NEW YORK (GenomeWeb) – Alnylam Pharmaceuticals this week released data from an ongoing Phase II open-label extension study of its TTR-mediated amyloidosis therapy patisiran, which showed that the drug treatment was associated with a stabilization of neurological impairment progression in patients with a form of the disease called familial amyloidotic polyneuropathy (FAP) after six months.
Investors responded positively to the news, sending shares of Alnylam up more than 20 percent in mid-Monday trading on the Nasdaq to $89.07.
Still, Alnylam officials have been careful not to give too much weight to the data given that the trial is open label, uncontrolled, and involves only 27 patients. A Phase III study testing patisiran in up to 200 individuals with FAP began early this year.
ATTR is a condition characterized by the accumulation of amyloid deposits in tissues such as peripheral nerves and the heart. FAP typically affects the peripheral nervous system, while a manifestation of the disease called familial amyloidotic cardiomyopathy, which Alnylam aims to treat with a subcutaneously delivered form of patisiran in Phase II testing called ALN-TTRsc, primarily impacts heart tissue.
Both drugs are designed to silence the mutant form of the TTR gene, which causes the disease, as well as the wild-type form, but each uses a different delivery technology.
In late 2013, Alnylam kicked off the open-label extension study of patisiran, rolling over essentially all patients from its completed Phase II trial that showed the drug could suppress TTR levels by as much as 93 percent with multiple intravenous doses of up to .3 mg/kg.
The extension study is designed to provide information on the long-term safety and tolerability of patisiran at doses of .3 mg/kg once every three weeks, in addition to measuring its effects on various clinical endpoints including a modified neuropathy impairment clinical scoring system known as mNIS+7 that evaluates muscle weakness, sensory and autonomic function, and nerve conductance. Notably, mNIS+7 measurement is the primary endpoint of the Phase III trial, which is also using the Phase II dosing regimen.
At the American Neurological Association annual meeting this week, Alnylam presented six-month data on 19 patients in that trial, which showed a mean .95 point decrease in mNIS+7 scores.
This decrease in neuropathy progression, the company said, compares favorably to the seven to 10 point increase in mNIS+7 that has been observed in historical datasets in untreated FAP patients, including ones in a natural history of disease study conducted by the company.
Further, the data show that patisiran led to a sustained mean serum TTR knockdown of 80 percent for over nine months, with an up to 89.6 percent knockdown reached between doses. There have been no adverse events associated with treatment and all 27 patients in the open-label study continue to receive treatment, Alnylam said.
Speaking during a conference call held to discuss the open-label trial results, Alnylam CMO Akshay Vaishnaw said that the data, taken together, indicate that "we're achieving disease stabilization with administration of patisiran in FAP. … It should be noted that this is what we believe to be the industry's best evidence to date that RNAi can be achieved in humans over a long duration of treatment."
However, he stressed that the newly presented data are from a single-arm, open-label, uncontrolled study in a small number of patients. "Accordingly, it will be interesting to see how these results look at 12 and 18 months and beyond," Vaishnaw said.
Also cautioning about the importance of the Phase II data was Alnylam Chief Business Officer Laurence Reid, who discussed the released of the data earlier this month at the Leerink Partners Rare Disease Roundtable. Pointing to the small patient group and uncontrolled nature of the extension study, he said that "for scientific reasons, that no overt deductions … can reasonably be made from the data.
"From a clinical perspective, the sustained knockdown of TTR that we'll be showing … will speak for itself," Reid added. "But in terms of clinical efficacy, it is too early for us to make any definitive deductions, which is frustrating for all concerned but it is what it is, and it's the clinical and statistically reality … of the study."