Rocket Pharma's Modality-Agnostic Approach To Rare Disease

By Tyler Menichiello, contributing editor

Cell and gene therapies have, from their very inception, offered hope to millions of patients. However, more immediately, they offer hope to thousands of patients around the world with rare diseases. Recently, I had the chance to speak with Rocket Pharmaceuticals’ president, COO, and head of R&D, Dr. Kinnari Patel. She told me about the company’s modality-agnostic approach to treating rare diseases, as well Rocket’s pipeline of six disclosed programs spanning lentiviral (LV) and adeno-associated viral (AAV) gene therapy platforms.

Indication Over Technology

A lot of companies in the cell and gene therapy space are, as Patel describes, “technology-based companies looking for diseases.” While Rocket’s pipeline consists of gene therapies that utilize LV and AAV technologies, Patel makes it clear that the company isn’t “married” to any one technology or platform. If a new platform becomes available that seems like it has promise to treat a rare disease, she says, Rocket isn’t afraid to recruit the best scientists and talent to develop a treatment. “We don’t need to be first in technology, we just want to be first in the disease,” she says. “To us, that’s the most important component.”

Her criterion for Rocket’s R&D pipeline is simple. “One, is there a disease that has unmet medical needs? Two, is that a monogenic disease? And three, are there no treatment options available?”

“There are some diseases that many companies go after simply because it’s a big market,” she tells me. “We don’t want to be the third, fourth, or fifth to market. We want to work on therapies where there’s a true unmet need.”

Challenges Facing Rare Diseases

Developing cell and gene therapies is never an easy lift, but doing so for rare diseases adds another layer of complexity. One of the biggest challenges inherent to rare diseases is the availability of — and access to — patients. “Most patients go through five or seven doctors before they actually even know what disease they have,” says Patel. “If you’re a drug developer, and you need to find patients, how do you find them before it’s too late? That’s why genetic testing and promoting this testing is really critical.”

This challenge is made more difficult by these patients’ often critical conditions. “The one thing I have to stress with any cell and gene therapy product, especially in devastating diseases, is that the sense of urgency is very real for these patients,” Patel says. She recalls a tragic example: In the time it took for Rocket’s IND to be filed for Kresladi, three of the patients identified for the study passed away. “Trying to get everything done in a way that makes sense, with the highest quality of product, while balancing the urgency that patients have, is really critical.”

Another key challenge is designing clinical trials that consider the natural history of the rare disease in question. For most rare diseases, disease progression, as well as how patient outcomes compare with and without the gene therapy, are not understood. Natural history studies provide valuable insights into understanding the disease and serve as comparators to clinical trials, Patel tells me. For Kresladi, Rocket worked closely with patients’ treating physicians and regulators to come up with primary and secondary endpoints. “We had discussions every step of the way, sharing our data and understanding what the endpoints mean and figuring out how to interpret data as it becomes available on a real-time basis, because this wasn’t a traditional, double-blinded, controlled study. It’s a single arm study that’s open label.”

Of course, with such rare indications and advanced therapies, there isn’t an abundance of regulatory precedent to develop these therapies. “How do you actually work to get these drugs approved efficiently when there are very limited regulations or precedents? It requires a lot of unique, one-off conversations and discussions.”

Leveraging Learnings

When it comes to developing cell and gene therapies, managing CMC is critical — particularly when it comes to LV-based gene therapies that require multiple steps in the treatment and manufacturing process. Rocket experienced this firsthand through the receipt of a Complete Response Letter (CRL) from the FDA on June 28 regarding its latest-stage program, Kresladi — a gene therapy for patients suffering from leukocyte adhesion deficiency-I (LAD-I), a rare and often fatal immune disease. This CRL requested additional information about CMC to complete the FDA’s review of Kresladi. “We are engaging in productive dialogue with the goal of approving Kresladi as quickly as possible,” says Patel.

The unique thing about Rocket Pharmaceuticals, according to Patel, is that its first drug (Kresladi) is not the company’s biggest.

“We’re making this therapy available because there are patients that really need it,” she explains. “Learnings from this launch will help create foundational capabilities that we will draw upon to launch RP-L102 for Fanconi Anemia, which is our second BLA and first MAA that’s coming up.” After that, the company plans to apply these learnings to additional assets in development, notably through our AAV gene therapy platform with its biggest program, RP-A501, for Danon Disease, which Patel is excited about for two reasons.

“One is that this is the first time any company’s shown that a gene therapy could work for cardiac disease,” she explains. “Number two, it’s designed as a one-time, AAV gene therapy, which is delivered through a single IV-infusion and specifically designed to target the heart. So, this really consolidates and condenses the time a patient gets access to therapy.”

Beyond Rare Diseases

Overall, Patel feels positive about the trajectory and future of cell and gene therapies — for rare disease patients and beyond.

“Cell and gene therapy isn’t something that’s cool today and gone tomorrow,” she says. “I really believe this is the next wave of innovation. We can change humanity and ensure that patients’ DNA doesn’t define their destiny in a negative way.”

Though the industry is still in the initial stages of innovation and development, Patel believes these therapies and technologies will eventually be used to treat (and potentially cure) more common diseases.

“In theory, gene therapies can address any disease that’s caused by a genetic mutation,” she says. Successfully treating conditions caused by single mutations can open the door to treating conditions caused by multiple mutations, which would address much larger populations of people. “Heart disease, strokes, and Alzheimer’s may actually be the future of gene therapy after success is found in treating rare diseases.”

“We’re still in the forefront and learning a lot, but hopefully, through collaboration and curiosity, we’re going to change the world."