Eisai Closes Door on Lorcaserin Program for Dravet Syndrome

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Key Takeaways

Eisai discontinued lorcaserin trials for Dravet syndrome due to recruitment challenges, exacerbated by fenfluramine's availability.
Patients were required to stop lorcaserin by October, with no further access, impacting those relying on it for seizure control.
Lorcaserin, a 5-HT2c receptor agonist, was withdrawn due to cancer risks but continued off-label for Dravet syndrome under expanded access.
MOMENTUM 1 aimed to assess seizure frequency changes and responder rates, with pharmacokinetic analyses planned.

The launch of lorcaserin studies in 2020 coincided with several patients starting the newly available fenfluramine, which may have contributed to challenges in enrolling enough participants.

Eisai has discontinued 2 clinical trials for lorcaserin in Dravet syndrome due to recruitment challenges in this rare epilepsy. The affected trials include the phase 3 MOMENTUM 1 study (NCT04572243) and MOMENTUM 2 extended access program, as first reported by the Dravet Syndrome Foundation (DSF) in August.^1,2

According to the foundation, patients were asked to stop lorcaserin by October to complete final study visits, with no further access to the drug afterward. The DSF has engaged with Eisai to understand the situation and explore alternatives, recognizing the significant challenge for families who relied on lorcaserin as an effective antiseizure treatment after other medications failed.

Issues with the trial stem from recruitment, according to the DSF, and the lack of ability to gather large enough data to evaluate lorcaserin as a potential treatment for DS. The studies were initiated in 2020, around the time that the FDA approved fenfluramine (Fintepla; UCB) as a new treatment for DS. All told, the launch of the lorcaserin studies coincided with many patients starting the newly available fenfluramine, which may have contributed to challenges in enrolling enough participants.

MOMENTUM 1, which originally had a target enrollment of 58 patients with DS, was planning on using change in the frequency of convulsive seizures over a 28-day period as the primary end point. Additionally, the study also employed percentage of 50% responders with convulsive seizures as a secondary outcome measure. Investigators had planned on conducting pharmacokinetic analyses as well, describing the relationships between lorcaserin plasma concentrations and efficacy and safety.

Lorcaserin, a selective serotonin 5-HT2c receptor agonist, was previously marketed as Belviq by Eisai as an FDA-approved weight-loss drug. In February 2020, Eisai voluntarily withdrew the medication at the request of federal regulators after data from the CAMELLIA-TIMI 61 trial revealed an increased risk for cancer in treated patients.³ Following the withdrawal, the company noted that it received multiple requests from patients, caregivers, and health care professionals for continued access to patients who were prescribed Belviq off-label to help treat DS, as well as other refractory epilepsies.⁴

The added requests prompted a consultation with the FDA, who then agreed with Eisai about the importance of patient access to lorcaserin for DS, to the extent of each individuals’ health care provider’s belief in continued access as medically appropriate. As a result, the company was able to continue with MOMENTUM2, a centralized expanded access program that includes patients with DS and other refractory epilepsies who were prescribed lorcaserin by their treating physician prior to the market withdrawal.

In MOMENTUM 1, patients aged 2 or older with DS were randomly assigned to receive weight-based doses of lorcaserin oral suspension twice daily for 14 weeks. Eligibility required at least 4 convulsive seizues during a 4-week baseline, stable antiepileptic drug regimens, and no recent use of lorcaserin (4 weeks) or fenfluramine (2 months). Patients on serotonergic drugs, monoamine oxidase inhibitors, or with other progressive central nervous system diseases were excluded.

REFERENCES
1. Eisai officially winds down epilepsy programme. FirstWord Pharma. November 18, 2024. Accessed November 27, 2024. https://firstwordpharma.com/story/5913501
2. Discontinuation of studies and manufacturing of lorcaserin. Dravet Syndrome Foundation. News release. August 2, 2024. Accessed November 27, 2024. https://dravetfoundation.org/discontinuation-of-studies-and-manufacturing-of-lorcaserin/
3. Eisai to voluntarily withdraw Belviq in the U.S. Eisai. February 13, 2020. Accessed November 27, 2024. https://www.prnewswire.com/news-releases/eisai-to-voluntarily-withdraw-belviqbelviq-xr-in-the-us-301004885.html
4. Eisai initiates phase 3 MOMENTUM1 clinical trial (study 304) of lorcaserin in Dravet syndrome. News release. Woodcliff, NJ: Eisai. September 30, 2020. Accessed November 27, 2024. https://www.prnewswire.com/news-releases/eisai-initiates-phase-3-momentum-1-clinical-trial-study-304-of-lorcaserin-in-dravet-syndrome-301141831.html