It's been an eventful year for Alnylam. A 16-year-long research project into RNA interference resulted in approval of Onpattro, the biotech's first commercial product and a landmark for the technology's development.
In the months since, company CEO John Maraganore has overseen the launch of Onpattro, which carries an annual list price of $450,000 for the typical patient. The Cambridge, Massachusetts-based biotech is also preparing for three Phase 3 readouts on other drug candidates from its pipeline next year.
If that's not enough, the exec is this year's chair of biotech's largest trade group, the Biotechnology Innovation Organization.
On Wednesday, Maraganore caught up with BioPharma Dive, discussing his future dreams for Alnylam (hint: nothing like big pharma), political pressure the industry faces on drug pricing and the recent controversy surrounding claims by a Chinese scientist of the birth of two genetically edited babies.
The following interview was lightly edited and condensed for clarity.
BIOPHARMA DIVE: Alnylam had a big year in 2018 with Onpattro's approval. How do you follow up on that in 2019?
MARAGANORE: I think we follow up on it in three very specific ways. One is we execute flawlessly on the Onpattro launch globally. That's a key thing because showing that RNAi therapeutics can get approved is step one. Showing RNAi therapeutics can make a broad impact in patients' lives and be commercially successful is definitely step two. And if you actually don't do step two, you make step one meaningless at the end of the day.
The second thing we're doing next year to make it equally brilliant as this year is we've got five Phase 3 programs that are ongoing with three Phase 3 program readouts. In an early part of the year, like March time frame, we'll have our porphyria readout. Then in the middle of the year, our partners at The Medicines Company will have their PCSK9 program readout. And then at the end of the year we'll have a Phase 3 readout from our primary hyperoxaluria program called lumasiran. There aren't a lot of companies out there that have five Phase 3 programs with three Phase 3 data readouts during the course of the year. I would say that's number two in our list.
And then, number three is to continue to show great execution on our overall platform, in our ability to generate new, sustainable innovation every year. We're going to have new programs that go into the clinic, we have earlier stage programs that'll have important data readouts, but clearly that's another important element as well.
A lot of the talk recently at ASH was on hemophilia gene therapies. How do you see gene therapies in relation to RNAi therapies? Are those potential competitors down the line?
MARAGANORE: I think it's more complementary. Typically, the RNAi approach is focusing on shutting down a specific RNA and protein. In contrast, gene therapy is focused on making a protein. More often than not, it's really the Yin and the Yang between those two technologies, which makes them wonderfully complementary for the treatment of human disease.
There are times in which we find a clever way to increase something, like in our hemophilia program where we can target anti-thrombin. We can increase thrombin generation and therefore bypass the need for factor. Those are a small number of examples where we arguably compete a little bit more with gene therapy.
It's our view that gene therapy is coming of age. It's an exciting new frontier for treating patients. But even in diseases like hemophilia, there will probably only be a small number of patients that ultimately use gene therapy as a way of managing their disease. And we expect many patients will look at a drug like fitusiran, which is our drug with Sanofi, and view that as being a very exciting alternative to the use of frequent IV infusions of factor.
Phase 3 trials are underway to really prove that out. But at the end of the day, we think patients will welcome approaches that are not permanent like gene therapy. Gene therapy does have that plus and also potential minus in a way that could be challenging for some patients.
Do you see an enduring distinction between a biotech and a pharma? Where do you see Alnylam falling within that in 10 years if the company keeps growing?
MARAGANORE: Biotech companies are risk-takers. Pharma companies are risk managers. They don't like to take risks.
I think there are examples of pharma companies that are becoming biotech companies. [Bristol-Myers Squibb] did that many years ago. Novartis is doing that as we speak. They're basically shedding their pharma roots of incremental innovation and looking for transformative innovation.
That's what biotech is all about. Biotechs have a risk culture. We'll take chances on opportunities to make a difference in patients' lives that a pharma company would traditionally never do because they just are too focused on managing risk as an approach. And that makes it a distinguishing feature that is sustainable even as a company like Alnylam grows in the future.
Where do you want to position Alnylam on that risk scale now and in the future? Do you envision Alnylam as a pharmaceutical giant?
MARAGANORE: No, please no. God no.
We want to continue to be an innovation-focused company that is willing to take risks in our business to obviously benefit patients.
And when we talk about risks, would you do a study in Alzheimer's disease based on a great piece of science or do you say, 'Oh my God, Alzheimer's is very risky, nothing ever works there, let's not do any studies there because it's likely to be a failure?'
The risk-taking culture which I'm talking about is having a science-based approach to solving a problem and being willing to test that hypothesis in a study that is probably not going to work because the chances are low. But it's worth trying for the benefit of the patients. That's a risk-taking culture that I think we have today as a company and we will maintain as a company for the future.
We've seen the Trump administration's drug pricing blueprint start materializing into policy proposals recently, namely with the DTC list price proposed rule and the IPI pricing model for Medicare. What do you make of the political attention your industry is under?
MARAGANORE: In this discussion, we are and have been and will continue to be an important voice to make sure that whatever policy comes up that is part of creating a sustainable future for pharmaceutical spending in the country. That at the end of the day, whatever's done does not harm the innovation that our wonderful country has, which is a global treasure. You think about the U.S. system for pharmaceutical innovation, we are log years away from any other country in the world and we want to preserve that in this country.
I do think policies like the two you mentioned are actually very deleterious potentially if they get embraced and enacted. I don't think they will succeed, but those two in particular are ones that are not good.
On the other hand, the industry can do better and Alnylam has stood out uniquely to look at things like drug price increases and say, no, we aren't going to do drug price increases. I think there ought to be more of that from the industry. We as an industry have to be part of the solution. We have to be part of working with other stakeholders, payers, policymakers in Washington, administration members, legislators, to basically be part of the solution here to come up with the right answer for our country that make sure that medicines can be affordable to patients while making sure that we preserve innovation that's delivered to patients.
The CRISPR controversy was a couple of weeks ago. I want to put that in context of skepticism on climate change and vaccines, this anger at drugmakers and big pharma on pricing and accessibility, and now new worries over this gene editing tool. Do you think the CRISPR news will feed that trend?
MARAGANORE: I think there is a concerning sentiment from our country's leadership around science and trusting science and believing in science. When you see the country pulling out of the Paris Accord, when you see the country [and] policymakers wondering whether vaccines are good or bad, that's a very, very dangerous situation. And one that I personally, I'm talking for myself personally, reject as an acceptable position by leaders of our country.
The gene editing story in China, on the other hand, I think that is obviously science, but it's something which we as a group of scientists have unilaterally said is too far too soon to go, to germline editing to fix things in a fetus. I mean, we don't embrace that yet as a scientific community and we firmly reject it because we don't yet know what the consequences are of that type of science.
Obviously, there's no doubt that the science around climate change, which is embraced by almost everybody, the science around vaccines which is incontrovertible, and the attack on that science is just not good. It's concerning. Hopefully, it's short-lived in many ways, and we can go back to being a country that focuses on the right scientific-based decisions for our society.
Things like gene editing of the germline, I would call that a rogue activity by a scientist who is off the reservation, who should not be doing that at this point in time and has been publicly questioned in terms of what he's done, and I think appropriately questioned for what he's done.
I've seen some articles trying to expand this case, noting concern over 'designer babies.' Are you worried how the public could react and if it will close out research opportunities down the line?
MARAGANORE: Yeah, I do worry about that.
That's why the response to that by the scientific community, but also by the head of the NIH and the head of the FDA and also by BIO was so clear in terms of our rejection of what was done. It's an act like that that can cause a knee-jerk reaction by the uninformed public and by the uninformed leaders of our country to do something which can be very harmful for future innovation. I do worry about that as well.