MS trial halted as antihistamine produces worrying results

A potential breakthrough in multiple sclerosis (MS) treatment took a surprising turn as a clinical trial on an over-the-counter antihistamine, clemastine fumarate, had to be halted due to worrying effects on some participants.

Clemastine fumarate had previously shown promise in animals studies as being helpful in remyelination, but showed a starkly different outcome in humans, with three participants experiencing a significant fivefold increase in disease progression.

The abrupt cessation of this arm of the trial, led by the National Institute of Allergy and Infectious Diseases (NIAID) in the US, came as a shock to researchers following initial optimism surrounding the inexpensive antihistamine’s potential in treating MS. Some patients had been reportedly using clemastine fumarate off-label based on early encouraging findings.

Presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2024, the trial’s results painted a cautionary tale. Despite promising indications from mouse studies and a small clinical trial suggesting clemastine’s ability to promote myelin repair, the reality proved different in human subjects.

Clemastine fumarate was one of four drugs under investigation in the ongoing TRAP-MS phase 1/2 trial sponsored by NIAID. The study aimed to evaluate the effects of these drugs on MS biomarkers, both individually and in combination. Alongside clemastine fumarate, the trial included pioglitazone (Actos), dantrolene (Ryanodex, Revonto, and Dantrium), and pirfenidone (Pirespa).

Initial enrolment expectations for the trial were high, with an estimated 250 adults with MS anticipated to participate. However, the unexpected adverse effects observed in the clemastine arm raised red flags, prompting a re-evaluation of the drug’s potential benefits and risks.

Per the study protocol, nine patients in the clemastine arm received 8 mg/d, divided into three doses. Cerebrospinal fluid samples were collected at baseline and after six months of treatment. The three patients who experienced accelerated disability progression exhibited elevated levels of C-reactive protein and erythrocyte sedimentation rate, along with weight gain indicative of a systemic pro-inflammatory state, according to study authors.

The findings underscore the complexities of translating promising preclinical research into effective treatments for MS and highlight the importance of rigorous clinical trials to assess safety and efficacy in human subjects.