Neuraltus Pharmaceuticals said today it is weighing if, and how, it plans to continue developing its lead candidate NP001 after it failed a Phase II confirmatory study in amyotrophic lateral sclerosis (ALS) patients with elevated levels of systemic inflammation—a review that makes the drug unlikely to be the third approved treatment for the disease any time soon, if ever.

NP001 missed its primary and secondary endpoints in the confirmatory study, designed to replicate an earlier Phase II study assessing the drug in ALS patients with elevated levels of baseline inflammation.

The confirmatory study (NCT02794857) was a randomized, double-blind, placebo-controlled, multicenter study that enrolled 138 ALS patients with evidence of systemic inflammation at 22 sites across North America. Patients were randomized to either NP001 2 mg/kg or placebo over six months. The study was funded in part through a $1.5 million grant from The ALS Association, announced in 2015.

The trial’s primary endpoint was change from baseline of an individual's ALS Functional Rating Score Revised (ALSFRS-R) during the six-month study period. Secondary endpoints were change in pulmonary function, as measured by vital capacity readings; time to tracheotomy; and change in levels of blood inflammatory biomarkers.

Neuraltus said topline data from the study will be presented today during a podium presentation at the American Academy of Neurology's 70th Annual Meeting in Los Angeles.

“We are conducting additional analyses of the trial results to determine if and how we will proceed in developing the compound,” Neuraltus CEO Rich Casey said in a statement.

NP001 is the only drug listed in the pipeline of privately held Neuraltus, which is based in San Bruno, CA. NP001 has completed Phase I development for Alzheimer’s disease and has been in preclinical phases for frontotemporal dementia.

As for ALS, the original Phase II study Neuraltus completed in 2012 (NCT01281631) compared the safety, tolerability, and preliminary efficacy of two dose levels of NP001 versus placebo using the ALSFRS-R. 

Last year, Neuraltus said that a secondary analysis of study results suggested that patients more likely to respond to NP001 could be determined based on increased levels of a biomarker for systemic inflammation, C-reactive protein (CRP).

A post hoc analysis of the earlier trial showed that the 2 mg/kg dose of NP001 slowed ALS progression compared with placebo based on changes from baseline of ALSFRS-R (57%, p<0.02) and vital capacity (66%, p<0.03) in patients with elevated systemic inflammation (CRP>0.1125 mg/dL), according to an abstract of today’s presentation.

“We recognize the desperate need for advances in treating ALS and are very disappointed with the findings in our confirmatory Phase II study of NP001,” said Casey.

According to the ALS Therapy Development Institute, more than 30,000 people live with ALS in the U.S. at any given time, while the number worldwide is estimated at around 450,000.

Only two ALS therapies have been approved by the FDA. The first was Rilutek® (riluzole), approved in December 1995 and available as a generic since 2013. Last year, the FDA authorized the second therapy, Radicava® (edaravone), launched last year by Mitsubishi Tanabe Pharma. Radicava generated ¥6.4 billion ($58.6 million) in sales last year, the company disclosed in February.

However, Radicava is costly. According to the ALS Association, the drug carries a list price of $1000 per infusion and $11,000 per dosage cycle, which amounts to $146,000 per year. But those prices do not include coverage from insurance or Medicare/Medicaid, and Mitsubishi Tanabe Pharma says it offers co-pay assistance for commercially insured patients.

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