The Phase I study could potentially result in RP-A501 becoming the first gene therapy for monogenic heart failure.
On February 28, Rocket Pharma broadcast a special event hosted in New York City celebrating Rare Disease Day. “Patients and caregivers affected by rare disease may be Rare, but Not Alone,” stated the description.
During the event, a family with two generations affected by Danon disease shared their story. The mother, Dawn, described the beginning of her experience with the disease back in 2016, when her son began suffering symptoms. Though they visited doctor after doctor to seek treatment, they were unable to find a solution.
It wasn’t until years later that genetic sequencing revealed that both Dawn and her two sons had Danon disease. The mother remarked that her diagnosis saved her life.
Dawn described a few challenging aspects of the family’s day-to-day life, such as struggles to get her son to want to go to school on harder days. Due to negative side effects from medication, the family makes efforts to avoid the sun despite their living in Florida. Dawn shared that she sometimes finds daily activities like cleaning difficult. “I constantly live in worry,” she said.
Keynote speaker Moris Danon, M.D. identified the disease in 1981. The doctor’s main message to the patients, families and scientists in the room was “don’t despair; we’re really working very hard on it.” He noted that many scientists are working persistently to find cures that help patients with rare diseases.
Rocket Pharma is one of the groups doing this work. In an interview with BioSpace, Kinnari Patel, president and COO of the company, outlined the gene therapy work they are doing. “We treat diseases with no other treatment options. The only standard of care for these diseases is transplant, such as heart or bone marrow transplant. These are the definition of life-threatening diseases.”
She described a few of the unmet needs associated with Danon disease that Rocket is working to address. “Imagine that you have a bunch of marbles and dirt and dust spread on a hardwood floor. That’s what happens to the tissues in Danon disease. They collect debris. The heart becomes larger and abnormal. It can’t pump blood across the body. It can lead to multiple clinical manifestations.” She explained that heart failure is the leading cause of death in the disease.
Rocket’s RP-A501 is currently being evaluated as a therapy for Danon disease in a clinical trial. Patel continued to explain her debris analogy, noting that “gene therapy is like a vacuum cleaner that cleans it all up. The cells become normalized, which we’ve shown both in mice and in humans. Circulation improves, the heart improves and patients can live a longer and healthier life.”
So far, the clinical trial has treated six patients. The first four older pediatric patients were followed for up to two years. “All of them have had an improvement in biomarkers, as well as clinical NYHA-class association improvements, which marks the severity of heart deterioration. We are currently treating a pediatric cohort from ages eight to 14. We will have more data later this year. If these two patients do well, we will take this study to Phase II.”
She described a family involved in the clinical trial that has two sons with the disease, though only one son participated in the trial. “We have one kid who had to use a scooter to go from classroom to classroom. He couldn’t hold a job and couldn’t play sports. Now, he’s applying to colleges and looking forward to living a normal life. His brother is approaching confinement to bed based on his disease expression.”
The study could potentially result in RP-A501 becoming the first gene therapy for monogenic heart failure. “Gene therapy can be curative in a way that no other medicine can. The reason is that you’re replacing the gene at the DNA level. DNA is the core of who we are as physical beings,” explained CEO Gaurav Shah, M.D.
The therapy uses an Adeno-associated virus (AAV) to replace the mutated gene with a corrected version.
“We attach a corrected version of the gene, then we space shuttle the cargo onto the virus. We reinfuse it into the patient’s body. AAV9 loves to go to the heart. It automatically goes there and sets up shop, then expresses and turns on the gene that’s missing in Danon patients,” Shah said. “Of course, there’s a lot more nuance to it. Rocket and our clinical and science teams have figured out this art of gene therapy that effectively remodels patients’ hearts.”
He said that “of all the forms of cardiomyopathy, Danon disease is probably the most aggressive. The heart grows thickest and fastest in the most rapid way. All the other similar diseases have slower progressions, even the other genetic ones. This is the only disease where an eight to 10-year old can get a thick heart rapidly. If we crack this, we can cure things in a large way for heart failure overall. It opens the door to other clinical possibilities.”
Patel wishes that more people were aware of the genetic testing that’s easily available, especially when they have symptoms of Danon disease or other rare diseases themselves. “I wish people who thought they may have symptoms would get their genes tested. With heart transplants and gene therapy, they can be treated. The earlier you intervene, the more we can prevent the disease from progressing.”
Patel also highlighted the patients and families who are working to raise awareness of the disease, such as Jenny Hsieh, Amy Atkinson and Kim Marincik, the women who started the Danon Foundation.
“I want to highlight that in rare diseases like this, patients and advocates have a huge burden of unknowns and complexity. If we can unite rare disease patient communities together, we can tackle more,” she said. “The people doing this are going above and beyond, taking care of their own diseases, and taking care of their kids and families. They’re the true heroes.”
