The list of unpartnered amyotrophic lateral sclerosis (ALS) treatments just got smaller. Biogen Idec has snapped up the phase III-ready neuroprotective drug KNS-760704 for $20m in cash and a $60m stake in privately-held Knopp Neurosciences, allowing the partners to advance the compound into pivotal trials in the first half of next year.
As a result of the deal, KNS-760704 will join the now closely-watched olesoxime, which was cornered by Actelion earlier this month, in phase III trials for ALS. Mitsubishi Tanabe's edaravone and CytRx's arimoclomol are also in late stage studies. ALS patients currently have just one pharmaceutical treatment option, riluzole, which has modest benefits, so this deal increases the number of shots on goal for the fatal and debilitating disease. (Therapeutic focus – ALS field entering pivotal stage, August 2, 2010).
KNS-760704 is an isomer of the currently marketed drug pramipexole, sold as Mirapex and Sifrol to treat Parkinson’s disease and restless legs syndrome. Like ALS, Parkinson’s is a disease that affects the motor neurons. In Parkinson’s patients, pramipexole may act as an agonist for dopamine receptors, restoring the ability of basal ganglia to regulate motor functions.
The new agent is not the potent dopamine stimulator that prampexole is, which Knopp argues will allow patients to use higher doses. In a 90-patient open-label extension study following its phase II trial, patients were dosed at 300mg, compared with a total of 4.5mg a day for prampexole.
Like olesoxine, which appears to be the most advanced ALS drug in the R&D pipeline, KNS-760704 is a neuroprotectant. Pennsylvania-based Knopp believes orally administered KNS-760704, known generically as dexpramipexole, confers protection to neurons under oxidative stress, one of the hallmarks of ALS. Knopp itself is not sure exactly how the compound works, but its scientists have hypothesised it makes mitochondria more efficient, maintaining energy production in the cells that usually degenerate as part of ALS disease progression.
Its main phase II safety and tolerability trial tested 50mg, 150mg and 300mg doses of KNS-760704 against a placebo in 102 patients over 12 weeks, followed by 24 weeks of continued testing of 50mg and 300mg doses for 92 patients who completed the first 12 weeks. In addition to safety and tolerability, the trial also included secondary endpoints of clinical function, upright and supine vital capacity, and levels of selected proteins in blood and cerebrospinal fluid.
The initial part of the test found a dose-dependent trend in slowing the rate of disease progression using the ALS Functional Rating Scale-Revised (ALSFRS-R), and the second part found a trend toward survival benefit in the 300mg group and in a test combining mortality and functional outcomes the 300mg group had significantly improved outcomes.
Survival benefits will undoubtedly be important should KNS-760704 move to registration phase as olesoxine is being tested on survival measures. Should regulators approve olesoxine on the basis of clear survival benefit, KNS-760704 would have a harder time receiving approval based only on a functional measure such as ALSFRS-R.
Whilst EvaluatePharmadata indicate that there are currently three ALS drugs in phase III, it is not clear when edaravone results will be published, and arimoclomol is currently in a clinical hold.
Knopp’s deal with Biogen Idec calls on the Massachusetts firm to lead the development and commercialisation of KNS-760704, with Knopp supporting development and the conducting certain US commercialisation activities.
In addition to the upfront payment and share purchase, additional development, regulatory and sales milestones of up to $265m will be available along with tiered, double-digit royalties.
The company’s original investors should be happy with the deal. Knopp’s venture capital backers have stumped up $27m in two separate rounds, and the deal was struck at a high-value moment.
The price Biogen has paid upfront no doubt reflects Biogen’s confidence in the compound. Patients and ALS specialists are undoubtedly hoping such confidence is warranted.