ViTAL Meets Pushkal Garg (Alnylam CMO)
Last Thursday, ViTAL hosted Dr. Pushkal Garg of Alnylam to hear more about Alnylam & RNAi (RNA interference), Clinical Drug Development, and Dr. Garg’s career as an MD/ professor to now the Chief Medical Officer of Alnylam.
This article summarizes the lessons and my key takeaways from the event.
Introduction
“Find Your North Star”
Dr. Garg’s unique background as a biochemist, MD, healthcare policy instructor, and clinical development lead explains why ViTAL members were captivated throughout the presentation.
From explaining how acute hepatic porphyria disease occurs (hint: it has to do with heme and ALAS1) to explaining how clinical trials work for rare diseases, Dr. Garg highlighted one of the key skills that all ViTAL members aspire to cultivate—being able to translate science, business, and regulatory languages to common language—and with passion.
His passion for realizing Alnylam’s vision to harness a revolution in biology for human health was bold and contagious.
Alnylam & RNAi
Alnylam was founded in 2002 with the mission of building a top-tier, independent pharmaceutical company founded on RNAi (RNA interference). The company is translating Nobel Prize-winning science, RNAi, into a whole new class of medicines that are treating diseases with high unmet needs.
A Crash Course in RNAi
Dr. Garg spent some time to explain the differences between traditional rx (e.g. small molecules and biologics that target proteins) vs. mRNA Rx/ Oligonucleotide Rx/ RNAi (e.g. targets RNA or the translation process) vs. Gene Rx & DNA Editing (e.g. targets DNA).
I won’t go too much into details here, but if you are interested, take a look at NCBI’s probe here or one by Nature here. The process is actually quite fascinating (after all, it won a Nobel Prize) and not that hard to understand.
TL;DR? Just understand that RNAi “silences” the targeted disease-causing genes which in turn blocks the production of disease-causing proteins. This is ground-breaking technology that won Nobel Prize and took Alnylam $2.3 billion to turn the technology into therapy.
Clinical Drug Development
Drug development costs a lot of money (read: an average of $2.6 billion) and time (read: an average of 10 years). And even worse, not all of them make it to market. In fact, less than 12% of the drugs that made Phase 1 clinical trials will be ultimately approved by the FDA.
If you are not familiar with the drug development process, check out this recap of the Drug Development Process (FDA).
What was really interesting to note during the presentation was that companies that are developing therapies for rare diseases go under a modified process. In other words, the clinical trials for rare diseases do have to meet the same requirements as common diseases but may follow a shorter timeline.
In drug development for common diseases, phase 1 tests for safety and phase 2 tests for efficacy; in rare diseases, the boundary between phase 1 and 2 is not as clear. In addition, the size of test subjects differ. This makes sense as in rare diseases, patients are often in a dire need of treatment (i.e. there’s no treatment available now) and are smaller in number.
Questions and Answers
Following the presentation, ViTAL members had a chance to ask any lingering questions. Here are some of the questions our members asked:
Why rare disease?
There are many monogenic diseases in the rare disease space. Compared to multigenic/multifactorial diseases like diabetes, monogenic diseases are easier to target and more suitable for RNAi.
Why is drug development so expensive?
Often, a good chunk of money goes into finding patients (test subjects) + running the actual trials. It’s important to note here that the low number of test subjects (as often in the case of rare diseases) yields more complexity than running clinical trials with a large group.
It’s also interesting to note here the startups that are working in the space of bettering clinical trials process and matching patients to clinical trials.
Here are some startups that come to my mind:
- 23andMe (https://www.23andme.com/)
- PatientsLikeMe (https://www.patientslikeme.com/)
- 3billion (https://3billion.io)
Where would one find patients with rare diseases?
World’s leading experts in rare diseases; they often have a long-term relationship with patients.
What were some of the learnings you’d like to share with your younger self?
- Be a team player—unless you are an artist or a writer, you will spend the majority of your career working in teams.
- Develop leadership qualities—being a leader entails three things: 1) you are able to understand a complex problem, 2) set a vision, and 3) mobilize people collectively to develop a solution.
- Intellectual curiosity—always be willing to learn (on a personal note, I think this advice is absolutely critical. I received the exact same advice from Walter Isaacson, the ex-Chairman of CNN & writer of Steve Jobs’s, Einstein’s, Benjamin Franklin’s, and Leonardo da Vinci’s biographies).
Thank you, Dr. Garg, for sharing your story and inspiring the next generation of healthcare entrepreneurs and innovators!
ViTAL is Northeastern University’s Hub for Healthcare. We are a student-run organization that aims to empower the next generation of healthcare entrepreneurs and innovators by providing learning, connections, and resources beyond the classroom.
Please contact vital.northeastern@gmail.com or kim.jooy@northeastern.edu to learn more about ViTAL.
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