NLS Pharmaceutics Ltd. announced the final results from its Open Label Extension (OLE) Study for Quilience® (Mazindol ER) in the treatment of narcolepsy. The OLE study offered patients completing the 4-week randomized, double blind (DB) Phase 2 trial for Mazindol ER the option to receive the drug candidate, Mazindol ER, for an additional 6 months as a once-daily, monotherapy on an open-label basis. Of the 60 patients who completed the randomized controlled DB Phase 2 trial, 87% of patients (N=52) elected to enroll into the OLE study.

The most frequent (>5%) adverse events reported were dry mouth, COVID-19, constipation, urinary tract infection and nausea, and there were no serious adverse events related to study medication. This 6-month OLE study of Mazindol ER, a first in class, unique dual mechanism of action pan-monoamine reuptake inhibitor and orexin-2 partial receptor agonist, showed that patients treated with Mazindol ER in the randomized Phase 2 trial (DB) saw an additional improvement of 0.8 (SD=2.86) points in excessive daytime sleepiness (EDS) on the Epworth Sleepiness Scale (ESS). At the conclusion of the OLE, the mean ESS score for these patients reached 8.9 (SD=6.12), with lower scores denoting an improvement in the condition (improved wakefulness).

Of note, ESS scores of 10 or below are considered typical scores for subjects without narcolepsy. As previously concluded in the interim analysis of the OLE reported in September 2022, these data indicate that maximum efficacy on ESS with Mazindol ER is reached at approximately 2 months of treatment, and these scores were subsequently maintained throughout the 6-month OLE duration. Overall, the mean ESS score for these patients declined by approximately 10.2 (SD=5.83) points from their DB study baseline to month 6 in the OLE.

Similarly, patients receiving placebo in the DB Phase 2 trial who rolled over to receive Mazindol ER in the OLE study, saw an improvement in ESS scores, declining to levels comparable to those treated with Mazindol ER in both the DB and OLE trials. This effect was maintained through the 6-month OLE study, with ESS scores similar to the DB Mazindol ER group. Patients with Narcolepsy Type 1 (NT1), treated with Mazindol ER in the randomized Phase 2 trial, experienced a mean number of weekly cataplexy episodes of approximately 2.9 (SD=4.30) at the end of the 4-week DB period, down from a baseline level of approximately 16.6 (SD=10.96) at the beginning of the trial.

During the 6-month OLE study, mean weekly cataplexy episodes for these patients remained relatively stable in the 2 to 4 range through week 24. For NT1 patients with cataplexy receiving placebo in the DB Phase 2 trial, the mean number of weekly cataplexy episodes was approximately 10.3 (SD=12.11) at the end of the 4-week double-blind period. During the 6-month OLE study, when treated with Mazindol ER, these patients caught up to previously treated patients, achieving mean weekly cataplexy episodes of 3.8 (SD=7.05) at 8 weeks of treatment.

This favorable effect was maintained for these patients in the 2-4 episodes per week range throughout the 6-month OLE study. For both groups, the mean reduction in weekly cataplexy episodes was more than 80% from the DB study baseline. Notably, there were patients diagnosed with Narcolepsy Type 1 who achieved zero weekly cataplexy episodes in the OLE study, with some of those maintaining this effect through week 24.

For example, the graphs below show the results of a 23 year-old female with NT1 who received Mazindol ER in both the DB and OLE study periods.