Recently Rapport Therapeutics announced that it had achieved positive results from its phase 2a RAP-219-FOS-201 clinical study. The point of this trial was to evaluate the use of this candidate to go after drug-resistant focal onset seizure patients. It is not just that there was noted to be a positive outcome, but that the main efficacy primary endpoint of change in frequency of RNS-reported long episodes (LEs). RNS is an implantable device that is used to determine brain activity and is also equipped to stop a seizure before it is going to happen. With that being said, this efficacy endpoint that was evaluated in a total of 27 patients was split up into two parts.
One part evaluated where a certain percentage achieved a ≥30% reduction in LEs from baseline, and the final outcome of this part of the efficacy endpoint was said to be that of 85.2%, with a statistically significant p-value of p<0.0001. The second part of this specific endpoint was just looking at the average reduction of long episode frequency from baseline and this was noted to be 71%, with a statistically significant p-value of p=0.0001.
This is only the beginning of what can be achieved with RAP-219, and I state this because it only deals with a short 8-week time frame. These patients are going to continue to be evaluated for another 8-week period, and it is highly likely that Rapport will offer a look at such longer-term data at a later time point. A focal onset seizure is a type of seizure that occurs in one specific hemisphere of the brain, although I will say that it can transverse to affect the other hemisphere as well. The type of symptoms that a patient experiences just honesty depend on what part of the brain is affected, and such symptoms can range from muscle issues, neurological problems or other bodily functions being altered.
With that being said, the company is looking to not specifically focus on the entire focal onset seizure patient population but instead a specific subset of patients who are resistant to currently available drugs. As Jacqueline French, M.D., principal investigator of the study, noted in the press release “Despite the available therapies, up to 40% of patients with focal epilepsy continue to experience seizures.” Thus, the point here is that the goal is not to attempt to conquer the entire focal onset seizure treatment space, but a specific aspect with an unmet medical need. In essence, to give these patients a new treatment option that is unique and unlike any other available therapy.
The key to RAP-219 is the company’s RAP technology, which stands for receptor-associated proteins or RAP. By targeting certain neuronal receptor complexes, the company can regulate receptor function and thereby modify disease state in specific disorders. The advantage of this technology is being able to go after targets that were not sought out beforehand because of complexity. The last item to note would be the precision to only go after certain RAPs in tissues of the person’s body, which provides a more narrow focus in drug targeting. The way that this AMPA receptor (AMPAR) negative allosteric modulator (NAM) provides the ability to help target these hard-to-treat disorders would be the selective nature of targeting it.
The point is instead of using RAP-219 to go after the entire AMPA receptors [AMPARs] system, there is a focus to focus solely on the RAP, which resides in certain portions of the brain. This is the targeted approach I was talking about beforehand. The point of specific targeting like this is to only go after where focal seizures begin. It remains to be seen, though, if the company is able to further establish proof of this in a phase 3 study, but there is a good chance after the data it just released from its phase 2a RAP-219-FOS-201 clinical study. Speaking of which, the intention is to initiate two phase 3 studies using RAP-219 to treat drug-resistant focal epilepsy patients in the third quarter of 2026. The end goal is to get these drug-resistant focal epilepsy patients to seizure freedom. What this entails is a hard feat, which is to prevent a patient from experiencing a seizure in roughly 12 months.
I want to state that this is only the beginning of what could be possible with the RAP technology that Rapport has. The reason why is because it noted that it is already in the process of evaluating this very same NAM in another trial. This is a phase 2 study using this drug candidate to treat patients with bipolar mania. The downside, though, is that investors likely won’t get to see clinical data from this mid-stage trial for quite some time, and that is since topline results from it are not anticipated until the first half of 2027.
Another expected milestone to keep an eye on from Rapport would be that of a program using RAP-219 to treat patients with diabetic peripheral neuropathic pain [DPNP], which is set to happen in 2025. This disorder is characterized as a painful condition found in patients with diabetes. Such patients suffer from high blood sugar levels, and while the impact of this is expanded throughout the body, one part of it that is greatly affected is the nerves. With the nerves being damaged, it leads to the painful events for these patients. The reason for an update being needed for this program is because the company is shifting through a problem it had with a clinical hold being placed on the IND to initiate a phase 2 study. At that time, the FDA requested additional information about such a trial. It remains to be seen if the company is able to overcome this hurdle with the FDA and get this program off the ground.