Alnylam, Studying History of Genzyme, Eyes Drug to Make Big Impact for Rare Disease

12/14/09Follow @xconomy

Alnylam Pharmaceuticals has a technology, RNA interference, that scientists say has potential to break new ground against hundreds of diseases for decades to come. But when you have a proverbial “platform” technology that can do so much, how exactly should you set priorities, and decide which drugs to develop first?

I got a sense for how Alnylam CEO John Maraganore thinks about this a few weeks ago when I visited his office in Cambridge, MA, and asked about a treatment his company is developing for something called TTR amyloidosis. I’m sure he’ll have more to say about this when he appears today at an Xconomy event on life sciences innovation in San Diego.

Alnylam (NASDAQ: ALNY) has made waves the past few years as the leading company developing RNA interference drugs, which have the potential to specifically silence disease-related genes that have been inaccessible to drugs of the past. Alnylam has chosen to remain small, with just 180 employees, while pursuing many opportunities through its network of partnerships with big drugmakers like Roche, Novartis, GlaxoSmithKline, and others. The partnerships are critical, because they provided early validation for Alnylam’s technology, along with more than $600 million in cash, and helped it build a stock market valuation of more than $680 million. That’s all helped Alnylam advance two RNAi treatments into clinical trials, one for respiratory syncytial virus and another for liver cancer.

But the third drug in Alnylam’s pipeline, ALN-TTR, reveals another kind of strategy at work at Alnylam, one that looks a lot like the trail blazed twenty years ago by Cambridge, MA-based Genzyme. This is the model that says it’s better to retain 100 percent of the commercial rights to drugs that can make a big difference for a small number of patients with a severe genetic disease, and command premium prices for those drugs.  ALN-TTR is one drug Alnylam wants to keep to itself, at least in the world’s top two pharmaceutical markets, the U.S. and Europe.

Alnylam CEO John Maraganore

Alnylam CEO John Maraganore

“This is an area we can build our company around,” Maraganore says.

The disease, transthyretin (TTR) amyloidosis, appears in patients with a mutation of a gene, concentrated in the liver, that allows excessive amounts of amyloid proteins to build up in the body. People are born with the condition, but usually don’t see symptoms until their 30s or 40s. Once symptoms appear, people suffer progressive damage to the nerves and the heart. The only treatment is a liver transplant. People usually die about nine to 11 years after symptoms appear, Alnylam has said.

About 10,000 people worldwide have the nerve-damaging form of the disease (familial amyloidotic polyneuropathy) and an estimated 40,000 worldwide have the heart-damaging effect (familial amyloidotic cardiomyopathy). That’s a small population in the global scheme of things, but Maraganore notes that only about 10,000 people worldwide have Gaucher’s disease, and that still became the basis for a billion-dollar annual market for Genzyme’s imiglucerase (Cerezyme).

But why does TTR amyloidosis make an attractive target from a science standpoint? Maraganore zipped through the logic. The disease symptoms are clearly linked to the gene mutation, without a lot of other complicating factors. The company’s small interfering RNA drugs can block all 100 known mutated forms of the TTR gene. Evidence is mounting that the Alnylam drug can reduce TTR protein levels in the blood by more than 80 percent in mice and non-human primates, and the effect lasts more than three weeks after a single shot. The protein is produced in the liver, and that’s one organ where Alnylam believes it can effectively deliver RNAi drugs with the help of lipid nanoparticles from its partner, Vancouver, BC-based Tekmira Pharmaceuticals.

There’s also a strong business case to make. Patients with TTR amyloidosis have a severe disease and need better treatments. The only real competition is liver transplant, although one other drug from Cambridge, MA-based FoldRx Pharmaceuticals is in clinical trials. The Alnylam treatment can be delivered in small doses, which means lower costs for raw materials for manufacturing, and therefore higher profit margins. And importantly, the clinical trial pathway is relatively quick, because researchers will be able to tell early on with objective criteria whether the drug is working.

Imporantly, the market is concentrated enough with a small number of specialty physicians that a small company can probably build a sales force large enough to commercialize such a product on its own, and keep all the profits to itself.

The plan is to begin clinical trials in the first half of 2010, Maraganore says. This puts the amyloidosis program at least a couple years behind the RSV program, which is still most likely to be Alnylam’s first marketed RNAi product, Maraganore says. But the amyloidosis treatment is “not that far behind,” Maraganore says.

Alnylam has stockpiled enough money in the bank—$453 million when it last reported financials at the end of September—that it can afford to roll the dice on clinical trials of this program on its own. That’s especially true if it continues to rack up milestone payments from partners who support its other programs. Having partners basically allows Alnylam gets to take a swing for the fence with TTR, but without betting the company’s life and death on a single drug.

“We’re excited about the potential of this. It can be a fundamental game-changer,” Maraganore says.

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  • Joan Fox

    Yes!!! We are excited about this new drug. My husband has this disease and we also had one relative die of this 20 years ago. My husband we believe may have started it with his carpal tunnel in his 40′s . Misdiagnosed almost two years ago he is now in his 4th or 5th years of symptoms. Officially diagnosed correctly l4 months ago . Have other family member with this disease. We will keep looking for more info on this. We have lost alot of time trying to find help for this disease. A daughter is negative and a son will be tested soon. Two cousins also have the mutation. I believe we heard about this process in Chicago at a Support Meeting.

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