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FDA Places Clinical Hold on Epilepsy Agent RAP-219 for Diabetic Peripheral Neuropathic Pain
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Key Takeaways
- The FDA's clinical hold on RAP-219 for DPNP requires additional protocol information but doesn't affect other studies.
- RAP-219 is being evaluated in ongoing trials for focal epilepsy and bipolar disorder, with promising initial safety data.
Rapport Therapeutics’ is actively recruiting patients for its phase 2a trial investigating its lead therapy candidate RAP-219 among patients with focal epilepsy, with topline data anticipated in mid-2025.
Abraham N. Ceesay
(Credit: Rapport)
According to a new announcement, the FDA has placed a clinical hold on Rapport Therapeutics’ submitted investigational new drug (IND) application for the initiation of a phase 2a proof-of-concept trial assessing RAP-219, an investigational therapy for epilepsy, as a potential treatment of patients with diabetic peripheral neuropathic pain (DPNP).1
The agency has requested the company to provide additional information and amendments specific to the protocol design of the trial. Rapport noted in the announcement that it believes in its ability to resolve this request and will offer an update on the expected timing of the phase 2a trial initiation once obtainable. This clinical hold is specific to the IND for DPNP and did not impact the company’s other studies assessing RAP-219, such as in the ongoing phase 2a trial for focal epilepsy or planned proof-of-concept trial for bipolar disorder.
"We are pleased with the progress we’re making with RAP-219, particularly as we continue the execution of our phase 2a proof-of-concept trial in focal epilepsy,” Abraham N. Ceesay, chief executive officer of Rapport, said in a statement.1 “The continued learnings from our ongoing clinical activities, including the MAD-2 and PET trials as well as our pharmaceutical development efforts, have only strengthened our confidence in the pipeline-in-a-product potential of RAP-219 as a potentially transformational treatment for focal epilepsy, peripheral neuropathic pain, and bipolar disorder.”
Rapport noted that it is performing a second multiple ascending dose trial (MAD-2) of RAP-219, which is anticipated to be completed in the fourth quarter of 2024. In this trial, the company will investigate additional dosing regimens specifically to inform dosing for its phase 2a trial for the treatment of patients with bipolar acute mania. The initial MAD trial showed that RAP-219 was generally well tolerated at target therapeutic exposures and had no serious adverse effects as well as no drug-related treatment-emergent adverse events above Grade 1.
The company also announced that its phase 1 human positron emission tomography (PET) trial in healthy adult volunteers is underway. The unique trial will use a companion PET radiotracer to validate brain target receptor occupancy and brain region specificity across a range of RAP-219 dosing and exposure levels. Rapport noted that both topline results from the MAD-2 and PET trials will be provided in the first quarter of 2025.
RAP-219 aims to selectively target TARPγ8, a receptor-associated protein which is associated with the neuronal α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, which is known as a clinically confirmed target for epilepsy. The company also noted that it continues to progress the development of a long-acting injectable formulation of RAP-219 as the first potential antiseizure medication in a depot formulation, which may offer a greater ease-of-use and better patient adherence.
Rapport’s phase 2a proof of concept trial of RAP-219 in focal epilepsy is also underway with patient recruitment and screening. The company noted that the trial is on track and expects topline results in mid-2025. This trial is enrolling adult patients with drug-resistant focal epilepsy who have an implanted responsive neurostimulation (RNS) device, which continually captures intracranial electroencephalography data and records the frequency of long episodes, and are demographically alike those expected in future registrational trials.
In September 2024, the company presented on the mechanism of action for RAP-219 as well as the design of the phase 2a proof-of-concept trial for focal epilepsy at the International League Against Epilepsy 15th Annual European Epilepsy Congress and the 2024 Epilepsy Foundation Pipeline Conference.2 Coming up at the 2024 Annual Epilepsy Society meeting held in December, the company will have 4 poster presentations focused on RAP-219, which will highlight preclinical data, SAD/MAD trial results, food effect data, and new analyses on the correlation between RNS-measured long episode and clinical seizure frequency in patients with refractory focal epilepsy.
