During clinical trials, the FDA may sometimes order a clinical hold. This order is often given to halt or suspend trial operations if the FDA believes that participants would be open to a significant risk of injury or illness, if the IND doesn’t contain enough information regarding the risk, or if there are some sort of issues with the trial. Earlier this year, the FDA placed a clinical hold on a Phase 1 clinical trial evaluating RP-A501 for patients with Danon disease. The hold was granted following potential conflicts with trial protocols, patient selection, and patient management. But according to a news release from gene therapy company Rocket Pharmaceuticals (“Rocket”), the FDA lifted this clinical hold as of August 16. Now, trial enrollment may continue.
RP-A501
So what exactly is RP-A501, the therapy being studied within this trial? According to the clinical trial page, RP-A501 is:
[an experimental] gene therapy product consisting of a rAAV9 capsid containing the human LAMP2B transgene which will be administered as a single intravenous (IV) infusion. Subjects will receive one of three dose levels depending on the cohort.
Within the clinical trial, researchers will evaluate the safety, efficacy, and tolerability of RP-A501. Currently, the trial is working to enroll a cohort of pediatric patients. Once these patients are enrolled, they will receive low-dose RP-A501 (6.7e13 vg/kg). Outside of this cohort, the treatment is also being evaluated in a similarly low-dose young adult cohort, as well as a high-dose young adult cohort (1.1e14 vg/kg). Data from the study should be available before the end of the year. However, preliminary data suggests that the treatment is relatively safe and well-tolerated thus far.
Danon Disease
Danon disease is a rare X-linked lysosomal storage disorder characterized by cardiomyopathy (a weakened heart muscle), myopathy (weakened skeletal muscles), and intellectual disability. LAMP2 gene mutations cause Danon disease. Typically, these mutations cause membrane defects in lysosomes. Because Danon disease is inherited in an X-linked dominant pattern, males are often more severely affected than females. Additionally, male patients often have earlier symptom onset. Unfortunately, the prognosis for this condition is somewhat poor. While affected females may live into their 30s, males with Danon disease often experience heart failure or death in their late adolescence to early adulthood. Symptoms include:
- Cardiomyopathy (dilated or hypertrophic)
- Weakening skeletal muscles, which often affect the upper arms, shoulders, neck, and upper thighs
- Intellectual disability (more common in males)
- Heart palpitations and/or abnormal heartbeat
- Chest pain
- Abnormal gait
- Gastrointestinal disease
- Breathing problems
- Exercise intolerance
- Vision abnormalities
- Cardiac preexcitation
Learn more about Danon disease.
