- Results from an early-stage trial released Thursday by Ionis Pharmaceuticals Inc. show why Swiss pharma Roche AG was eager to license the biotech's experimental candidate for Huntington's disease two months ago.
- Patients given Ionis' treatment, a so-called antisense drug, experienced a dose-dependent reduction in the mutant protein that drives progression of the neurodegenerative disease. Adverse events were mild and no participants discontinued the trial.
- Roche, now in charge of leading development, plans to push the drug into a pivotal study which will test how the protein-lowering effects translate to functional benefits for Huntington's patients.
Not content to rest on the success of Spinraza (nusinersen), Ionis has moved quickly to capitalize on its broad pipeline of antisense drugs. The biotech filed for U.S. approval of its wholly owned candidate for TTR amyloidosis in late 2017, and has advanced half a dozen drugs toward Phase 2 readouts this year.
Most of its candidates are in development together with a big pharma partner, like Biogen Inc. in neurology.
Data released March 1 on RG6042, Ionis' only neuroscience candidate not licensed to Biogen, back Roche's decision to pay a $45 million licensing fee to gain exclusive rights to the drug.
In the 46-patient Phase 1/2 study, patients were given one of five doses of RG6042 or placebo. Encouragingly, results showed a dose-dependent response to treatment. Patients who received either the 90 mg or 120 mg dose of RG6042 experienced an average drop in the levels of mutant huntingtin protein of 40%, with some individuals seeing reductions as high as 60%.
Due to a genetic mutation, patients with Huntington's produce an abnormal form of the huntingtin protein, or mHTT, which damages neurons and leads to mental and physicals deterioration over time. Reducing levels of this protein, therefore, should help slow or alter the disease's progression.
"In this study, we were able to achieve mutant huntingtin protein reductions in study participants that were higher than those that produced disease benefit in preclinical models of HD," said C. Frank Bennett, head of neurological programs at Ionis, in a prepared statement.
Data from the rodent and non-human primate models Bennett referred to showed a 40% to 60% lowering of mHTT in the cerebrospinal fluid led to a corresponding reduction in both the cortex and caudate regions of the brain.
"We remain encouraged by this program and expect interest to continue to grow as the data evolve and mature," wrote Evercore ISI analyst Josh Schimmer in a March 1 note to investors.
Patients who participated in the Phase 1/2 study will continue to receive treatment through an open-label extension of the trial.