First-quarter catalysts for the smaller players

After delving into the key clinical events due for big pharma and biotech companies, Evaluate Vantage now looks at smaller players − those with a market cap of under $2bn.

Among them, Rhythm and Supernus are gunning to expand their patient groups, while Wave Life Sciences will hope that the New Year does not start in the same way as 2020.

Wave’s shares have struggled to recover after plummeting 78% in December 2019. The company first abandoned its Duchenne muscular dystrophy project suvodirsen and then reported disappointing data with its Huntington’s disease contender WVE-120102, an antisense oligonucleotide.

Now data are due on a higher dose of WVE-120102 and a second antisense therapy for Huntington’s, WVE-120101. The readout will include results from the 32mg dose cohort that was added to both the Precision-HD1 and Precision-HD2 studies after the lacklustre results with lower doses of WVE-120102.

Topline results from Precision-HD2 showed a 12% reduction in mutant huntingtin (mHTT) protein across four doses of WVE-120102 (2mg, 4mg, 8mg and 16mg), and although theoretically a hit the result was underwhelming compared with the competition.

Tominersen, an antisense project from Roche and Ionis, has shown 40% or greater mHTT knockdown at its highest doses in early studies and is now in phase III. Phase III open-label extension data with tominersen are due by the end of the first quarter of next year and could lead to an accelerated approval filing.

Increasing numbers

Imcivree gained approval last month in two rare genetic obesity indications, but now Rhythm needs to ramp up the number of patients it can treat with the therapy.

Investors are keenly awaiting phase III data in Bardet-Biedl syndrome and Alstrom syndrome, two rare genetic disorders in which sufferers experience an insatiable hunger and severe obesity beginning early in life.

Stifel analysts note that Bardet-Biedl is the main value driver for Imcivree, with around 5,000 patients globally. As a syndromic obesity associated with intellectual impairment it is easier to diagnose than Imcivree’s first two approved indications.

The primary endpoint of the 30-patient pivotal trial is the proportion of patients who achieve a 10% or greater reduction from baseline in bodyweight after 52 weeks' treatment. The study comprises a 14-week double-blind placebo-controlled period, followed by a 38-week open-label stage; Imcivree is given by daily subcutaneous injection.

Stifel analysts believe that Imcivree only needs to demonstrate a ~20% response versus 10% for placebo for the trial to show statistical significance.

Supernus, meanwhile, is looking to expand SPN-812, a serotonin and norepinephrine modulating agent, into adults with ADHD.

The upcoming phase III is testing a flexible 200-600mg dose of SPN-812. The primary endpoint is the change from baseline in ADHD investigator symptom rating scale at six weeks.

Something to watch out for with the latest data is a potential dose-plateauing effect. In younger patients, only three out of four pivotal trials read out positively as the 600mg dose did not reach statistical significance (Supernus struggles to gain attention, March 28, 2019).

Supernus suffered a setback last month when the US FDA issued a complete response letter to the company's application for use in children and adolescents. This was not due to clinical data but instead concerned manufacturing. No new Pdufa date was provided.

Check out the table below for a full list of upcoming catalysts with consensus forecasts from EvaluatePharma. Evaluate Vantage has separately assessed expected catalysts for big pharma and biotech.