Highlights from

AAN 2019

American Academy of Neurology annual meeting

Philadelphia, USA 4-10 May 2019

New compounds for MS treatment

Phase-1 and phase-2 results of a couple of new compounds against MS were presented at the AAN 2019 meeting.

Elezanumab

Elezanumab is a fully humanised monoclonal antibody directed against repulsive guidance molecule A (RGMa). In a phase 1, double-blind, placebo-controlled, randomised, escalating multiple-dose study, elezanumab was well-tolerated and did not consistently result in symptom worsening in patients who received multiple doses of up to 1,800 mg [1].

A total of 20 MS patients (2 with SPMS) were randomised to 150 mg, 600 mg, or 1,800 mg elezanumab or to placebo. The most common AE was headache (25% of patients); 3 patients had a relapse. Free soluble RGMa decreased with increasing levels of elezanumab in CSF, while total RGMa increased linearly with CSF elezanumab exposure. Two phase 2 studies are on their way: RADIUS-R and RADIUS-D, for relapsing MS and progressive MS patients, respectively.

Evobrutinib

Evobrutinib is a highly specific oral inhibitor of Bruton’s tyrosine kinase (BTK), a key regulator of B cell and macrophage functions implicated in MS. This is the first BTK inhibitor demonstrating reduction of disease activity in an autoimmune indication [2].

In a double-blind phase 2 study, 267 adult relapsing MS patients were randomised to evobrutinib 25mg QD, 75mg QD, 75mg BID, open-label dimethyl fumarate (240 mg BID; reference arm), or placebo for 48 weeks. Placebo-treated patients switched to evobrutinib 25mg QD after 24 weeks. Evobrutinib 75mg QD and BID significantly reduced the total number of T1Gd+ lesions at week 12, 16, 20, and 24 versus placebo, which was the primary endpoint. There was a significant dose response (P=0.001).

Liothyronine

In a phase 1b open-label study, liothyronine (synthetic tri-iodothyronine: T3) appeared safe and well-tolerated in 20 patients with relapsing or progressive MS [3].

T3 is a licensed product most commonly used to treat hypothyroidism and myxoedema coma. The rationale for using it in this study was that thyroid hormones play a role in early CNS development including promotion of myelination. In animal studies, T3 regulated oligodendrocyte differentiation and maturation. Every participant received T3 according to a standardised dose-titration schedule. The primary endpoints were safety and tolerability. Most common adverse events included gastrointestinal distress and abnormal thyroid function tests; no clinical thyrotoxicosis occurred. T3 was overall well-tolerated without treatment-related severe or serious adverse events. A larger trial will help assess whether it promotes oligodendrogenesis and enhance remyelination in vivo, limits axonal degeneration/apoptosis, and improves function.

  1. Ziemann A, et al. AAN 2019, S56.001.
  2. Montalban X. et al. AAN 2019, S56.004.
  3. Newsome S, et al. AAN 2019, S56.003.

Top image: © iStockPhoto: Eraxion

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.