufferers collaborating in randomised managed trials (RCTs). Concerning enrollment in these RCTs, CMS acknowledged that it will cowl the price of one beta-amyloid positron emission tomography scan per affected person, however would restrict research participation to sufferers with gentle cognitive impairment (MCI) attributable to AD or gentle AD dementia, which is in step with the FDA label for Aduhelm. Though this preliminary protection resolution indicators some hope for the anti-amyloid mAb class in the long run, it is going to considerably delay and restrict affected person entry to those merchandise within the close to time period, with Aduhelm seemingly bearing the brunt of those troubles.
Aduhelm was authorized in June 2021 by means of the FDA’s accelerated approval pathway, based mostly on the surrogate endpoint of amyloid clearance. Though its approval was a serious milestone for the AD neighborhood, the drug’s launch has been marred by controversy surrounding the FDA’s resolution, which conflicted with its advisory board’s opinion, and ongoing disputes concerning the drug’s risk-benefit profile. Because of this tumultuous market entry, as of Q3 2021, Aduhelm had solely introduced in $300,000 in income. Key opinion leaders interviewed by GlobalData in December 2021 projected that till a trial can show the medical advantage of amyloid discount in AD, there’ll stay a big contingency of physicians, payers and sufferers who is not going to really feel comfy with Aduhelm’s risk-benefit profile and price. This want for extra information is precisely what spurred CMS’s resolution for a CED requirement. On the finish of 2021, Biogen and Eisai offered an replace on their deliberate Part IV confirmatory trial of Aduhelm, required by the FDA as a part of the drug’s accelerated approval. With affected person screening seemingly starting in Could 2022, Biogen and Eisai anticipate a major completion date roughly 4 years after research begin. A 4 or extra yr wait earlier than gaining extra widespread Medicare protection may very well be disastrous for the product.
Moreover, Aduhelm’s prospects could also be improved or worsened by the successes and failures of the three anti-amyloid mAb merchandise in pipeline improvement: Eisai and Biogen’s lecanemab, Roche/Genentech’s gantenerumab, and Eli Lilly’s donanemab. All three merchandise are at present in Part III trials, with anticipated readouts in H2 2022 and H1 2023, which is able to assist to extra definitively verify or deny the medical relevance of amyloid discount within the therapy of AD. The primary outcomes will seemingly come from Roche/Genentech’s GRADUATE 1 (NCT03444870) research of gantenerumab, with a major completion date of Could 31, 2022. Additional information from Roche/Genentech’s GRADUATE 2 (NCT03443973) research is anticipated in the direction of the top of 2022. Round this time, information can also be anticipated from the CLARITY AD (NCT03887455) research of lecanemab. Lastly, Eli Lilly’s TRAILBLAZER-ALZ 2 (NCT04437511) research of donanemab is anticipated to succeed in its major completion date in H1 2023.
Though optimistic competitor information supporting the medical advantage of amyloid clearance might give Aduhelm gross sales a small enhance, by the point this information is launched, Aduhelm will not be the one anti-amyloid remedy in the marketplace. Eisai and Biogen together with Eli Lilly are anticipated to pursue accelerated approval for lecanemab and donanemab, respectively, based mostly on the surrogate endpoint of amyloid discount, with each coming into the AD market in Q3 2022. One other complicating issue is the uncertainty concerning how shortly optimistic medical information from different anti-amyloid mAb merchandise might persuade CMS to finish the CED requirement on this class of merchandise. Within the draft steering, CMS proposed that investigators could lengthen RCTs to potential longitudinal research as soon as the RCT portion is accomplished and the drug has demonstrated a clinically significant profit in cognition and performance. This means CMS could need to see additional long-term information on anti-amyloid mAb efficacy and security earlier than increasing entry, which might spell hassle for all anti-amyloid mAbs, not simply Aduhelm.
Regardless of Aduhelm’s first-to-market benefit, the months of controversy following the drug’s approval have been a serious setback. Though CMS’s steering can nonetheless doubtlessly change, with a closing resolution anticipated in April, this preliminary resolution is one more blow for the drug. GlobalData expects that continued delays in Aduhelm’s roll-out will seemingly permit rivals to enter the AD market earlier than the drug can firmly set its roots. Based mostly on Aduhelm’s delayed uptake trajectory, in addition to its lately slashed worth (practically 50% of the unique), GlobalData estimates that by 2028, the product will attain gross sales of $906.1m, solely 1 / 4 of the gross sales GlobalData had forecasted for the drug beforehand.