Isaac Erickson, DiscGenics (UT, USA), discusses their allogeneic cell therapy for degenerative disc disease at Phacilitate Leader’s World and World Stem Cell Summit 2020 (FL, USA), as well as scaling up and dealing with different regulatory markets.
Can you please introduce yourself and tell us a little about your current role?
My name is Isaac Erickson. I’ve been at DiscGenics (UT, USA) for about four and a half years now. DiscGenics is focused on developing a cell therapy for lower back pain and my role is Director of Bioprocess Engineering. I work mainly on assessing and selecting technologies to enable the scale-up of manufacturing of our product.
I also have a role in Global Market Development – with a specific focus on the Japanese market – and assist in logistics handling of the shipments of our cell therapy to both the US and Japanese clinical sites where we are currently have two clinical trials underway.
Can you explain what degenerative disc disease actually involves?
The intervertebral disc is comprised of a number of different tissues, with the innermost portion of the disc being the nucleus pulposus. It’s composed of a proteoglycan-rich gelatinous core that provides cushioning and strength for the entire disc, and is surrounded by a fibrous annulus tissue.
When the nucleus pulposus starts to break down, it tends to be progressive and does not self-heal. That leads to a number of other degenerative sources of pain and eventually it will collapse completely. This can then be compounded, and cause debilitating pain, nerve impingement and a host of other complications. Current mild-to-moderate treatments are non-regenerative and attempt to mask the pain but do little to stop the progression. In addition, back pain is the most common non-cancer reason for opioid prescription in the U.S..
As the disease progresses, sometimes a patient’s only option is spinal fusion, in which the disc is removed and replaced with a bone substitute and impant fixation. The objective of such a procedure is to fuse the vertebral bones in place, preventing nerve and bone impingement. But, ultimately, fixing that joint completely with a surgical procedure, is costly and oftentimes doesn’t eliminate the pain all together.
What we’re trying to do is to intervene when people have experienced the chronic pain associated with degenerative disc disease and correct it before it becomes exceptionally bad. Our treatment aims to help regenerate that disc and bring it to a non-painful state, and we hope the duration of that relief is a very long period, but our clinical trials will help us really understand that.
How is DiscGenics combating degenerative disc disorder?
In our manufacturing process, we expand and re-differentiate these donor-derived intervertebral disc cells near to their original phenotype with the intent that they still have the innate ability to generate extracellular matrix. That means we’re then enriching that degenerated disc in patients with specialized cells that can enter and secrete the right factors and extracellular matrix proteins to rejuvenate and restore the disc to its former architecture, reducing pain in the process.
The mechanisms of action would be twofold. In addition to developing the new extracellular matrix that helps restore the architecture, the anti-inflammatory cytokine milieu that these cells have the ability to secrete would immediately alleviate pain through anti-inflammatory cues.
Could you tell us a little bit about what you talked about at Phacilitate?
I presented in one of the manufacturing sessions. The focus of the group was talking about process development, with an eye towards the successful scale-up and commercial development of manufacturing processes for cell therapy. My talk focused on some key points around scaling up and the considerations required to successfully scale-up a cell therapy. Our cell therapy is an allogeneic cell therapy, so there were some particular recommendations around that.
You were talking about allogeneic therapies in your talk, but they can have potential issues. How did you deal with these challenges?
We are making an allogeneic cell therapy derived from donor-derived tissue, so there are still donor-related issues. A single donor lot goes through our process and can generate many units of therapy, but the next time we produce a lot it’s from a new donor. That means we have some similar considerations around donor variability that an autologous cell therapy may have.
The other challenges we face are around scaling up efficiently, so that we can reduce the cost of our product and make it really accessible. Lower back pain is a severe condition and we want to be able to treat millions of people. For that, we really need to drive costs down and make the treatment accessible to that population.
That means we have to select manufacturing modalities that are compatible with our cells, preserve the phenotype necessary for their efficacy and also allow us to produce larger quantities in a single lot, which is something that wasn’t the main focus when developing clinical trial doses, but certainly is the mandate for developing a commercially successful cell therapy.
You’ve worked with regulators around the world; how have you found working with them and what sort of lessons do you pass on?
One of the key things we found is that they really valued data. In the US, we had a really nice package of preclinical safety and efficacy data. That propelled us towards, not just a Phase I, II or III program, but a Phase I/II study design, where they felt confident enough about the safety that they let us combine the Phase I/II into a single trial. This really gave us a leg up in our regulatory pathway. I think the quality and quantity of data you can provide regulators in the US really helped our case there.
A similar trial design was approved in Japan, albeit a little bit smaller and with a different control – which spoke to the flexibility and the logic of the Pharmaceuticals and Medical Devices Agency (PMDA; Tokyo, Japan). We explained that the controls we were utilizing in the US could be improved by utilizing a sham control as the control group for our study in Japan. Now, between the two trials, we have three different controls, which I think will provide a very interesting data set.
The other thing I found in Japan is that they have a very strong focus on raw materials, which certainly has merit. They really want to protect the safety of the population that may be receiving the therapy as part of a clinical trial, so they put a really strong emphasis on that. It really challenged us to gather the right documentation and give the right evidence to support our raw material selection, which was useful. It was a useful effort in preparing us to understand the expectations when we go back to them for a license application.
There was definitely a difference between the US and in Japanese markets. The Japanese market really emphasized commercial level requirements; whether it was viral testing, potential viral safety of biological raw materials, and the documentation required around any manufacturing processes of your raw materials that that are intended to reduce the potential viral load.
Degenerative disc disease and chronic back pain are not uncommon. Why do you think there’s not been more cell therapy treatments in the field?
There are some products out ahead, but given the market size, you would think that there might be more out there. I see similarities to arthritis in the knee and there’s been several manufacturers who have gone after that indication. Perhaps, with the recent successes of cell therapies to treat cancer, a lot of focus has been shifted towards products in that realm, where there’s a platform that can be utilized for so many different cancer applications. That opened the floodgates for a lot of drug developers to get into the cell therapy market with cancer targets. I think it could have diverted some of the focus from orthopedic applications for cell therapies.
Now, lower back pain may not be life-threatening, like cancer indications, but it is debilitating and has been recognized as a serious condition with an unmet need. For this reason, we received a Fast Track designation in 2019 by the U.S. FDA for out IDCT. We’ve really made it our mission to find an interventional therapy that potentially could be better than just an incremental improvement in their standard of living. It may give us the opportunity to potentially treat millions of patients, help them with their degenerative disc disease and maybe delay or prevent the need for more invasive interventional treatments like spinal fusion.
When it comes to back conditions, the market has some bad faith players in it. Do you ever worry about how those individuals can affect a company like yourself coming through with a genuine treatment?
Yes, absolutely. I regularly get mailers in my mailbox for clinics or physicians who offer an undescribed, unregulated, unapproved cell therapy for lower back pain and other orthopedic conditions. DiscGenics has made a point of choosing the correct and conservative “regulator approved” pathway to prove the efficacy of our treatment before we inject patients.
Unfortunately, there are players out there who will capitalize on the pain that people are in to charge a premium on therapies – whether they’re autologous or not – that have not been reviewed through the proper regulatory channels for those indications and they often make claims that are neither proven nor approved. There’s not a whole lot we can do about it other than put our name out there and make sure people understand that there is a correct path to proving efficacy. We’re doing our best to do exactly that. In the meantime, we hope that the FDA (MD, USA) continues to crack down on these types of clinics who are making incorrect claims, unauthorized for these types of cell treatment.
The opinions expressed in this interview are those of the interviewees and do not necessarily reflect the views of RegMedNet or Future Science Group.