But the length of that investment – the time it would take to understand the best targets and develop the most effective delivery strategies – may have been more than the companies that dropped RNAi could bear. Though Krieg and his colleagues at Pfizer hoped to get an RNAi compound into the pipeline by this year and were making progress with their top candidate, a treatment for liver cancer, the team still had some distance to go by the time their program folded.
Krieg suspects that the story at Pfizer is the same elsewhere. As the company started to realize how much of an outlay RNAi would take to get to the clinic, it realized it probably wouldn’t be able to recoup its investment. “The lifetime of patents by the time you get a drug approved is really insufficient to return the investment on a drug most of the time,” he explains. “If you look at the pipeline, it’s inadequate to support their infrastructure.”
Roche, which also has invested heavily in RNAi therapeutics during the past few years, pouring hundreds of millions into its collaborations with biotech partners, issued a cagey statement about its own decision to leave RNAi behind. “The primary goal is to enable this important scientific work to continue outside of Roche and offer the best chance of success in providing benefits to patients,” it said, adding that “Roche would consider the possibility of re-entering the field through external collaboration as clinical stage compounds emerge.”
That re-entry might be just around the corner, says Barry Greene of Alnylam Pharmaceuticals, an RNAi therapeutics company that partnered with Roche until the company severed its agreement with Alnylam late last year.
Greene points out that Alnylam and other companies are rapidly moving ahead with their own RNAi therapeutics. At his company alone, several RNAi-based drugs already are moving through clinical trials. Alnylam even started its own initiative earlier this year named “Alnylam 5 x 15”—an effort to get five products in advanced clinical development by the year 2015. The most advanced therapeutic candidate in this program is a drug for transthyretin amyloidosis, an autosomal inherited disease that affects about 50,000 people worldwide and universally kills patients within five to 15 years of diagnosis. The drug currently is in Phase 2 clinical trials.
This disease, which attacks the liver, is an attractive target since the organ has a natural propensity to take up the nanolipid delivery vehicles created by Alnylam partner Tekmira that encapsulate the desired RNAi snippets.
Greene notes that Alnylam also has other RNAi-based drugs in clinical trials with the aid of pharmaceutical partners, including one for respiratory syncytial virus in Phase 2 and one for liver cancer in Phase 1. He hints that Roche and other companies soon will rue the day they decided to back out of RNAi research.
“I used to run the Boston Marathon every year, and this is like someone signing up and then quitting about 12 to 13 miles into the race,” he says. Those companies that gave up too early, he adds, “aren’t prepared to feel the thrill of the finish line.”