Beyond The Printed Page | March 19, 2018

4 Questions With John Maraganore, CEO Of Alnylam Pharmaceuticals

Source: Life Science Leader
Rob Wright author page

By Rob Wright, Chief Editor, Life Science Leader
Follow Me On Twitter @RfwrightLSL

4 Questions With John Maraganore, CEO Of Alnylam Pharmaceuticals
John Maraganore (L), CEO of Alnylam Pharmaceuticals, and Rob Wright (R), January 10, 2018.

When I sat down to interview John Maraganore, Ph.D., CEO and director at Alnylam Pharmaceuticals, for the April 2018 issue of Life Science Leader, it was while we were both in San Francisco for the 36th Annual J.P. Morgan Healthcare Conference (JPM). But our conversation actually began in the hallway of the Marriott Marquis on Mission St. Walking to the interview room we talked about a variety of topics, including how and what we are both doing in our roles for the Biotechnology Innovation Organization (BIO). It was last June when Maraganore was elected as the new chair of BIO, our industry’s biggest trade association, while at the same time I took on the responsibility of co-chairing the BIO education planning committee for the 2018 BIO International Convention in Boston. I admire Maraganore for his willingness to give back to the biopharmaceutical community. Past chairs have shared how the role is certainly not a figurehead position, and doing a good job can be extremely demanding for even the most organized of executives. But let’s specifically consider what all Maraganore had going on in his day job of leading one of the hottest biopharma’s in 2017.

Alnylam began 2017 with a stock price of $38.15/share. Yet it ended the year up more than three times that (i.e., close of $127.05/share on 12/29/17). This is pretty remarkable when you consider the September decision to place a hold on all clinical trials involving fitusiran, Alnylam’s investigational RNAi therapeutic targeting antithrombin for the treatment of patients with hemophilia A and B. As you might guess, the company must have had a bit of good fortune in addition to such adversity. Here is just a sampling.

  • received PRIME designation (March) from EMA, followed by Breakthrough Therapy Designation (May) from the FDA for accelerated assessment of givosiran, Alnylam’s investigational RNAi therapeutic for the treatment of acute hepatic porphyrias
  • announced positive Phase 3 results (September) of APOLLO trial for patisiran, a potential treatment for hereditary ATTR (hATTR) amyloidosis patients with polyneuropathy
  • received accelerated assessment (EMA) and a Breakthrough Therapy Designation (FDA) for patisiran in November
  • had its clinical hold on fitusiran lifted by the FDA in December

All of this positive news has positioned 2018 to be a transformative year for Alnylam, which you can read more about in the April issue of Life Science Leader. But one of the challenges we often face in producing a print publication is there isn’t always space to share all of the great insights derived from interviewing an executive like Maraganore. This is one of the reasons we created our exclusive, Beyond The Printed Page section on our website. And while access to this continues to be free, to read the comprehensive feature involving Alnylam Pharmaceuticals you need to be a subscriber — which you can do here. We hope you enjoy this latest Beyond The Printed Page installment.

How Does Executing A Clinical Trial With A Collaborative Partner Compare To Going It Alone?

Going alone requires a much more intense resource requirement than when working with a partner. That being said, collaborating on a Phase 3 trial still has a lot of moving parts. You’re providing assistance on regulatory questions and answers. You’re helping on design aspects of the Phase 3. You’re tapping into your experience with the platform from other clinical studies. However, starting your own Phase 3 is totally different. You have your clinical operations team up and going. Your medical affairs team has been activated and is working to help identify patients. While going alone requires greater reliance on your own internal resources, it also seems to come with a slightly higher amount of intensity. But going alone isn’t really going alone, as we have master agreements with two CROs (i.e., Medpace and PPD) to help execute these trials.

How Involved Are You Personally With These CRO Relationships?

I personally view a CRO as a partner, not as a service provider. Barry Greene (Alnylam’s president) and I have taken an active approach in developing relationships with these organizations and communicate regularly with August Troendle, CEO of Medpace, and David Simmons, CEO of PPD, to gain alignment on business interests and pipelines. If you strive to create an environment where they understand your genuine interest in helping their organization to be successful, it is much easier to communicate when our collaboration encounters an issue.

In 2013, We Talked About Alnylam’s Approach Of Being Open When It Comes To The Sharing Of Its Science. What Have Been Some Of The More Recent Positives And Negatives Of Such An Approach?

Historically we have been very transparent and open to communicating our science and clinical results. That approach has helped solidify Alnylam as a trusted brand with investors, scientists, clinicians, and regulatory authorities. When Alnylam presents Phase 3 data, we do it in a very comprehensive manner and put everything on the table. Our approach of full disclosure is very different when compared to other companies, and has become a part of the Alnylam heritage that we are very proud of. To take that a step further, on the Alnylam website we created Capella, an area dedicated as an open-access archives for all of our RNAi published research and presentations. One of the downsides of being open about your science is it can be enabling of competitors. We are fine if a competitor uses our publically available information to pursue their own competitive path forward. Further, we realize that this process of sharing educates the outside world about our approach, and to some extent, our medicines. So while we are OK with helping a competitor become more effective, this doesn’t mean we don’t protect our discoveries with patents as well as keeping some of our discoveries and development strategies as trade secrets. As a result of protecting our discoveries, similar to other companies in our current stage, either on the cusp of being commercial or with products in the marketplace, we have a number of active litigations that I can’t really comment on. But I can tell you that we feel very strongly about the merits of the cases in which we’re involved, and Alnylam will vigorously protect our intellectual property as well as defend itself strongly when threatened with litigation by a party whose claims have no merit.

What About Alnylam’s Future?

Alnylam has seven programs in clinical development, including patisiran. Of these, three are in Phase 3 development, and the others are either in Phase 1 or 2. So we are much more than a patisiran company. The three programs in Phase 3 behind patisiran, from our own clinical pipeline, position Alnylam’s product engine to deliver a new product every 12 to 18 months for the next several years. We believe that executing on that level of productivity will allow Alnylam significant growth toward becoming a top biopharma in the industry. In addition, we believe Alnylam’s current clinical pipeline, combined with its early product engine, has the ability to generate two to three new clinical programs a year. Regarding patisiran, there are additional studies we will do as part of Phase 4 development toward improving the product’s profile, not to mention the subcutaneous (Sub-Q) version of patisiran (i.e., ALN-TTRscO2), which will go into Phase 3 development this year.