BOSTON—We caught up with BIO board chair and Alnylam CEO John Maraganore at this year's meeting and asked him about a range of topics, from preserving innovation and urgency as a biotech company grows to Alnylam's pricing plan for its gene-silencing therapies to how he felt when tweeting at President Donald Trump that he was "proud to be a 'shitholer.'"
Responses have been edited for length and clarity.
FierceBiotech: The last time we caught up with you was at J.P. Morgan, where [Alnylam president] Barry Greene outlined your transition from R&D mode to a commercial-stage biotech. Aside from the obvious—the upcoming approval and launch of patisiran—what's on the horizon for Alnylam?
John Maraganore: We have three other programs that are in phase 3 with two more to follow by the end of the year. For our porphyria program, the readout of the interim analysis that will be done in support of accelerated approval will, if positive, lead to an NDA filing by the end of the year, with a U.S. launch in 2019. Our primary hyperoxaluria program (lumasiran) will go into phase 3 in the middle of this year and we expect that to lead to approval in 2020. Finally, our TTR-sc02 program will go into phase 3 this year and we expect a 2021 approval.
Our plan has us launching in 2018, '19, '20 and '21, with two other programs in phase 3 that are led by partners. Sanofi is leading our fitusiran program in hemophilia and The Medicines Company is leading our inclisiran program in hypercholesterolemia. The data readouts for those should be in the 2019/2020 timeframe, with approvals in 2020 and 2021. So we're set up for some pretty explosive opportunities that will be coming to market in the next period.
FierceBiotech: A recurring topic in the industry is the culture at small biotechs versus Big Pharma. To quote Barry, "Companies don't get sold. They get bought. Novel technology is better off in the hands of hungry biotech people who live and die to make it work." What would you say to people who point to Alnylam and say, "hey, actually, they're not really that small anymore, can they really keep up the innovative pace of a biotech?"
John Maraganore: There's no doubt that as we grow, one of the challenges will be keeping the culture; keeping the urgency the same, keeping the passion the same. Part of the wonderful thing we have in front of us the fact that we are building this company from scratch.
A lot of companies that are larger, more bureaucratic and slow have gotten that way over decades. And they got that way through multiple different leaders over time. We've had the same leadership team—not just me, but Barry, Akshay [Vaishnaw], the head of R&D, and now others we've added to the team—but we've been together for over a dozen years. That allows us to think about how we grow and scale and maintain the core cultural elements that have allowed us to get here.
The other thing that's happened at companies that have not done it as well, in my opinion, is that they've built their company through M&A, as opposed to doing it organically. When you put pieces of companies together like a puzzle, you struggle. You’ve got one culture over here that you're trying to link up to this culture over here. That’s something we've not done.
FierceBiotech: Alnylam has been discussing pricing and value-based pricing for patisiran for a while. What have you heard from payers so far?
John Maraganore: I've never been privileged enough to be involved in a drug as transformative as patisiran. But we also have a disease associated with an enormous economic burden as well as an enormous disease burden—it's progressive, debilitating, fatal. With orphan diseases, we think about the economic burden not only for patients, but for caregivers as well and the value of the medicine in that context. How are you impacting economics of that patient's care by virtue of having this medicine even though that patient's cost is an expensive drug at the end of the day? We have to factor all that into our thinking about pricing.
In all our discussions with payers, we are talking proactively about value-based payments. We will put our money where our mouth is and expect to get reimbursed at a specific price if the drug does what it's supposed to do. If the drug doesn't perform as well as we expect it to perform, then we would get reimbursed at a lower price.
FierceBiotech: How do we think about developing drugs for rare and orphan diseases versus something like cancer that is more widely understood? How do we design trials and measure progress when creating new treatments to address areas of unmet need?
John Maraganore: I think it depends on the disease. For example, in hATTR amyloidosis, we have data that says we're actually stopping or even improving neuropathy progression in the majority of patients. We also know that after three to four doses, patients are no longer losing weight and are either maintaining or gaining weight at the time.
The ability of actually stabilizing or gaining weight is an early readout of the drug's activity that is clearly impactful for the patient. But when we communicate it to the community more broadly, we don't talk about that per se, we talk about the impact on neuropathy and how these patients are no longer going through the process of losing their ability to walk. We've had patients on the study who went from needing a cane to walk to being able to walk without assistance. Those types of examples are powerful in the end.
FierceBiotech: What went through your mind when you saw that President Trump had asked at a White House meeting why he should accept immigrants from “shithole countries” rather than from places like Norway?
John Maraganore: I'm still proud to be a shitholer. I'm the fortunate son of two Greek immigrants who came to this country with very little, because they believed in opportunity, believed in building something. We're all immigrants in this country—unless you're an American Indian, you are an immigrant in this country. And the assault on immigration and the assault on diversity and people of different races or from different countries is just unacceptable in my mind.
As a biotech company, we're developing medicines for global diseases that affect every type of individual regardless of gender, race, sexual orientation. It doesn't matter. So how can we possibly be involved in developing medicines for everyone if we're going to be exclusionary in any way, shape or form?
I think leaders need to stand up and say something. We can't be quiet. If we're quiet, we're allowing it to happen.