KISUNLA: Another breakthrough for Alzheimer’s Disease patients
One of the biggest stories to hit the pharma news this week was the FDA full approval of KISUNLA (donanemab, Eli Lilly) for the treatment of Alzheimer’s Disease (AD). Along with LEQEMBI (lecanemab, Eisai/Biogen), this brings the total number of disease modifiers active in the market to two, after the failed launch of ADUHELM. So the key question everyone is asking is how does KISUNLA compare to LEQEMBI? We’ll dig into this shortly.
Despite the great progress, much more remains to be done. This gives plenty of scope for new disease modifying treatments to make their mark. We’ll cover this towards the end of this post.
No clear winner between KISUNLA and LEQEMBI
So how do the two main treatments compare? In many ways the drug labels are very similar. Both are indicated for patients with mild cognitive impairment and mild dementia in AD (1), both require confirmation of the presence of amyloid beta pathology before treatment and both require multiple MRI scans prior to and during the course of treatment.
Both drugs showed statistical improvements in cognition
- KISUNLA: 22% improvement compared to placebo at 76 weeks on the Integrated Alzheimer’s Disease Rating Scale (iADRS)
- LEQEMBI: 27% improvement compared to placebo at 18 months on the Clinical Dementia Rating Sum of Boxes (CDR-SB)
Given the differences in study end points, it is hard to draw a direct comparison on efficacy between the two drugs.
Regarding safety, a key question is how do both drugs perform on ARIA (amyloid-related imaging abnormalities). Both drugs carry warnings on the potential effects of ARIA related to the drugs. Here it appears as if LEQEMBI performs better, having been observed in 21% of study subjects treated with the active drug compared to 36% for KISUNLA (including symptomatic and asymptomatic ARIA events, ARIA-E and ARIA-H). (1)
One of the most significant differences between the two products is the stopping criterion for KISUNLA. Once there is evidence from amyloid PET imaging to show amyloid has been reduced to minimal levels, there is an option to stop treatment. This information does not exist in the LEQEMBI label resulting in uncertainty around how long patients need to be treated. Stopping criteria will help HCPs, Patients and in particular Payers to manage the administration and cost of these drugs.
Another area of important difference is in the dosing schedules, which is likely to give KISUNLA the advantage. KISUNLA requires monthly IV infusions for approximately 30 minutes at a time. This compares to fortnightly dosing of an hour each time for LEQEMBI. This could result in significant savings for health providers, where infusion centers currently have capacity constraints, as well as greater convenience for patients.
Price wise, KISUNLA is looking to be the more expensive drug with a list price of $32,000 per year, compared to $26,500 for LEQEMBI (prices prior to any non-disclosed discounts). As most patients will be covered by Medicare, which prohibits patient coupons to offset co-pays, this price difference is likely to be influential in the choice of treatment. (2)
Much more to be done …
Whilst great progress has been made in bringing disease modifiers to AD patients, there remains a lot of work to do.
1. Reducing the rate of decline further:
The approved drugs have the effect of reducing the decline rather than halting disease progression. In addition, the changes relative to placebo are small on the overall scale of cognition. We will need to see longer term data to understand the full impact in the later stages of the disease. In addition, it may be that these treatments need to be combined with drugs having other mechanisms of action to obtain slower rates of decline.
A recent report from Spherix found that only a “few surveyed neurologists consider Leqembi to be a significant medical advance over other historical AD treatments” (3). These views may spill over to the whole class of amyloid targeting drugs, potentially affecting uptake of KISUNLA as well.
2. Easing pricing and market access constraints:
Many patients are struggling to get access to LEQEMBI with 40% of eligible patients not able to secure approval from their health plan. Further barriers exist due to high copays. (3)
In its public meeting in March last year, the Institute of Clinical and Economic Review (ICER) reported that its independent appraisal committee felt that the “currently available evidence is not adequate to demonstrate a net health benefit for lecanemab when compared to supportive care… lecanemab would achieve common thresholds for cost-effectiveness if priced between $8,900 - $21,500 per year”
Given this, it is likely that pricing and access will remain key factors across the whole drug class for some time yet.
3. Further differentiation within the drug class:
A wide range of drugs and novel mechanisms of action are in development for AD, a topic for another post sometime soon. However, a key point within the amyloid beta class is further differentiation amongst the molecules themselves; in particular, which type of amyloid beta is being targeted. Acumen Pharmaceuticals for example is developing Sabirnetug which targets amyloid beta oligomers instead of the amyloid plaques targeted by the approved drugs. Acumen argues that these oligomers are more toxic and damaging to neurons, thereby opening the potential to improve clinical outcomes. Sabirtenug is about to commence its phase 2 study, the results of which will help shed light on this hypothesis. (5)
Conclusion
Overall, the KISUNLA approval is another great step forward in improving the lives of patients with AD. Notable differences exist between KISUNLA and LEQEMBI in terms of safety, dosing and economics meaning there does not appear to be an overall winner. Despite these advances there is still much work to be done to improve access to treatments and outcomes.
Contact
If you are interested in discussing any of the issues above for your company/drug development program, please contact me through my email address dniven@nivenbiopharma.com . Feel free to also visit my website at www.nivenbiopharma.com for more information.
I have no conflicts of interest in the production of this article.
References:
- FDA Drug labels (LEQEMBI, KISUNLA)
- Game on: Lilly's Alzheimer's drug Kisunla, a challenger to Biogen and Eisai's Leqembi, gains full FDA nod, Fierce Pharma 2 July 2024
- Neurologists Report Frustration with Efficacy and Logistical Issues Around Eisai/Biogen’s Leqembi, According to Spherix Global Insights Neurologist Survey, Spherix, February 2024
- Alzheimer’s Disease, An Assessment of Lecanemab, Institute for Clinical and Economic Review, March 2023
- Acumen Pharmaceuticals website
