Advancing Treatments for Rare Diseases Requires a Team Approach

Monday, February 28, 2022, is Rare Disease Day, recognizing the more than 300 million people worldwide affected by one of more than 7000 diseases designated as rare. Gene and cell therapies are being developed for the treatment of a wide range of rare diseases such as Pompe disease, muscular dystrophies, Danon disease, and more. As part of an expert-led roundtable, CGTLive spoke to leaders in both the clinical and biopharmaceutical fields to get their feedback on how cross-collaboration between industry, academia, and advocacy can help advance the management and treatment of rare diseases.

CGTLive: How can we improve collaboration among the different stakeholders to ultimately improve education, awareness, and treatment of rare diseases?

Barry Byrne, MD, PhD; director, Powell Center for Gene Therapy, University of Florida: While there are always resource constraints when dealing with an orphan indication, the threshold for interest by pharma companies in what's an economically viable treatment for drug development activity is significantly higher than most populations than those that are faced with rare disease problems. We rely on those that are not affected by rare diseases to help support those communities and on global organizations like the Muscular Dystrophy Association to be an aggregating factor for the whole neuromuscular community. That brings us shared resources and is one way we can accomplish what's needed in this area.

Paul Wuh-Liang Hwu, MD, PhD; professor, pediatrics, National Taiwan University Hospital: We have been working with several groups now for quite a long time to improve education to better try and capture companies’ development interests. We also keep in mind the interests of the patients. We're trying to improve diagnosis, so we try to get help and resources from patient organizations and companies interested in the disease to be able to offer more convenient, maybe free-of-charge, diagnostic services to doctors. It's difficult to diagnose rare diseases and suspicions are usually not accurate. So, we try to bring resources to decrease the difficulty, to decrease the burden to the physicians and finally, to improve diagnosis rates, and hopefully get treatments developed.

"There are so many diseases that have no treatment options, but if we bring the brilliancy in the science and technology and the products and molecules we have in our array of research together, as so many biotechs and pharmas have done, we could actually tackle many more diseases." - Kinnari Patel, PharmD, president and chief operating officer, Rocket Pharma

Bruce Dezube, MD; senior vice president and head of clinical development, Mustang Bio: Rare disease brings together government agencies, including both the funding and the regulatory agencies; the pharmaceutical industries; and patient advocates. Their priorities can sometimes differ. For patient advocates, I would say their priority is getting treatments developed. We say that patients are often on the different side of the stethoscope than the providers. So where can things improve? I think patient advocates can often leverage their voice into streamlining clinical trial design with the FDA by perhaps helping to lower the chemistry manufacturing control (CMC) hurdles with the FDA to get more therapies approved. But also, enrollment to clinical trials is a tough battle and patient advocates can also help to really get the word out there. All these groups are involved with every aspect and every aspect is working, but every aspect could be working even better.

Kinnari Patel, PharmD; president and chief operating officer, Rocket Pharma: I think we're doing a fairly good job within our diseases and our ecosystem. What I would love to ambitiously do is to bring all the biotechs and pharma together. There are so many diseases that have no treatment options, but if we bring the brilliancy in the science and technology and the products and molecules we have in our array of research together, as so many biotechs and pharmas have done, we could actually tackle many more diseases. If we partner with top authorities and their regulatory advocacy teams, we can create a platform to make drug development more efficient, so more patients can have access to better therapies or any therapies.

So, my goal is to partner up and make the rare disease efforts bigger and bigger. I think the most rewarding part for Rocket was when we lit up the Empire State building for the first time about 4 years ago. We got messages from all around the world, from patients that said, my child or I myself have a disease that no one's treating, but for that one night, I didn't feel alone, and I felt there's hope for us and my family. Just a simple task of lighting up houses or monuments around the world could give that hope and make rare diseases something that we can really tackle together as a challenge.

Michael Singer, MD; cofounder and chief scientific officer, Cartesian Therapeutics: Overall, I have a very high opinion of the amount of collaboration happening, starting with our federal institutes, the NIH, and various programs. The funding agencies have shown a terrific devotion to rare disease research, and we do see lots of cooperation among biotech and pharmaceutical sponsors, rare disease societies, and patient advocacy groups, and patients and families themselves.

One thing, as a biotech researcher, that I have seen as a challenge in the past is when there are a small number of experts at academic universities who can be protective toward these patients and may not want to cooperate with industry and biotech, it's very difficult for industry to develop therapies for those patients. This becomes a barrier for biotech companies with potential therapies to offer those to the patients.

Michael Parini; chief executive officer and director, Freeline Therapeutics: I think drug discovery and development is a team sport. That includes biotech companies, academic collaborators, and the patient voice, which is especially important to advocate for participation in clinical trials, since that's how we advance science. I do think that there's a lot of good relationships there that have been built, but we still have some silos to break down. I think academics bring tremendous insights into the early work, and opening their doors and having a more constructive relationship with biotech companies is an important step. I really do see tremendous alignment between what we're all trying to accomplish.

Collaboration with regulators can be challenging and sensitive, but they certainly play an important role in making sure that the treatments and the clinical trials we conduct are appropriate and have the right benefit-risk profile for patients. As we push the boundaries of scientific exploration, we have to adjust the system a little bit and really re-examine meaningful endpoints and approvable packages, particularly for rare diseases. How should you structure a clinical trial where patients have lots of different variations in their genetic code, but they have the same manifestation of disease? Can we think about doing more clinical trials dependent on biomarkers and other ways of showing progression of disease, particularly in these severe diseases?

Lastly, patients, academic centers, and treating physicians have a lot to offer in that conversation with regulators. And I think that more of a bridge needs to be built. All those groups have to come together to make sure that we're all collectively working in the same direction to get to the ultimate goal to help people with serious, rare conditions.

Content has been edited for clarity.