Neurotrope nosedives on iffy Alzheimer's trial
- Neurotrope BioScience has trumpeted some modestly positive topline Phase 2 results for bryostatin-1 in the tough-to-treat moderate to severe Alzheimer's disease population. The stock price tanked by almost 63%, falling from $18.81 to $6.97 at close of play on Monday, tweaking up to $7.03 after hours.
- While there was a high dropout rate in the study, those in the lower dose group showed a slightly positive impact. This group showed a 1.5 point improvement in the Severe Impairment Battery (SIB) cognition measure, compared with a fall of 1.1 in the placebo group (p<0.07). Results were not statistically significant and the Food and Drug Administration typically wants to see a greater improvement than seen here.
- Unlike many of the other failed Alzheimer's drugs that the industry has tried over the years, bryostatin-1 does not work by affecting beta-amyloid plaques or tau, but instead hopes to prevent the loss of neurons in the brain.
While Neurotrope BioScience did its best to spin good results out of bad, the investors just aren't buying it. Literally. The stock price fell by almost two thirds on the mildly positive outcomes in a small study with almost a third drop-out rate.
"This is only one of a handful of studies that has shown a positive result in past years. The signal may not yet be fully optimized," said Susanne Wilke, Neurotrope's CEO, somewhat hopefully, on the company's conference call.
One of bryostatin-1's unique upsides, according to the company, is its potential to regrow synapses and reverse disease: "We saw improvement in the Severe Impairment Battery cognition measure, not just a delay in worsening the disease. Putting the results in a clinical context, the improvement of 1.5 in the treated group was against a decline in 1.1 in the placebo group, so effectively almost a 3 point increase."
Yet, it was not a three point increase; the increase was only 2.6 points, whereas the FDA usually requires an improvement of three to four net points. The results were also not statistically significant.
The team at Neurotrope are remaining almost relentlessly upbeat. They will continue to analyze other data from the study, including the length of the effect after cessation of dosing, and Daniel Alkon, president and CSO, also reiterated on the call that the study was only Phase 2 and designed to look at safety and dose ranges, not efficacy.
"The study wasn't powered to have a Phase 3 conclusion, and we met our pre-specified p values of less than 0.1," said Alkon. "Deeper analysis is under way, and further investigation is warranted, for example we have seen indications of widening of benefit 30 days after the last dose at 20 mcg, and saw some efficacy from the 40 mcg dose at the beginning, but this then lost its effect. It may be that it retains its efficacy in less frequent doses. We will release more detail in a couple of months. Stay tuned – there is much more to come."
The company plans to meet with the Food and Drug Administration to discuss the possibility of an open label study with all the patients who have taken the drug or placebo so far, giving them the optimized doses for a prolonged period. The company also plans a dose-ranging study over around 8 weeks, including different patterns of dosing, and a pediatric trial in Fragile X syndrome, and is very keen to seek out corporate partners for further work with bryostatin-1.
"Many companies are focused on approaches based on amyloid plaque or tau tangles, and are looking for new mechanisms of action. Bryostatin-1 works through synaptic growth factors as well as anti-amyloid and anti-tangle signaling pathways," says Wilke.
Neurotrope isn't the only company to stumble over Alzheimer's disease clinical trial failure. These have been hitting both the great and the small, from Eli Lilly & Co., to Johnson & Johnson, Elan and Pfizer. It will be interesting to see if Neurotrope's enthusiasm is realistic, but the problem with developing Alzheimer's disease drugs is that it takes a lot of money and time to find out.
- Neurotrope BioSciences Statement
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