Upcoming events – Adamas and Ascendis look for new paths forward

Adamas hopes to make Inroads with Gocovri in MS, while Ascendis will report data for Transcon PTH in hypoparathyroidism.

Welcome to your weekly roundup of approaching clinical readouts. In the fourth quarter Adamas Pharmaceuticals is due to report data with Gocovri in multiple sclerosis as it seeks to find new avenues of growth for its marketed drug.

A lacklustre launch in Parkinson’s dyskinesia, for which the product was approved in 2017, has led to dwindling sales forecasts, and the company’s shares have suffered a similar fate (Adamas confirms that solo launches are best avoided, March 5, 2019).

The phase III Inroads study is evaluating Gocovri in MS patients with walking impairments. The primary endpoint is the proportion of responders, defined as those with a 20% or greater improvement in the timed 25-foot walk at week 12. Evercore analysts note that powering assumes around a 33% response rate in the active arm, versus 20% with placebo.

Adamas has said a second phase III trial in MS gait will likely be needed for approval. If Gocovri gets the nod it would be up against Acorda’s Ampyra, another therapy used to improve walking in MS. 

With generic versions of Ampyra already available, Gocovri could find it tough to gain market share. Adamas’s initial focus will be patients who have discontinued Ampyra; around half of the patients in Inroads are Ampyra failures. But in order to sell really well, Gocovri will need to show markedly better efficacy than Ampyra. In one of its pivotal trials, the Acorda drug improved walking speed by 14% versus 8% with placebo at nine weeks. 

The omens are not good: phase II data with Gocovri show a similar 17% improvement in walking speed at four weeks, although the usual caveats about cross-trial comparisons apply.

According to consensus from EvaluatePharma Gocovri sales are forecast to reach $357m by 2024 with the MS indication making up $120m of the total. At its peak Ampyra had sales of $635m.

Trial

Details

NCT03436199 (Inroads)

Oral 137mg or 274mg Gocovri/ADS-5102 versus placebo. 2-week up-titration phase, 10-week maintenance phase.

NCT03567057

Open-label extension, 52 weeks.

Ascendis’s Path Forward

Also due in the fourth quarter are data from Ascendis’s phase II Path Forward study with Transcon PTH, its treatment for the rare disease hypoparathyroidism. Insufficient levels of parathyroid hormone can cause symptoms including muscle twitching and pain, and tiredness and mood changes. 

The study is testing Transcon PTH plus standard of care – oral calcium and vitamin D – versus standard of care alone in 40 patients. The aim is to taper patients off vitamin D and decrease calcium supplements. The primary endpoint is a composite measure of the proportion of patients who achieve a normal serum calcium level, significant reduction in calcium and vitamin D needs, and normal urinary calcium or a reduction in urinary calcium, at four weeks. 

Takeda’s Natpara, a replica of human parathyroid hormone, became the only approved drug in the US for hypoparathyroidism when it got the nod in 2015; however, it comes with safety concerns including hypo- or hypercalcaemia and a black box warning for osteosarcoma, and is only available through a restricted REMs program.

Natpara also leads to variable levels of parathyroid hormone throughout the day, something that Transcon PTH, a long-acting prodrug of parathyroid hormone, aims to address.

According to consensus from EvaluatePharma, Natpara is forecast to bring in 2024 sales of $380m, versus just $186m for Transcon PTH. The Evercore analysts are vastly more bullish, saying the market for Ascendis’s drug could top $1bn if it succeeds.

Ascendis will still need to carry out phase III trials, but the Path Forward data should at least show whether it is going in the right direction.

Trial

Details

NCT04009291 (Path Forward)

15, 18 or 21µg/day versus placebo, 4 weeks treatment. All subjects may then enter a longer term extension where doses will be individually optimised.

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