By Doug Macron
Officials from Alnylam Pharmaceuticals this week provided an update on the company's pipeline, giving details on the timing of key programs and noting that additional patients will be enrolled in an ongoing study of its transthyretin-mediated amyloidosis treatment ALN-TTR01.
The company has also been cleared by US regulators to conduct an interim analysis of data from an ongoing phase IIb trial of the respiratory syncytial virus drug ALN-RSV01, which could prompt Alnylam to increase the number of patients in the study in order to better replicate the promising results achieved in a previous, smaller trial, they said.
The disclosures came during a conference call held to discuss Alnylam's first-quarter financial results.
TTR amyloidosis is a hereditary, systemic disease caused by a mutation in the transthyretin gene. ALN-TTR01 is a systemically delivered siRNA designed to inhibit both mutant and wild-type TTR, and entered phase I testing last summer (GSN 7/8/2010).
The study's primary objective is to determine the safety and tolerability of a single intravenous administration of the agent at doses ranging from 0.01 to 0.4 mg/kg. Secondary objectives include characterizing plasma and urine pharmacokinetics and assessing pharmacodynamic activity based on measurements of circulating TTR serum levels.
“Patient accrual in this trial is going very well,” Akshay Vaishnaw, Alnylam's senior vice president of clinical research, said during the call. “Based on the favorable safety data [available], we have received regulatory approval to extend the phase I trial with additional dose cohorts from 0.4 [mg/kg] to up to 1.0 [mg/kg], expanding the trial size from 28 to 36 patients.”
He noted that initial proof-of-concept data is expected to become available from the trial in the third quarter.
At the same time, Alnylam is moving forward with another version of the drug, ALN-TTR02, which uses a second-generation lipid nanoparticle delivery technology, and expects to file an investigational new drug application before year-end.
Also, Alnylam is preparing to analyze interim data from an ongoing phase IIb trial of ALN-RSV02 in RSV-infected lung transplant individuals, a move the US Food and Drug Administration has approved, as patient accrual in the study has gained greater momentum than expected, Vaishnaw said.
Vaishnaw stressed that Alnylam had planned to conduct the interim analysis from the very beginning, and that it does not signal any concerns the company has over how the phase IIb trial is proceeding.
Based on the outcome of the analysis, Alnylam will either keep the trial's planned enrollment of 76 patients and complete the study or increase its population to as many as 120 patients, he noted.
During the call, Alnylam CEO John Maraganore said the trial is designed to reproduce the apparent efficacy of a “relatively small” phase IIa trial. Having an interim analysis planned in such a situation “is just a wise thing.”
The analysis will be conducted when “75 percent of the patients accrued have reached the six-month primary endpoint,” expected for later in the year, Vaishnaw noted.
Elsewhere in Alnylam's in-house pipeline, the preclinical hypercholesterolemia treatment ALN-PCS, which targets proprotein convertase subtilisn/kexin type 9, remains on track to enter the clinic this year and is expected to yield human proof-of-concept data in the fourth quarter.
Additionally, an IND for the firm's recently announced refractory anemia treatment ALN-HPN, which is designed to block the iron hemeostasis-related gene hepcidin, is slated to enter human testing in 2012, while two new programs are to be unveiled later in 2011.
Alnylam's President and COO Barry Greene added during the call that the company continues to make progress in its partnered programs, including ones being led by collaborator Takeda Pharmaceutical. In March, Alnylam received a $10 million payment from the Japanese drug giant, and has now received the full $150 million in upfront fees it was owed under the companies' 2008 alliance (GSN 5/29/2008). As such, Takeda is in a position to move its RNAi programs forward, Greene said.
Takeda has publicly disclosed that it intends to file an IND on an undisclosed RNAi drug “in the 2013/2014 time frame,” Greene said, adding that since the research and development work is in Takeda's hands, he was unable to provide additional details
During the conference call, Maraganore also referenced Alnylam's ongoing legal dispute with partner Tekmira Pharmaceuticals, stating that “we were very disappointed with [its] decision to sue Alnylam.”
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In March, Tekmira filed a lawsuit charging Alnylam with misappropriating and misusing trade secrets and other confidential information related to its core lipid nanoparticle technology (GSN 3/17/2011).
At the time, Tekmira's President and CEO Mark Murray said that Alnylam had applied for patents based on Tekmira's proprietary technology and that Alnylam “stole” a new lipid delivery approach dubbed MC3.
Alnylam countersued, and charged that Tekmira had violated its agreements with Alnylam by ignoring contractual “confidential and non-public alternative dispute-resolution procedures” (GSN 4/7/2011).
This week, Maraganore said that “we believe this action is fully without merit or foundation, and in our view, it is nothing short of an unwarranted act.” He declined to elaborate.
During the first quarter, Alnylam's net loss rose 32.5 percent to $16.3 million, or $0.38 per share, from $12.3 million, or $0.29 per share, one year ago.
Revenues for the three-month period ended March 31 fell 15 percent to $20.9 million from $24.6 million in the same period a year earlier, while R&D costs climbed 7 percent to $26.3 million from $24.7 million.
The increase in R&D costs was primarily the result of higher clinical trial and manufacturing costs, Alnylam said. However, R&D spending is expected to decrease “slightly” during the rest of 2011, the company projected.
General and administrative expenses, meantime, dipped slightly to $10.2 million from $11.2 million, mainly due to lower legal costs following the settlement of a patent dispute with the Whitehead Institute for Biomedical Research, the Massachusetts Institute of Technology, and the University of Massachusetts (GSN 3/17/2011).
At the end of the quarter, Alnylam had cash, cash equivalents, and marketable securities totaling $342.8 million. The company expects to finish the year with more than $275 million.
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