DCCR Tablets Reduce Body Fat in Prader-Willi Patients, Phase 2 Trial Shows

DCCR Tablets Reduce Body Fat in Prader-Willi Patients, Phase 2 Trial Shows

Treatment with Soleno Therapeutics’ diazoxide choline controlled release (DCCR) tablets reduced excessive appetite and lowered body fat in Prader-Willi syndrome (PWS) patients in a Phase 2 trial, the company announced.

The latest findings were presented during the Obesity Society Meeting 2018 in Nashville, Tennessee, in the poster, “Agonizing the KATP Channel with DCCR Results in Fat Loss in Prader-Willi Syndrome Patients.

PWS is characterized by growth hormone deficiency, behavioral disturbances, and an insatiable hunger — called hyperphagia — that leads to excessive eating and life-threatening obesity.

It is believed that the excessive appetite in PWS patients is caused by the release of two neurotransmitters — the neuropeptide Y (NPY) and agouti-related protein (AgRP) — by certain nerve cells.

DCCR, an oral, extended-release formulation of diazoxide, works by activating potassium channels in these neurons, inhibiting the release of NPY and AgRP. The candidate has already shown promise in addressing excessive hunger and other PWS symptoms, including aggressive/destructive behaviors, increased fat mass, and abnormal fat profiles.

“By addressing both hyperphagia and the underlying metabolic disease manifestations, DCCR has the potential to provide a treatment option for patients that will simplify disease management and improve quality of life, particularly as DCCR is suitable for once-daily oral dosing,” Jennifer Miller, MD, associate professor at the University of Florida College of Medicine and senior author of the study, said in a press release.

The PC025 Phase 1/2 trial (NCT02034071) enrolled 13 patients, 10 to 22 years old, with genetically confirmed PWS.

Participants received increasing DCCR doses, starting at 1.5 mg/kg and increasing every two weeks through four dose levels up to 4.2 mg/kg, and then were treated with a stable dose for an additional four weeks.

The 11 patients who completed the 10-week treatment experienced a significant reduction (mean 3.8%) in their total body fat after DCCR treatment. The reduction was particularly seen in visceral, or belly, fat, as these patients experienced a significant reduction in their waist circumference (mean 3.45 cm), but no changes in leg, arms, or trunk fat.

The greater effect on fat mass was seen among patients receiving the highest dose, who reported a 6.1% reduction in their total body fat mass. They also lost more fat in their trunk, legs, and arms, but the results did not reach statistical significance.

Overall, patients receiving the 4.2 mg/kg dose lost 3.3 times more belly fat than the overall population, and 4.1 times more fat in their legs.

“These data provide further clinical evidence that DCCR has the potential to treat both the behavioral and cardiometabolic symptoms that challenge PWS patients,” said Anish Bhatnagar, MD, CEO of Soleno. “We are encouraged by these significant impacts on body fat and continue to advance our ongoing DESTINY PWS Phase 3 trial.”

DESTINY (NCT03440814), a randomized, placebo-controlled Phase 3 trial, aims to evaluate the effects of DCCR versus a placebo in PWS patients age 4 and older. The study is still enrolling in the U.S. and is expected to include 105 participants.

DCCR has received orphan drug designation for the treatment of PWS in the United States and in Europe, and fast track status in the U.S, which is expected to support its clinical development and  expedite its review and approval.