CAMP4 advances rare disease treatment for SYNGAP1 into human trials

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Regulators in Australia are providing hope to thousands of patients around the world that suffer from a rare genetic disease that currently has no approved treatment.

Late last month, CAMP4 Therapeutics was given permission by Australia’s top drug regulator to initiate a clinical trial for its therapy designed to treat SYNGAP1-related disorders, a rare genetic disease marked by epilepsy and neurodevelopmental delays. The trial, which will be designed to test the safety, efficacy and dosing of the the drug, mark the first time the antisense oligonucleotide treatment, or ASO, will be used in people, and represents a major milestone for patients that suffer from SYNGAP1.

SynGAP is a protein crucial to brain development. It helps with learning and memory, and also with regulating communication in the synapses of the brain. Patients with SYNGAP1 suffer from a genetic mutation that causes their brain to receive less of the SynGAP protein.

And while just over 1,800 SYNGAP1 patients have been identified globally, researchers believe that number is much higher. Mutations in the SYNGAP1 gene are surprisingly common and are estimated to account for between 1%-2% of all intellectual disabilities.

Early results for CAMP4’s ASO therapy have been promising. A preclinical study involving primates found the treatment increased protein expression in the brain, and a mouse model showed improved seizure measures.

CNBC Cures’ Becky Quick – whose daughter Kaylie was diagnosed with SYNGAP1 at age 2 – spoke with CAMP4’s CEO, Josh Mandel-Brehm, and asked him about the trial’s design and what it means for the thousands living with the devastating rare disease.

Mandel-Brehm said that while the ultimate hope is for a cure, researchers will use the study to measure any sign of improvement from trial participants. “From speaking with parents and listening to their stories, success can be from one parent lowering seizures, from another just hearing your daughter or son speak to allowing your guard to go down for a moment, so your child doesn’t lope into endanger. It it’s different for everybody.” Mandel-Brehm added, “We’re not going to set a definition for success because we’re going to let the data guide us.”

CAMP4, which also received approval from Argentinian regulators to initiate a trial in that country, hopes to include at least 30 SYNGAP1 patients across multiple locations. The initial trial is designed to treat children between 2-18 years old, though Mandel-Brehm says the strategy is to try and target younger patients first.

CAMP4’s trial will deploy a double-blind model, in which half the participants receiving the ASO – a process that involves a lumbar puncture to inject the medication directly into the cerebrospinal fluid – will be given a placebo. Administering placebos in clinical trials involving rare disease patients is sometimes seen as a controversial practice within that community, where patients who desperately need therapies often have very few approved treatment options. Advocacy groups have followed the issue particularly closely in the U.S., where regulators at the FDA have made headlines over their recent scrutiny of clinical trials in the rare disease space that did not include the use of placebos.

Mandel-Brehm said he believes using the double-blind approach will more quickly get regulators the data they need in order to approve the new ASO. “Different regulatory agencies have different bars,” Mandel-Brehm said. “Ultimately the goal is not just to show the drug works, it’s to get it on the market to help patients.”

He added that the trial is being designed so that patients receiving a placebo will be able to transition over to the drug if early results indicate a positive result from the therapy.

“We’re not asking patients to only get a control and nothing else,” Mandel-Brehm said. “There’s a balancing act here because we also want to do something ethically correct for these patients that are agreeing to enter the study.”

While CAMP4 has not announced plans to initiate a trial in the U.S., Mandel-Brehm said his company is currently planning on having those conversations with U.S. regulators. The company plans to initiate the trial in the fourth quarter and treat patients throughout 2027.

Mandel-Brehm said more details will be announced at CAMP4’s investor relations day on Monday, September 28.