Biohaven’s high-risk bet

There are long shots and then there is troriluzole. Biohaven will soon find out if it was wise to press on with the asset.

Investors who thought last year’s failure in Alzheimer’s had spelled the end of Biohaven’s troriluzole might be surprised to learn that the project is still in play. Phase 3 data are due before mid year in a different neurodegenerative disorder, spinocerebellar ataxia.

Biohaven hopes that its glutamate modulator will become the first approved therapy for SCA, a rare disease characterised by problems with coordination. However, the signs are not good: troriluzole previously flunked a phase 2/3 trial in this condition.

Project Troriluzole
Company Biohaven
Market cap $8.6bn
Product NPV $637m
% of market cap 7%
Event type Phase 3 trial results
Indication Spinocerebellar ataxia
Date H1 2022

Troriluzole is a prodrug of riluzole, which as Rilutek is approved for amyotrophic lateral sclerosis. The theory is that, by reducing synaptic levels of the excitatory neurotransmitter glutamate, troriluzole inhibits so-called excitotoxicity and, in turn, neurodegeneration.

However, this theory has yet to be proven. As well as failing in Alzheimer’s and SCA, troriluzole has also fallen short in obsessive compulsive disorder and generalised anxiety disorder.


In the previous SCA trial, Study 201, troriluzole did not show a benefit over placebo on the scale for the assessment and rating of ataxia (Sara) after eight weeks of treatment. Biohaven blamed a higher-than-expected placebo response (Therapy focus – No safe haven for bio in spinocerebellar ataxia, October 4, 2017).

The company has made several changes that it believes should boost its chances of success in the phase 3 Study 206.

For one, the new trial is testing a higher dose, 200mg once daily, compared with 140mg once daily in Study 201. And the latest trial will run for 48 versus eight weeks.

In addition, Study 206 uses a modified Sara score. The test measures eight outcomes to give a score of 0-40, with zero representing no ataxia and 40 most severe disease.

The modified score, however, only takes into account the first four outcomes: gait, stance, sitting and speech disturbance. According to Leerink analysts, these items correlate better with disease progression.

Another problem with carrying out trials in SCA is the fact that there are over 40 different genotypes, with different rates of disease progression. Biohaven is focusing on the SCA1 and SCA2 genotypes in Study 206; these subtypes have been shown to have “greater and more reliable decline”, Leerink noted.

A single positive pivotal study could support a US filing, given the unmet need. The SCA pipeline is sparse, and it is notable that Kissei pressed on with a filing for rovatirelin in Japan despite the failure of two phase 3 trials to show an improvement in the Sara score; the group pointed to success in a pooled analysis of severe patients.

The next project to enter the pipeline could be Seelos Therapeutics’ SLS-005, an intravenous formulation of the sugar trehalose; the group filed an IND last November with plans to start a phase 2/3 trial in early 2022.

Meanwhile, Uniqure recently deprioritised development of its preclinical SCA project AMT-150.

Even the sellside is cautious about troriluzole’s chances – Leerink puts its probability of success at 25%. But if the project does make it to market the analysts estimate peak sales of around $800m in 2030.

Biohaven, riding high after the successful launch of its migraine drug Nurtec ODT, could probably brush off a failure. An unexpected success would be a massive bonus.

The spinocerebellar ataxia pipeline
Product Company Description Details
Rovatirelin (KPS-0373) Kissei/Shionogi Thyrotrophin-releasing hormone analogue Filed in Japan; failed two ph3 studies but pooled analysis in severe pts found improvement
Troriluzole Biohaven Glutamate modulator Ph3 Study 206 data due H1 2022
Stemchymal Steminent Biotherapeutics Stem cell therapy Ph2 status unknown
CAD-1883 Novartis (via Cadent) Calcium-activated potassium channel regulator Ph2 Synchrony-1 withdrawn after Novartis pipeline assessment
Source: Evaluate Pharma &

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