Two ALS Drugs Show Early Promise

The experimental drugs  KNS760704 and SB509 both appear safe and show hints of effectiveness.

by Margaret Wahl on December 9, 2009 - 5:25pm

Two experimental compounds under development by different drug companies have shown encouraging early results,  according to reports given at the 20th International Symposium on ALS/MND in Berlin.


The experimental drug KNS760704, developed by Knopp Neurosciences of Pittsburgh, was found to be safe and well tolerated, and showed indications of possible benefit in 92 people with ALS who took it for a total of nine months.

These positive results from the two-part, phase 2 trial could mean that KNS760704  will enter phase 3 testing in the near future.

Results were announced Dec. 9, 2009, at the 20th International Symposium on ALS/MND in Berlin.

Study investigator Merit Cudkowicz, who directs the MDA/ALS Center at Massachusetts General Hospital in Boston, reported the results at the ALS/MND symposium in Berlin. Although she did not receive MDA support for this study, which was funded by Knopp Neurosciences, she has received and continues to receive significant MDA support for ALS research.

About KNS760704

According to Knopp, KNS760704 appears to protect nerve cells under stress. The experimental drug is a molecular mirror image of pramipexole, a prescription medication approved for the treatment of Parkinson's disease and restless legs syndrome under the trade names Mirapex and Sifrol. The company says these two mirror-image molecules have very different properties.

About the KNS760704 trial

The study ran for three months followed by a one-month break, followed by more six months.

In part 1, 102 people with ALS were randomly assigned to receive daily doses of 50, 150 or 300 milligrams of KNS760704 or a placebo for three months. There was a trend toward a slowing in the rate of disease progression, as measured by the ALS Functional Rating Scale, across all treatment groups, with greater benefit correlated with higher dosage levels. ("Trends" are results that suggest an effect but can't be called "significant," because they don't reach mathematical criteria for statistical significance.)

In part 2 of the study, which followed a one-month "washout" period, 92 of the original trial participants were randomly assigned to receive either 50 or 300 milligrams per day of KNS760704 for an additional six months. There was a dose-related trend toward a slowed rate of disease progression, and there also was a trend toward a survival benefit in the 300-milligram group compared to the 50-milligram group.

Cudkowicz said the safety results and the trends toward improved functional and survival outcomes observed in this study provide preliminary evidence supporting the ongoing evaluation of KNS760704 in phase 3 (large-scale) clinical trials.

KNS760704 trial participation

When available, information about participating in this trial will be posted on the MDA site and in MDA's ALS Newsmagazine.

SB509 modestly improves muscle strength

A report given at the symposium about trials of the experimental compound SB509 suggests the substance is safe and well tolerated and also may have a positive effect on function in people with ALS.

SB509 is being developed by Sangamo Biosciences, a Richmond, Calif., biotechnology company, which funded this phase 2 trial.

The compound contains the gene for an activator of a protein called vascular endothelial growth factor A (VEGF A). VEGF A protein increases production of blood vessels and may protect or nourish nerve cells.

In people with ALS, VEGF A levels in the spinal fluid are lower than normal, and receptors (docking sites) for VEGF are increased in blood vessels and in the spinal cord, perhaps because the body attempts to compensate for the lower VEGF protein levels.

About the SB509 trial

Forty-five people with ALS are enrolled in the partially completed phase 2 trial, and the symposium report included data from 22 of them.

All trial participants are being treated with SB509. They're being compared to a “historical” control group -- untreated ALS patients who may have been in a placebo group in other trials but are not enrolled in this trial.

Four months after treatment with SB509, six out of 19 people (32 percent) showed improvement on manual muscle testing scores. These trial participants each received two sets of SB509 injections into the neck, arms and legs, three months apart.

In the historical control group, 26 out of 153 (17 percent) showed improvement on manual muscle tests.

Five of the six people treated with SB509 who showed improvement with manual muscle testing also improved on the ALS Functional Rating Scale, which assesses physical abilities, and/or a respiratory measurement called forced vital capacity.

The trial took place at California Pacific Medical Center in San Francisco, the University of Kansas Medical Center in Kansas City, and Johns Hopkins University in Baltimore. All three institutions are sites for MDA/ALS Centers, from which study participants were drawn (although MDA did not directly support this study).

Jeffrey Rothstein, who directs the MDA/ALS Center at Johns Hopkins University in Baltimore, said the ability to maintain muscle strength or delay its deterioration could have a significant impact on quality of life for people with ALS.

SB509 trial participation

The moderately positive findings for SB509 may mean that it will move into phase 3 (large-scale) testing. MDA will announce details about study recruitment, when and if they become available, on its Web site and in its MDA ALS Newsmagazine.

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