Avadel’s Once-Nightly Narcolepsy Drug Hits Three Co-Primary Endpoints In Late-Stage Trial

Dublin, Ireland-based Avadel Pharma announced positive topline data from its pivotal Phase III REST-ON clinical trial of FT218 for excessive daytime sleepiness and cataplexy in patients with narcolepsy. Company shares rocketed 30% in premarket trading in response to the news.

The trial, under a Special Protocol Assessment, met all three co-primary endpoints at all three doses, 9g, 7.5g, and 6g. The endpoints were Maintenance of Wakefulness Test (MWT), Clinical Global Impression-Improvement (CG-I) and mean weekly cataplexy attacks. Cataplexy is a sudden and uncontrollable muscle weakness or paralysis that is sometimes triggered by a strong emotion, such as laughter.

“We are excited to see these positive topline data from the REST-ON study, where all three dose levels of once-nightly FT218 demonstrated a statistically significant and clinically meaningful improvement on the measures of the two prominent symptoms of narcolepsy, as well as an improvement in overall functioning compared to placebo,” said Jordan Dubow, chief medical officer of Avadel.

Dubow added, “Once-nightly FT218 delivered a clinically meaningful response within three weeks of treatment initiation, which was sustained through each treatment period. Commonly known sodium oxybate adverse reactions occurred at low rates at the highest dose level. We think once-nightly FT218, if approved, has the potential to be a meaningful contributor to patient care.”

The REST-ON study evaluated 212 patients. The 9g dose showed a highly significant and clinically meaningful improvement compared to placebo across all three endpoints. The dosage was generally well-tolerated. The most common adverse reactions occurred at low frequency, which were nausea, vomiting, decreased appetite, dizziness, somnolence, tremor and enuresisb (bed-wetting). The discontinuation rate at the 9g dose for adverse reactions was 3.9%.

After the 9g dosing was analyzed, the 7.5g and 6g doses were analyzed, which also showed highly statistically significant clinical meaningful improvement compared to placebo.

FT218 is an investigational, once-nightly formulation of Micropump controlled-release sodium oxybate. The drug was granted Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for narcolepsy. A twice-nightly formulation is already approved by the FDA for the same indication, but the Orphan Drug Designation was granted on the possibility FT218 would be clinically superior and might be safer.

“The successful outcome of the REST-ON study strengthens our belief that, if approved, once-nightly FT218 has the potential to be a significant advancement for patients in the estimated $1.7 billion twice-nightly sodium oxybate market,” said Greg Divis, Avadel’s chief executive officer.

He went on to say, “Our proprietary market research with physicians and patients informs us that there is a strong interest in a once-nightly sodium oxybate formulation. We look forward to sharing the results from the REST-ON study with the FDA and progressing toward a potential approval that would allow us to bring this important treatment to the patients who need it most. If approved, FT218 would be the first once-nightly therapy to address both excessive daytime sleepiness and cataplexy in patients with narcolepsy. We extend our appreciation to the patients, investigators, study staff, and advocacy groups who contributed to the REST-ON Phase III study and supported the development of this potentially life-changing treatment.”-Bio Space