It’s not unusual for me to get comments about my posts – some supportive, some telling me that I am pretty dumb. However, it is rare to get comments back from one of the principals of a post. Last week, I wrote about the decision of Novartis to exit research in the area of RNA interference (RNAi) and took the view that, while RNAi has its place among future therapies, it was not nearly as promising as it once was. After the post appeared, I quickly heard from Dr. John Maraganore, the CEO of one of the world’s leading RNAi companies, Alnylam. Worried that this might be a cringe inducing phone call, I was prepared for the worst. Actually, our discussion proved to be fruitful.
Maraganore made a number of points. First of all, he believes that RNAi can be successful in areas where monoclonal antibody drugs (mAbs) come up short. He used Alnylam’s work on transthyretin-mediated amyloidosis (ATTR) as an example. ATTR is a progressive, debilitating disease that is often fatal. It afflicts roughly 50,000 people worldwide. The key to treating this disease is blocking plasma transthyretin (TTR), thereby blocking amyloid deposition in the liver. However, plasma levels of TTR are so high in ATTR patients that targeting this with a mAb would be difficult. Alnylam’s RNAi technology enables direct blocking of TTR synthesis in the liver. Monoclonal antibodies can’t do this.
Maraganore also believes that that RNAi technology can provide valuable alternatives to mAb therapy. Alnylam has a program that is going after Alexion’s Soliris, the world’s most expensive drug at $440,000 per year per patient. Soliris patients require frequent IV infusions, but Maraganore maintained that “We are effective with weekly sub-cutaneous injections and we can also be less expensive.” Payers would certainly welcome a less expensive alternative to Soliris.
The hottest area in cardiovascular research is in PCSK-9 inhibitors, potent LDL cholesterol lowering drugs. Alnylam is working hard on this target as well. Maraganore believes that an RNAi, which blocks the synthesis of PCSK-9, will be more effective in lowering LDL cholesterol than the
Maraganore admits that RNAi drugs will be limited to diseases where delivery of the drug as well as the costs of making these materials will be acceptable. “Yes, it’s a specialized technology. But it doesn’t have to cure cancer to be of value.” Fair point.
The day after Novartis announced that it was dropping its RNAi research, Alnylam COO, Barry Greene, made news by saying that: “Novartis pulling out is an exemplar of Big Pharma not being able to innovate, and historically they have never been able to innovate.” This is a pretty provocative comment and certainly not something that I personally agree with. I asked Maraganore if he supported his COO’s position.
“I think that Barry’s comments really reflect our view that it’s been very tough for large companies to innovate around earlier stage technology platforms. This was true in the 80s with rDNA and the 90s with mAbs. Biotechs were needed to tackle the obstacles. We think the same applies for RNAi. Our view is that Pharma decisions on technology platforms are hardly a barometer of the platform’s ultimate success for R&D.”
Well, we will all get a chance to watch this evolve over the coming years, particularly as Alnylam plans to go head-to-head with current technologies. If it is successful, it will be lauded by patients and physicians for new treatments, and by payers and healthcare systems for lowering the high cost of treating certain diseases.
