First FDA-Approved Drug for Rare Childhood Obesity-Related Metabolic Disease

Prader-Willi syndrome is a rare genetic disorder that has posed significant challenges in the field of obesity management due to its complex nature. This condition leads to excessive and insatiable hunger, often forcing affected individuals and their families to take extreme measures to control food consumption, such as locking away food sources. Despite being recognized in medical literature for decades, effective treatment options have remained elusive until the recent approval of a new drug.

The newly FDA-approved drug, Vykat XR, developed by Soleno Therapeutics, marks a milestone in the treatment of this condition. The drug specifically targets hyperphagia, the intense hunger experienced by Prader-Willi patients, and is approved for use in individuals aged four and older. Prader-Willi syndrome is named after Swiss physicians who first documented it in 1956. It arises when certain genes responsible for regulating hunger are not expressed adequately, leading to persistent feelings of starvation regardless of actual food intake. This condition significantly increases the risk of cardiometabolic issues and other obesity-related complications.

Soleno Therapeutics, based in Redwood City, California, has been at the forefront of developing treatments for Prader-Willi syndrome, a disorder affecting an estimated 300,000 to 400,000 people worldwide. While symptoms often begin to manifest around ages seven or eight, they can appear earlier. The company's CEO, Anish Bhatnagar, highlighted the debilitating nature of hyperphagia during a recent conference call, explaining how it feels like the brain is falsely signaling starvation despite food being consumed.

Vykat's active ingredient, diazoxide choline, has been used in other medical contexts for over five decades, particularly for managing hypoglycemia due to hyperinsulinism. Traditionally, diazoxide is available as an oral suspension under the name Proglycem, produced by Teva Pharmaceutical. Soleno's innovation lies in formulating diazoxide choline into an extended-release tablet, offering the benefit of once-daily dosing by ensuring gradual release and lower blood concentration peaks compared to the existing generic version.

The mechanism through which Vykat addresses hyperphagia in Prader-Willi patients is not entirely understood. However, it is known that diazoxide choline influences potassium channels, crucial for various physiological functions, which may include appetite regulation. By targeting these channels in areas like the brain, pancreas, and adipose tissue, Vykat has the potential to temper food cravings and decrease body fat accumulation, thereby preventing the onset of insulin resistance.

Soleno's journey toward FDA approval was not straightforward. Initial trials did not demonstrate significant changes in hyperphagia. However, a thorough analysis of data collected preceding the Covid-19 pandemic revealed meaningful improvements, leading to adjustments in the study protocol with FDA approval. This involved focusing on patients from an open-label extension study, where participants who switched from Vykat to placebo experienced notable worsening of hyperphagia.

Historically, drug research for Prader-Willi has faced hurdles. Previous attempts by companies like Zafgen and Millendo Therapeutics were abandoned due to clinical trial failures. Other firms are exploring different avenues, such as Aardvark Therapeutics, which is conducting a Phase 3 trial on a drug designed to engage TAS2 receptors in the gut to suppress hunger hormones.

Soleno plans to launch Vykat in April, with dosage tailored to patient weight, available in three strengths. The pricing strategy anticipates initial adoption primarily among children and young adults, potentially lowering costs relative to the trial's average patient weight. Efforts are underway to ensure comprehensive insurance coverage, with expectations for requiring prior authorization and genetic confirmation due to the drug's rare disease classification.

International expansion is also on the horizon, with plans for a European regulatory submission. While diazoxide is available as a generic drug, Soleno cautions against substituting it for Vykat due to different pharmacokinetic profiles. The company underscores these distinctions to ensure patients receive the specific benefits of Vykat, strengthening its position as a pioneering step in Prader-Willi syndrome treatment.