End-to-End Thinking is Key to Overcoming Friction in Gene Therapy Development

Abhishek Gupta, BS

Gene therapy and cell therapy products tend to be highly complex, and as such development and commercialization of investigational candidates poses a number of unique challenges. Many companies and institutions trying to bring these advanced therapies to market have been set back in terms of both time and resources when facing such challenges along the way.

Abhishek Gupta, BS, the senior vice president of genetic medicines at the contract research organization (CRO) Syneos Health, spoke at a sponsored symposium on this topic entitled “Unlocking the Promise of Genetic Medicines: From Clinical to Commercial Development,” at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, MD. Shortly before the symposium, CGTLive® sat down with Gupta to get his insight on the main challenges of bringing gene and cell therapies to market and the correct way to address them.

CGTLive: Can you give some background context about your session at ASGCT’s 2024 Meeting?

Abhishek Gupta, BS: I think one of the biggest things in our industry has been that we've seen a lot of innovation going to the clinic, and now with commercialization. We've learned a lot in that paradigm. The idea is, what do we do in the next 5 years or next 10 years to really move this field forward? We've learned a lot both in clinical development where you can run some of these trials more efficiently, as well as commercially you can make significant progress on getting these therapies to patients. What we focus on are the actual capabilities within the clinic and translating those commercially. Whether it's manufacturing high-cost therapies, transporting them across the world, managing oversight for them as they're embedded in different sites, or training the infrastructure that's not familiar with cell and gene therapies, executing on-time and on-budget trials is something that's in our wheelhouse. We're taking that model and lifting it and pointing it towards commercial because we think that commercialization of genetic medicines is a step out of clinical trials, but it's not a big step out, as has been traditionally thought about.

What are the main points you are presenting?

There's excitement as innovation in academia is translating into the clinic and eventually finding its way to patients commercially, but there's also friction. The friction is that oftentimes sponsors have to go back to the drawing board; either they didn't think about functional endpoints versus biomarkers, different regulatory bodies across the world with their different requirements, or about manufacturing in a robust way, whether they're optimizing for the clinical trial or for commercial. These friction points are things that we can help with and that we've been spending a lot of time thinking about with our clients and our customers. Then finally, just end-to-end thinking—what does that really mean, by putting the patient in the front and center? What it really means is you have to think about the entire set of stakeholders, so not just the sponsors and the manufacturers, but also the regulators and most importantly the [patients]. These are probably the most important stakeholders across the globe. Then what's really hidden and what's really valuable are the sites themselves. The way that the sites administer these, research these, and implement them is really unique to them. Commercially, we need to think about sites and physicians as a key stakeholder and not as an afterthought.

How would you summarize the main takeaway of this for doctors and the broader healthcare community?

I think the biggest takeaway is that there's reason for hope for our field, but there's a lot of work that needs to be done. These are one-time treatments, but that also means we only have one time to get them right. There's a lot of burden to get that right for CROs, like Syneos and we're committed to that. I think that's one of the biggest takeaways to interacting with physicians and sites and the unique site setups, if you will. Then the other takeaway is that in order to operationalize this hope into reality, it's not going to happen by hope alone, or chance alone, or science alone. It really does take a collaborative effort across the industries, from contract development and manufacturing organizations, to CROs, to sponsors and doing everything with a practical mindset. That's going to be in the long-term the best approach that's going to add the greatest value to patients and the healthcare providers that provide that therapy.

Can discuss some of the specific challenges in this space?

Well, I think we kind of know the toughest ones. These therapies are developed in labs or in small trials, with 15 patients sometimes, and now they have to be pointed towards larger trials. Many times sponsors go back to the drawing board. I think these pain points are a little bit obvious at this point so now what we're trying to do is operationalize that and think end-to-end even prior to these therapies getting into the clinic. We just should have an approach on how to do the full clinical trial all the way from phase 1/2 to phase 3 and even beyond, and how you're going to operationalize that from lighting up the stakeholders, lighting up the sites, lighting up the patients, and having a really robust understanding on the assumptions on enrollment. These are the friction points and the challenges that we're hoping to address at Syneos.

Is there anything else you would like to share?

I think ASGCT is a wonderful conference. Over the years, it's evolved quite a bit. Adeno-associated virus vectors are a mainstay workhorse that are going to be around for a long time and are derisked commercially. We've seen that play out in the clinic, where a lot of sponsors early on really like certain vectors, if you will, and they iterate around capsids and then into indications—versus the nonviral vector approach, which is just still starting out. I think that's one of the trends we're seeing play out materially. We're really excited about this field and really happy to be here at ASGCT.

This transcript has been edited for clarity.

Click here to view more coverage of the 2024 ASGCT Annual Meeting.

REFERENCES
1. Gupta A. Unlocking the Promise of Genetic Medicines: From Clinical to Commercial Development. Presented at: ASGCT Annual Meeting 2024, May 7-10; Baltimore, Maryland.