Welcome to your weekly digest of approaching regulatory and clinical readouts. Raptor Pharmaceutical’s (NASDAQ:RPTP) efforts to expand the reach of Procysbi are approaching another milestone with the release this quarter of interim data from a phase II/III study in inherited mitochondrial diseases.
The main excitement over The Medicines Company (NASDAQ:MDCO) has been for its anti-PCSK9 agent but this could soon change, with news on another cardiovascular project, MDCO-216, expected mid-year. Interim data from a phase II trial could give an indication of whether the agent reduces plaque in heart attack patients.
Procysbi’s sales have so far disappointed, and its failure last autumn in the CyNCh trial in paediatric fatty liver disease has raised the stakes (Latest failure makes Raptor more affordable, September 14, 2015). Raptor needs a hit.
The MITO-001 trial might provide one. It has aimed to recruit around 32 children with a range of extremely rare mitochondrial disorders associated with DNA mutations. It is not clear exactly which conditions the trial patients have, but its listing on Clinicaltrials.gov states that around two-thirds of subjects are expected to have Leigh syndrome.
Leigh syndrome is a severe neurological disorder that manifests in the first year of life. It is characterized by progressive loss of mental and movement abilities and typically results in death within a couple of years, usually due to respiratory failure.
Other diseases listed as suitable for inclusion in the trial include Leber’s hereditary optic neuropathy, myoclonic epilepsy with ragged red fibers and Kearn-Sayre syndrome.
The trial has a drawback in that it does not have a control group, and thus will probably not be enough to secure approval for Procysbi in mitochondrial disorders, analysts from Oppenheimer believe. They write that the study’s primary endpoint, change on the Newcastle Pediatric Mitochondrial Disease Scale, is highly subjective, and regulators are likely to require a placebo-controlled study.
Still, Procysbi is the most advanced drug for mitochondrial disorders. With the exclusivity that would greet an approved drug in an orphan indication success in MITO-001 could up the product’s sales significantly. Investors will be watching the results of the trial to get a sense of whether Raptor can get past the FDA’s fences.
Both assets are important to the company as it aims to make the transition from a hospital-based business to a multi-product biotech (Interview – Medicines Company looks away from the hospital bed, September 8, 2015).
There are no consensus forecasts yet for MDCO-216, but Leerink analysts believe it has blockbuster potential. First, it needs to show it can reduce percentage atheroma volume, the primary endpoint of the phase II trial, measured using intravascular ultrasound. Data are due soon from 40 patients, while a final analysis on all 120 patients is expected later in the year.
Success will permit the start of a phase III trial in over 5,000 patients. TMC might not be able to afford to carry out such a large study alone, raising the issue of finding a partner – or, as rumored in January, a buyer.
However, potential acquirers might be chary of lingering uncertainties around the cholesterol-lowering strategy, not helped by the recent failure of Lilly’s (NYSE:LLY) CETP inhibitor evacetrapib to prevent cardiovascular deaths or hospitalizations, despite the fact that it lowered “bad” LDL cholesterol and increased “good” HDL cholesterol (ACC – All eyes on Merck as evacetrapib data underwhelm, April 4, 2016).
MDCO-216 has a different mechanism of action, being a variant of the apolipoprotein A1 protein known as ApoA-I Milano, which has been linked with lower cardiovascular risk. But victory is not a given – the Leerink analysts only give the project a 20% chance of success.