Alnylam Pharmaceuticals this week provided an update on its flagship TTR-mediated amyloidosis drug ALN-TTR02, stating that it has begun enrollment in an open-label extension study of a recently completed phase II trial and unveiling the compound's international nonproprietary name — patisiran.
A phase III trial of the agent remains on track to begin before the end of this year, alongside a subcutaneous version that is poised to advance into phase II, the company said during an announcement of its third quarter financial results.
Meanwhile, Alnylam continues to transfer RNAi technology and patents to ag-bio giant Monsanto as part of a licensing deal the companies inked last year, with a final $1 million milestone payment due upon the completion of these activities.
ATTR is caused by mutations in the TTR gene, which triggers accumulation of abnormal amyloid proteins in the body. Patisiran comprises siRNAs designed to inhibit both the wild-type and mutant forms of the protein.
This summer, Alnylam released positive interim data from a phase II trial of the drug, which showed that it could suppress levels of its target by as much as 93 percent in patients (GSN 7/3/2013). Specifically, multiple 0.15 mg/kg and 0.30 mg/kg doses of patisiran led to rapid, dose-dependent, and durable knockdown of serum TTR levels, with the highest dose achieving the greatest effects.
Last month, Alnylam completed enrollment in that study, and complete results are scheduled for presentation at the International Symposium on Familial Amyloidotic Polyneuropathy next week.
Notably, the company has also begun enrolling patients from the phase II trial in an extension study where they will be able to receive 0.3 mg/kg doses of the drug every three weeks for an additional two years, Alnylam CMO Akshay Vaishnaw said during a conference call held to discuss the third quarter results.
"This study will evaluate the long-term safety and tolerability of patisiran and will also measure effects of treatment toward a number of clinical endpoints, including a modified neuropathy impairment" clinical scoring system, he said. "We plan to report clinical data from this study about once a year with initial data in 2014."
Alnylam CEO John Maraganore added that the company anticipates that "the majority of patients" treated in the phase II will "rollover" into the extension trial.
"It’s one of the benefits of going into the phase II study, knowing that ultimately they can get access to [the] drug for the foreseeable future," he said.
Given the positive advances in phase II, Vaishnaw confirmed that Alnylam is on schedule to begin this year a phase III trial — its very first — with patisiran in patients with a manifestation of ATTR called familial amyloidotic polyneuropathy.
The study's primary endpoint will be the difference in change from baseline as measured by the modified neuropathy impairment scoring system after 18 months in patients receiving patisirin and those receiving placebo, he said.
Importantly, Alnylam has already obtained protocol assistance for the planned pivotal trial from European regulators and has completed its end-of-phase II meeting with the US Food and Drug Administration, Vaishnaw added.
As part of a larger effort to end its reliance on the lipid nanoparticle technology used in patisiran, which was licensed from Tekmira Pharmaceuticals prior to a divisive lawsuit between the firms, Alnylam continues to make progress with a subcutaneous version of the ATTR drug called ALN-TTRsc.
The drug uses Alnylam's proprietary GalNAc technology, which facilitates liver delivery of siRNAs via uptake through the asialoglycoprotein receptors expressed on the surface of hepatocytes. In July, the company reported top-line data from an ongoing phase I study of ALN-TTRsc, showing that the drug could knock down serum levels of its target protein by more than 80 percent (GSN 7/11/2013).
Vaishnaw said that Alnylam anticipates starting a pilot phase II trial of ALN-TTRsc in ATTR patients with a form of the disease called familial amyloidotic cardiomyopathy by the end of 2013, with results ready for public release in 2014.
In an effort to generate revenues from its core technology in areas outside of its human therapeutic focus, in late 2012 Alnylam signed an agreement giving Monsanto the exclusive, worldwide rights to its portfolio of RNAi know-how and intellectual property for $29.2 million (GSN 9/6/2012).
Alnylam was also eligible to receive $5 million in milestones based on the completion of technology transfer and patent-related activities, and in December 2012 received $1.5 million of that total.
In August, Alnylam received an additional $2.5 million for completing the technology-transfer work, it disclosed in a filing with the US Securities and Exchange Commission this week.
Alnylam stands to receive a final $1 million payment, as well as single-digit royalties on product sales and a cut of sublicense fees Monsanto receives for providing access to the RNAi technology to other companies.
For the three-month period ended Sept. 30, Alnylam's net loss jumped to $29.7 million, or $0.48 a share, from $19.5 million, or $0.38 a share, the year before.
Revenues in the quarter fell to $9 million from $16.8 million in the same period a year earlier, while research and development spending climbed to $34.5 million from $22.1 million. General and administrative spending, meantime, fell to $6.8 million from $12.8 million.
At the end of the third quarter, Alnylam had cash, cash equivalents, and marketable securities totaling $367.1 million. The company said it expects to end 2013 with more than $320 million.