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Alnylam Pushes Back Pediatric Trial of RSV Drug to Wait for Adult-Trial Data

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Alnylam Pharmaceuticals has pushed back by at least six months the expected start of a phase II study of its respiratory syncytial virus treatment ALN-RSV01 in young children in order to wait for data from a separate trial of the drug in adult patients, company officials said last week.
 
Earlier this year, Alnylam began a phase II study of ALN-RSV01 in adult lung transplant patients naturally infected with RSV (see RNAi News, 4/10/2008), but had been planning to start evaluating the drug in a pediatric population — the drug’s primary market — before year end.
 
Last week, however, Alnylam management said during the company’s third-quarter financials conference call that the pediatric trial would not begin until after the study in lung-transplant patients concludes around the middle of next year.
 
“Our goal is to move forward in [a pediatric] population with the right levels of both prudence and urgency — prudence, as this is a pediatric population where we want to proceed wisely, and urgency, as there is a very high level of unmet need for therapeutic approaches for these patients,” Akshay Vaishnaw, Alnylam’s vice president of clinical research, said during the call.
 
Based on internal discussions and talks with the US Food and Drug Administration, “we believe that the results of our current lung-transplant phase II trial will be important and informative prior to initiating our pediatric phase II study,” he noted. “Therefore, our current plans are to initiate the pediatric phase II trial upon completion of the ongoing adult phase II study.”
 
Vaishnaw added that enrollment in the phase II RSV study in adults is expected to conclude in mid-2009, with data available “soon thereafter.”
 
Alnylam CEO John Maraganore stressed that the delay only impacts the timing of the pediatric trial and would not change the company’s as-of-yet undisclosed projected commercialization date for ALN-RSV01.
 
“There is no change in our overall perspective on how we advance this program through the market and the timing of that,” he said. “We’re just changing some of the staging and some of the strategy around” the drug’s development.
 
“We obviously had a different … plan earlier in the year,” he added, “but we want to be able to do the right thing … [which is to] complete the lung transplant study and to advance from there.”
 
Maraganore added that the change in timing of the pediatric trial might speed up ALN-RSV01’s overall development.
 
“We think we are going to learn something from the adult study that will be very helpful for how we advance and how rapidly we advance with a pediatric study,” he said. “Drug development … is greatly accelerated when you have additional data that allows you to more rapidly accrue patients … [and the lung transplant data] will help in terms of the rates of accrual in the pediatric study.”
 
About-Face
 
Also during the conference call, Maraganore confirmed that Alnylam would be using the SNALP drug-delivery technology of partner Tekmira Pharmaceuticals with its liver cancer program, rather than the so-called lipidoid technology licensed from the Massachusetts Institute of Technology (see RNAi News, 5/10/2007).
 
The move is an apparent about-face for the company based on earlier comments by David Bumcrot, Alnylam’s director of research, who told attendees of the Beyond Genome conference in mid-2007 that the company would use the MIT technology with both its liver cancer and hypercholesterolemia programs (see RNAi News, 6/28/2007).
 

“Our goal is to move forward in [a pediatric] population with the right levels of both prudence and urgency — prudence, as this is a pediatric population where we want to proceed wisely, and urgency, as there is a very high level of unmet need for therapeutic approaches for these patients.”

The SNALP, or stable nucleic acid lipid particle, technology has been an important part of Alnylam’s research efforts over the past few years. Notably, Alnylam and Protiva Biotherapeutics — which merged with Tekmira earlier this year (see RNAi News, 4/3/2008) published data in 2006 showing that SNALPs could be used to deliver siRNAs against another cholesterol target, apolipoprotein B, in non-human primates (see RNAi News, 3/30/2006).
  
But last year, Bumcrot said that Alnylam had chosen to use the lipidoid technology in the liver cancer and hypercholesterolemia programs in part because of its ability to effectively enter liver tissue.
 
About a year later, however, Alnylam began to backtrack when it said in a press release announcing its second-quarter financials that data on the liver cancer drug, called ALN-VSP, “were generated in collaboration with Tekmira using their … SNALP technology.”
 
At the time, an Alnylam spokeswoman told RNAi News via e-mail that the drug “comprises small interfering RNA molecules delivered systemically using Tekmira’s SNALP technology,” but declined to elaborate.
 
In response to an analyst’s question during the conference call, however, Maraganore left no doubt as to what delivery technology will be used in the liver cancer program, stating that the company had “locked down” its decision to use the SNALP technology.
A call to Alnylam requesting additional comment on the decision was not returned.
 
A phase I study of ALN-VSP in patients with either primary or secondary liver cancer is expected to start in the first half of 2009.
 
The Financials
 
For the third quarter, Alnylam posted a sharp drop in its net loss to $2.9 million, or $0.07 per share, from a year-ago loss of $52.8 million, or $1.35 per share.
 
Helping drive down Alnylam’s losses was a decrease in research and development expenses to $22.1 million in the third quarter from $59.6 million in the same period a year earlier. The company attributed the lower R&D spending to fees paid to third parties including Isis Pharmaceuticals in connection with Alnylam’s alliance with Roche (see RNAi News, 7/12/2007).
 
Revenues, meanwhile, jumped to $25.7 million from $16.3 million in the third quarter of 2007, primarily due to $13.7 million in net collaboration revenues Alnylam received in connection with its Roche deal and $5.4 million received from partner Takeda Pharmaceutical (see RNAi News, 5/29/2008).
 
As of Sept. 30, Alnylam had cash, cash equivalents, and marketable securities totaling $520.2 million, excluding a $20 million technology-transfer milestone achieved under the company’s arrangement with Takeda. That payment will be recorded in the fourth quarter of this year, Alnylam said.
 
Looking ahead, Alnylam said its balance of cash, cash equivalents, and marketable securities will be greater than $500 million by the end of 2008, exceeding previous guidance of around $500 million.
 
“This very strong cash position, combined with our expectation for continued funding from current and future alliances, allows us to invest fully in the advancement of our platform and RNAi therapeutic programs with no need to raise new capital in the equity markets for the foreseeable future,” Patricia Allen, vice president of finance and treasurer at Alnylam, said in a statement.

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