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Biogen Idec announces favorable Phase III data on dexpramipexole. ALS is a complex disease that is probably caused by multiple factors, and the various drug candidates work through different mechanisms, he says. Just as in multiple sclerosis, there could be a market for a number of new drugs for ALS, Perrin says.
“I would imagine that one drug isn’t going to solve all of it,’’ Perrin says.
Perrin’s institute is helping Novartis in studies of an ALS drug candidate, fingolimod (Gilenya), and he anticipates data on that drug in mid-2013. The drug is already approved to treat multiple sclerosis. The compound works by curbing the activities of immune system cells that can cause nerve damage, according to PubMed Health. Fingolimod, an oral capsule, may substantially slow the heartbeat, so patients take it in a medical facility where they can be observed for at least six hours.
Cytokinetics is pinning its hopes on observations from two Phase II trials whose main purpose was to establish safe dosing procedures for tirasemtiv. But the results, reported in April, also suggested that tirasemtiv might slow the decline of physical functioning and preserve the capacity to breathe. An analysis of the trial results also hinted that at the higher doses tested, 250 mg and 375 mg daily, some subjects might get a bit better than they were before treatment began.
If that pattern proves to be statistically significant in the ongoing Phase IIb trial in 400 subjects, Cytokinetics may seek FDA approval based solely on that new data, Blum says.
“If at the end of three months, patients are doing better than their baseline, we think that would make a compelling case for single study approval,” Blum says.
ALS patients usually decline at a rate of about 0.92 points per month on a 48-point scale used in an evaluation tool called the ALSFRS-R, or ALS Functional Rating Scale, revised form. The scale assesses changes in 12 major areas of activity, including ease of walking and speaking. After three months without treatment, a typical patient’s score would decline by 2.7 points, Blum says. Cytokinetics is hoping to reduce that number.
In the Phase IIb trial, the tirasemtiv dose will be gradually elevated to 500 mg a day for subjects who are not in the control group given a placebo. The daily amount of tirasemtiv will be split into two doses of 250 mg to minimize the dizziness some trial subjects have experienced in their first week taking the drug, Blum says.
Cytokinetics, which finished the third quarter with $81.2 million in cash and cash equivalents, can fund the $30 million Phase 11b trial itself, according to the public company’s statements. In June, Cytokinetics raised $60 million through sales of common stock, convertible shares and warrants.
But the South San Francisco company, founded in 1997, is looking for a partner for tirasemtiv and its entire program in skeletal muscle activation. That drug mechanism could prove useful in maladies in addition to ALS, such as the muscle weakening that comes with aging, AIDS, cancer, and muscular dystrophy, Blum says.
Cytokinetics’ share price dropped below the Nasdaq exchange’s minimum of $1 this year, triggering a June warning that the stock might be delisted if the price doesn’t come back into compliance by Dec. 17.
Neuraltus, a private company that began operations in 2009, intends to begin a Phase III trial of its ALS drug candidate by the second half of 2013. But it must find a partner, says CEO John Walker.
Neuraltus sees promise in its investigational drug NP001 based on the results of a Phase II trial in 136 subjects with ALS. A study analysis released Oct. 29 showed signs that the compound might slow or even halt the progression of ALS. That intriguing trend did not meet the standard of statistical significance, says Dr. Gil Block, chief medical officer of Neuraltus.
But a post-hoc analysis that included historical control data, and meetings with the FDA, encouraged the company to plan for a Phase III trial.
After six months of treatment with 2 mg of NP001 per kilogram of body weight, 27 percent of subjects either improved or did not decline on the ALSFRS-R scale, the post-hoc analysis of the Phase II trial indicated. By comparison, no decline was seen in 19 percent of subjects who received 1 mg of NP001 per kilogram, and in 11 percent of subjects receiving a placebo, Block said. NP001 is a small molecule given intravenously.
Walker says Neuraltus has recently started discussions with potential partners. The CEO says a partner willing to invest in the NP001 program could find out within six months whether the drug’s promising pattern will hold up and produce a marketable product. If the data were very strong, he says, the single Phase III trial might form the basis for a New Drug Application to the FDA by the end of 2015.
NP001 is designed to stop a cascade of damage to neurons caused when immune system cells called macrophages shift from their normal role and begin releasing toxic compounds. Block says the drug, which can moderate the body’s inflammatory response, has potential in disorders in addition to ALS.
Perrin says the increased research activity in ALS seems likely to turn up some new answers.