More patients with amyotrophic lateral sclerosis (ALS) had a positive response to an injection of an experimental stem cell therapy developed by Brainstorm Cell Therapeutics (BCLI compared to similar ALS patients given a placebo, according to results from a U.S. clinical trial announced Monday.

But on other efficacy measures, including change in the rate of ALS disease progression and lung function, no differences were observed between the placebo patients and those treated with Brainstorm's stem cell therapy, known as NurOwn.

NurOwn emerged from the study with a clean safety profile, so even with mixed efficacy results, there is enough scientific justification to advance the stem cell therapy into a larger, pivotal, phase III study of ALS patients, Brainstorm says.

Israel-based Brainstorm intends to meet with the U.S. Food and Drug Administration later this year to discuss a phase III study design. The company also needs to raise money to pay for the next study. 

Dr. Merit Cudkowicz, chief of neurology at Massachusetts General Hospital and the lead investigator of the NurOwn phase II study, supports Brainstorm's efforts to develop the drug further.

"Given the severity of this illness [ALS], I want to see NurOwn move forward," Cudkowicz said in a phone call last week. "This was an informative trial that provided data on safety, biological effect and possibly early signal of efficacy," she added.

Brainstorm provided me with an early look at the clinical trial results ahead of Monday's announcement, and I reached out to Cudkowicz to get her thoughts.

ALS is a progressive disease which destroys nerve cells in the brain and the spinal cord. As the disease advances, patients become paralyzed and die. About 30,000 people in the U.S. have ALS, according to the ALS Association. The drugs approved today for ALS help patients cope with symptoms but none of these stop or even slow the progression of the disease.

Brainstorm's NurOwn is made of stem cells harvested from each ALS patient. The stem cells are grown in a lab to expand their numbers and then manipulated to secrete nerve growth factors. The re-engineered stem cells are then delivered back to the ALS patient via injections into the muscles of the upper arm and the spine.

By bathing damaged neurons with stem cells secreting nerve growth factors, Brainstorm hopes to show that NurOwn can slow or halt the progression of ALS.

Brainstorm has been criticized in the past for conducting clinical trials of NurOwn in ALS which produced results which looked positive but lacked credibility. The current phase II study was designed to rigorous standards -- randomized, double-blinded and placebo controlled. Forty-eight ALS patients were enrolled at three centers in the U.S. -- Massachusetts General Hospital, UMass Medical School and the Mayo Clinic.

In a three-to-one ratio, the ALS patients were randomized to receive a single treatment with NurOwn cells or a placebo. The patients were followed for three months before treatment began to establish a disease baseline, then for another six months after their injections.

Safety was the primary endpoint of the phase II study. NurOwn was not associated with any serious adverse events and no patients withdrew from the study due to adverse events. No deaths were reported during the study. The most common adverse events reported involved fever, chills and pain at the injection sites.

More interesting to most people are the analyses comparing the efficacy of NurOwn to placebo. Here, the results were mixed.

The most common method for measuring the efficacy of ALS drugs is to track the relative progression of the disease in patients over time using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score.

When the phase II study was analyzed this way, encompassing all patients enrolled, there was a positive change in the mean ALSFRS scores benefiting NurOwn patients over placebo at two weeks post treatment. At this snapshot in the study, NurOwn looked to be working better than placebo.

However, eight weeks after treatment, NurOwn and placebo patients were progressing at the same rate of decline, measured by the mean change in ALSFRS score. At 12 and 24 weeks, the placebo patients were actually progressing a tiny bit slower than NurOwn-treated patients. The ability of NurOwn to slow ALS disease progression after a single treatment was fleeting.

Brainstorm's phase II study was also designed prospectively to compare the numbers of ALS patients who responded to NurOwn or placebo. These "responder" analyses are where Brainstorm says NurOwn demonstrated clinical benefit over placebo enough to move the therapy ahead to a phase III study.

ALS is a disease where neurons die and patients lose muscle function gradually over time. When you plot the course of a patient's ALS on a graph using the ALSFRS score, the line slopes down to the right. Any drug that can flatten the slope of the ALSFRS curve over time, or even cause the slope of the line to go up, would be slowing the progression of the disease.

In Brainstorm's U.S. study, a patient was declared a responder if the slope of their ALSFRS curve went from negative before treatment to flat or positive after treatment.

At two weeks post treatment, 74% of NurOwn patients were responders, compared to 46% of placebo patients.

At eight weeks, the difference narrowed to where there was basically no difference in the response rates between NurOwn and placebo.

But at 12 weeks, 28% of NurOwn patients were still responders compared to just 8% of placebo patients. At 24 weeks, the end of the study, four NurOwn patients (11%) remained responders while all of the placebo patients had progressed. There were zero placebo responders.

Brainstorm applied the responder analysis in different ways to the study data but all showed a consistent benefit favoring NurOwn over placebo.

Cudkowicz, the study's principal investigator, told me the positive responder analysis is not definitive proof that NurOwn works in ALS, but it's a clinically meaningful signal that deserves to be fleshed out in a larger phase III study.

Brainstorm's announcement Monday includes supportive quotes from the study's other two investigators, but I could not reach them for independent comment.

The design of the phase III study has not been finalized, but the company says it will likely mimic the phase II study but with more patients and perhaps a more narrowly defined ALS population. The study will enroll patients in the U.S. and include some kind of blinded control arm.

Most importantly, the next study will treat patients with multiple doses of NurOwn instead of the single treatment used in the phase II. That's because the data from the phase II study suggest the NurOwn stem cells don't persist long enough without replenishment. How many doses will be required has not been decided but Cudkowicz believes every 8-12 weeks seems likely.

As of March 31, Brainstorm had $13 million in cash. The company will need to raise additional money to fund the next NurOwn study.

Brainstorm closed Friday at $2.99 per share. 

Adam Feuerstein writes regularly for TheStreet. In keeping with company editorial policy, he doesn't own or short individual stocks, although he owns stock in TheStreet. He also doesn't invest in hedge funds or other private investment partnerships. Feuerstein appreciates your feedback; click here to send him an email.