After the FDA rejected an accelerated approval bid in January, Eli Lilly has returned with topline data proving that donanemab may be an effective alternative to Leqembi (lecanemab) in treating Alzheimer鈥檚 disease.
On May 3, Eli Lilly announced that donanemab slowed Alzheimer鈥檚 progression by 35% in patients compared to placebo. However, as donanemab鈥檚 approval prospects increase, it is an open question whether the drug鈥檚 prospects for Centers for Medicare & Medicaid Services (CMS) coverage are better than those of previously approved amyloid-targeting therapies.
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By GlobalDataIn the Phase III TRAILBLAZER-ALZ 2 (NCT04437511) study, donanemab slowed disease progression in patients with high levels of tau by 29%. Tau is a small protein that builds up in the brains of patients with Alzheimer鈥檚. These results will be considered in the FDA鈥檚 final approval decision for donanemab. If approved, the therapy will join a small cohort of marketed disease-modifying Alzheimer鈥檚 drugs.
Eli Lilly鈥檚 donanemab is a monoclonal antibody (mAb) therapy that causes the immune system to remove amyloid plaques that build up in patients with Alzheimer鈥檚 disease. 鈥檚 Aduhelm and Leqembi target AD pathology in the same way.
The FDA approved Biogen鈥檚 Aduhelm (aducanumab) for treating Alzheimer鈥檚 disease in June 2021. Before this approval, no new drugs had been approved for Alzheimer鈥檚 in 18 years. In January 2023, the FDA followed this with via the accelerated approval pathway. However, in February 2023, the CMS to reconsider the agency鈥檚 decision of the coverage of mAbs that target amyloid plaques, such as Leqembi. However, with more amyloid-targeting therapies for Alzheimer鈥檚, including donanemab, approaching regulatory decisions, this issue is likely to come up again.
In an email to Pharmaceutical Technology, Philippa Salter, senior analyst at GlobalData, pointed out that this coverage stance has for the two recent major Alzheimer鈥檚 approvals. However, she also said, 鈥淭he CMS has already indicated that full approval of Leqembi could result in broader coverage, and the results from the donanemab Phase III trial add further weight that this class of drugs does have efficacy in Alzheimer鈥檚. In a market where there is nothing else disease-modifying available, pressure will increase for reimbursement for Leqembi and donanemab as drugs that have demonstrated efficacy.鈥�
Phase III donanemab data
Results from the Phase III TRAILBLAZER-ALZ 2 study showed that donanemab significantly slowed cognitive and functional decline in patients with early symptomatic Alzheimer’s disease. A cross-trial comparison suggests that donanemab gave a slightly higher efficacy compared to Leqembi with a 29% and 27% reduction in clinical decline, respectively. This was measured using the Clinical Rating-Sum of Boxes (CDR-SB) as an endpoint to measure efficacy. Based on these results, and the FDA鈥檚 accelerated approval of Leqembi in January with full approval expected to follow in July 2023, Salter says it is likely that donanemab will also gain FDA approval having demonstrated comparable efficacy.
, Lilly鈥檚 chief scientific and medical officer Dr. Daniel Skovronsky said, 鈥淭his is the first Phase III trial of any investigational medicine for Alzheimer’s disease to deliver 35% slowing of clinical and functional decline.”
Salter adds, 鈥淒onanemab requires only once-monthly dosing compared with Leqembi, which is administered every other week, therefore donanemab would provide a treatment option with less burden for patients.鈥� She also said that an approval for donanemab could affirm the for Alzheimer鈥檚, which has been controversial in the field.
Coverage of Alzheimer鈥檚 therapies
In April 2022, a decision indicated the agency was interested in answers to three questions before providing widespread coverage for mAbs directed against amyloid. The CMS stated that it would need to determine whether the therapy meaningfully improved health outcomes for patients in broad community practice, whether the therapy was associated with harms such as brain hemorrhage and edema, and how harms and benefits change over time.
After the NCD decision, CMS released a national policy for coverage of Aduhelm and any other FDA-approved mAbs for treatment of Alzheimer鈥檚 disease. , CMS announced, 鈥淢edicare will cover mAbs that target amyloid (or plaque) for the treatment of Alzheimer鈥檚 that receive traditional approval from the FDA under coverage with evidence development.鈥� However, CMS said drugs that have gone through an accelerated approval pathway or those that don鈥檛 have an established clinical benefit as per the FDA, will only receive coverage during FDA- or National Institutes of Health (NIH)-approved clinical trials. This significantly limits the accessibility of disease-modifying therapies to AD patients.
In January, launched Leqembi at a $26,500/year price, and calculated the weighted average out-of-pocket costs for Leqembi to be approximately $2 per day. Leqembi鈥檚 wholesale acquisition cost is $254.81 for the 200mg vial and $637.02 for the 500mg vial, as per GlobalData. Eisai. In December 2021, Biogen reduced Aduhelm鈥檚 wholesale acquisition cost from $56,000 per year to $28,200 at the 10mg/kg maintenance dose, after receiving negative feedback about the drug鈥檚 cost.
In released after the CMS鈥檚 initial decision to not cover Alzheimer鈥檚 Association statement, the non-profit organisation said, 鈥淔or CMS to treat those with Alzheimer鈥檚 differently than those with other diseases is unprecedented and unacceptable.鈥� It added that this move from the CMS would likely 鈥渆xacerbate and create further health inequities among those who are already disproportionately impacted by this fatal disease.鈥�
