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on measurements of effectiveness. The main measurement of disease progression in ALS patients is something called the ALS Functional Rating Scale (ALSFRS-R), Shefner says. It’s a composite score researchers compile based on a questionnaire to patients, in which they are asked about their ability to do basic daily activities like walking, climbing stairs, speaking, swallowing, getting dressed, and brushing teeth. Patients with ALS are generally expected to decline each month, losing about 0.9 points on the ALSFRS score, says Cytokinetics CEO Robert Blum.
In this trial, researchers assessed ALSFRS scores at two points—Days 8 and 15. When data from those snapshots were combined, researchers saw an average decline of 0.5 points in the placebo group—about what would normally be expected. Those on the low dose of the Cytokinetics drug didn’t do much better, seeing an average decline of 0.3 points on their ALSFRS scores. But those on the medium and high doses did better, seeing a 0.4 point gain and a 0.6 point gain on the medium and high doses, respectively, after 15 days, researchers said. There was a 90 percent chance that the finding was due to the drug, not a result of random chance, scientists said. While that is fairly close to being a statistically valid finding, it’s not enough, because the FDA standard for statistical significance is that clinical trials need to be 95 percent certain that a drug is causing the desired effect.
Still, in a disease like ALS where there has been so little progress, this is encouraging news, Shefner says. Cytokinetics is now working on crafting a plan for a more rigorous, Phase III clinical trial that will be designed to show whether its drug is truly effective or not. The company is in conversations with regulators in the U.S. and Europe about what such a study will look like, so details aren’t yet available, but Blum says it will enroll “hundreds, not thousands” of patients, who will be dosed for a minimum of three to six months. The main goal will likely be to see how the drug affects ASLFRS scores, which Shefner said is the goal that’s most accepted within the field. A study could be designed to gather supplementary data on how well patients breathe, how strong they remain, and whether they can stay off ventilators for a longer period of time. Cytokinetics’ goal will be to start the final phase trial program before the end of 2012, Blum says.
“What we’ve seen has been consistent from preclinical tests, to tests in healthy subjects, and in ALS patients,” Blum says. “This drug is ruthlessly consistent.”
Cytokinetics isn’t the only company working hard on new treatments for ALS. Weston, MA-based Biogen Idec (NASDAQ: BIIB) is already in the third and final phase of clinical trials with a drug called dexpramipexole that is designed to work through a different biological pathway. That product is being evaluated based on a composite goal that combines the ALSFRS scores and survival times. Shefner, who has collaborated with Biogen on testing that drug as well as the one from Cytokinetics, said he’s optimistic about that program because it has already shown encouraging preliminary results after evaluating patients for three months. Ultimately, he said he’s hopeful that both will work and that they might eventually be used in combination.
That’s still an idea that’s a ways off. But Shefner kept coming back to the idea of how “unique” it is to see ALS patients improving after two weeks on therapy. He’s clearly itching to find out if that effect can be sustained over a period of several months, on an FDA-validated score. “It’s quite tantalizing,” Shefner says.
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