Pharmaceutical Technology

FDA approves Eli Lilly’s Kisunla (donanemab) for early AD

Leqembi and Kisunla could generate global sales of $3.5 billion and $2 billion respectively by 2030.

Eli Lilly announced on 2 July 2024 that the US Food and Drug Administration (FDA) has approved its anti-amyloid beta (Aβ) monoclonal antibody (mAb) Kisunla (donanemab) for the treatment of patients with mild cognitive impairment or mild Alzheimer’s disease (AD). The approval came on the final day of the 10th Congress of the European Academy of Neurology and followed an earlier delay when, instead of providing an approval decision in March, the FDA instead decided to convene an advisory committee to review the drug. It received a unanimous favourable opinion from the committee in June.

The approval of Kisunla was based on data from the Phase III TRAILBLAZER-ALZ 2 trial (NCT04437511). Kisunla-treated patients demonstrated a 35% slowed cognitive and functional decline compared with placebo-treated patients after 18 months, as measured by the primary endpoint, the integrated AD Rating Scale. Kisunla is the second disease-modifying therapy (DMT) to reach the AD market in the US, providing competition for Eisai/Biogen’s anti-Aβ mAb Leqembi (lecanemab), which received full FDA approval in July 2023.

Despite approval in mid-2023, uptake of Leqembi has been slow. While the approval of Kisunla will provide further confidence in the anti-Aβ mAbs, which could help drive the uptake of both drugs, many of the challenges faced by Leqembi will also apply to Kisunla. Both drugs require the presence of amyloid pathology to be confirmed via a positron emission tomography (PET) scan to assess levels of amyloid in the brain before treatment initiation.

Monthly dosing gives Kinsunla a competitive advantage

A magnetic resonance imaging (MRI) scan is required before treatment, with further MRIs recommended before subsequent infusions. For Kisunla, an MRI should be obtained before the 2nd, 3rd, 4th and 7th infusions, compared with the 5th, 7th and 14th for Leqembi. Access to PET and MRI scans is a key economical and operational limiting factor for the uptake of these drugs as healthcare systems adjust to the addition of these DMTs to the treatment paradigm.

A known side effect of the anti-Aβ mAb drug class is the development of amyloid-related imaging abnormalities (ARIAs), including ARIAs related to underlying vasogenic oedema (ARIA-E). For Leqembi, the rate of ARIA-E in Clarity AD (NCT03887455) was 12.5% and the rate of symptomatic ARIA-E was 2.8%. For Kisunla in TRAILBLAZER-ALZ 2, the rate of ARIA-E was 24% and the rate of symptomatic ARIA-E was 6.1%. This is also reflected in the labels for both drugs, with enhanced clinical vigilance for ARIA recommended during the first 24 weeks of Kisunla treatment compared with just the first 14 weeks of Leqembi treatment. The favourable safety profile of Leqembi will give the drug a key advantage as it begins to face competition from Kisunla, and this advantage was consistently highlighted by key opinion leaders previously interviewed by GlobalData when discussing the two drugs.

17% of patients were able to complete treatment at six months

However, an important competitive advantage for Kisunla is its once-monthly dosing schedule compared with Leqembi’s dosing of once every two weeks. Despite having a higher annual cost of therapy of $32,000 for Kisunla compared with $26,500 per year for Leqembi, Lilly states that in the long term, Kisunla will be cheaper and more convenient for patients since they won’t have to take the drug indefinitely, something that was included in the FDA label, which states that once amyloid plaques have been reduced to minimal levels on PET imaging, cessation of treatment can be considered. During the TRAILBLAZER-ALZ 2 trial, 17% of patients were able to complete treatment at six months, 47% at 12 months and 69% at 18 months. While there are clear advantages in not having to take a drug indefinitely, many questions have been raised about what happens once Kisunla therapy is stopped, and how easy monitoring amyloid levels will be in the real world with the high cost and limited availability of PET scans. Further real-world evidence and clinical trial data will be key for physicians to feel confident in stopping treatment with Kisunla, which will be vital for the success of the drug.

GlobalData forecasts that Leqembi and Kisunla could generate global (China, France, Germany, Italy, Japan, Spain, the UK and the US) sales of $3.5 billion and $2 billion respectively by 2030.