Full Press Release Details
NLS Pharmaceutics Announces Positive Interim
Top-Line Data for Quilience (Mazindol ER) in Patients with Narcolepsy
Switzerland/Zurich, March 16, 2022 - NLS
Pharmaceutics Ltd. (Nasdaq: NLSP, NLSPW) ("NLS" or the "Company"), a Swiss clinical-stage biopharmaceutical company
focused on the discovery and development of innovative therapies for patients with rare and complex central nervous system disorders,
announces positive interim top-line data from its Phase 2a clinical trial evaluating its lead product candidate, Quilience (Mazindol
ER), in the treatment of narcolepsy. The data are being presented and discussed today during a symposium sponsored by NLS at the World
Sleep Congress (World Sleep 2022), being held in Rome, Italy.
Quilience (Mazindol ER) Interim Efficacy Data
Of the 60 patients targeted for full enrollment
in the U.S. Phase 2a trial (Study NLS-1021), 27 were randomized and completed the study for the interim analysis. The interim analysis
database included 13 patients on treatment and 14 patients on placebo, with balanced mean baseline Epworth Sleepiness Scale (ESS) scores
(18.6 +/-2.81 for treatment and 18.0 +/-2.72 for placebo). All patients enrolled in the interim analysis were utilizing combination therapy
before the trial's wash out period, with the majority of participants on stimulant or wake-promoting agents to treat their excessive
daytime sleepiness (EDS). Approximately one-third of patients enrolled in the interim analysis were diagnosed with narcolepsy type 1 (NT1)
and suffer from both EDS and cataplexy symptoms. Eligible NT1 patients must have moderate to severe disease according to the study protocol
- defined as having more than 3-4 cataplexy attacks per week. Study participants on treatment are required to undergo a 1-2-week wash
out period (depending on prior therapy). After the wash out period, participants are randomized to receive either once-daily treatment
with Mazindol ER 2mg for week 1 and 3mg for weeks 2-4, or placebo for 4 weeks.
For EDS, the trial's primary endpoint, patients
on Mazindol ER exhibited a mean decrease of 7.3 points on the ESS compared to a 3.0 point decrease for patients on placebo. Patients on
Mazindol ER showed a mean 39% improvement on ESS from baseline. The placebo-adjusted reduction of 4.3 points is deemed to be clinically
meaningful and is competitive compared to current narcolepsy treatments, despite the short duration and relatively small number of patients
in the interim analysis. These interim results confirm the statistical power of the ongoing Phase 2a trial, which will continue as planned.
In the figure below, a rapid onset of action is
observed for Mazindol ER, with treated patients exhibiting consistent and sustained EDS improvement over the 4-week treatment period.
The placebo effect in the interim analysis exhibits stabilization after week 3, consistent with other narcolepsy therapeutic clinical
Epworth Sleepiness Scale (ESS) Total Score: Change from Baseline
to Last Visit (ITT Population)
Quilience (Mazindol ER) Phase 2a Interim Safety/Tolerability
To date, Mazindol ER was generally safe and well-tolerated
in the current Phase 2a trial, and the interim data are consistent with prior mazindol studies, including the Company's trials evaluating
treatment of attention deficit hyperactive disorder (ADHD). No patients dropped out of the study due to safety or efficacy concerns, and
only one patient in the interim analysis discontinued the study for personal reasons. This compares favorably to other clinical trials
for narcolepsy treatments, for which study discontinuation rates can be as high as 15% or more for efficacy and safety reasons.3
No serious adverse events were reported in the interim analysis and all reported adverse events were mild or moderate and resolved immediately
with no intervention required.
"These interim data are very encouraging
and demonstrate the potential for Mazindol ER to address the core symptoms of narcolepsy with a rapid onset of action and a favorable
safety and tolerability profile," said Bruce Corser, M.D., Medical Director at the Cincinnati-based
Sleep Management Institute and a clinical investigator in the NLS-1021 trial. "Mazindol's dual mechanism of action
as a partial orexin agonist and pan-monoaminergic reuptake inhibitor distinguishes this therapeutic candidate and is of particular interest
in the field given the drug's potential to treat narcolepsy at its root cause. I am looking forward to the final results from this
trial and the potential to utilize this novel therapy in more of my patients."
Quilience (Mazindol ER) Open Label Extension
Study NLS-1022 (OLE study) enables patients completing
the randomized controlled trial to access treatment with Mazindol ER without any background stimulant and or anti-cataplexy treatment
for up to 6 months. As of the data collection date for the Phase 2a interim analysis (February 25, 2022), 82% of patients who completed
the randomized controlled study elected to participate in the OLE study. A majority of those patients remain in the OLE study and on treatment
with Mazindol ER, including participants suffering from NT1, with one patient on single agent therapy for over 3 months.
"We are extremely pleased with these interim
results, which offer the first evidence from a prospective randomized clinical trial that Mazindol ER has the potential to become a disruptive
treatment for narcolepsy," said Alex Zwyer, Chief Executive Officer of NLS Pharmaceutics. "I am very proud of the NLS clinical
team's execution and thankful for our clinical sites who are recruiting participants at among the fastest pace in the industry as
we focus on bringing this important treatment to patients as soon as possible. Importantly, we are seeing strong participation from NT1
patients in this trial. Given that the interim results are in-line with the documented historical utility of mazindol in treatment-resistant
narcolepsy patients under compassionate use, we are confident that our proprietary Mazindol ER formulation will prove to be a safe and
effective therapy that can address a broad spectrum of narcolepsy symptoms."
"These interim results have exceeded on
our expectations with regard to the beneficial effects of Mazindol ER's unique mechanism of action and validate the body of retrospective
evidence that support the compound's efficacy and safety in the treatment of narcolepsy," said Eric Konofal, PhD, MD Chief
Scientific Officer of NLS Pharmaceutics. "The rapid onset of action and large effect size between treatment and placebo are superb
in this dataset and are consistent with the results that we generated in our two ADHD trials, in addition to affirming Mazindol ER's
benign safety and tolerability profile. Mazindol is thought to address a wide spectrum of narcolepsy symptoms including EDS, cataplexy,
sleep paralysis, and nocturnal hallucinations, and we are excited to obtain the final Phase 2a results to fully understand the drug's
therapeutic potential, and to move this product candidate into advanced clinical trials."
About World Sleep 2022
The international Congress of the World Sleep
Society is the most important meeting of Sleep Research Scientists worldwide. Now in its 16th iteration, the World Sleep Congress consistently
gathers the best minds in sleep medicine and research for multiple days of scientific sessions and networking. World Sleep 2022 will be
held in Rome, Italy, March 11-16, 2022, with fourteen keynote speakers selected to represent a broad range of sleep medicine
and research. Twenty-two sleep medicine and research courses are in development, and attendees will have access to presentations
by world-class researchers in chrono-medicine, narcolepsy, sleep surgery, insomnia, sleep-focused basic research, and more. A truly
global meeting, 77 countries were represented at World Sleep 2019 which featured 89 symposia, 192 oral abstracts, and over 1,100 poster
presentations. World Sleep 2022 presents a unique opportunity for sleep medicine professionals no matter their specialty or career stage.
About NLS Pharmaceutics
Pharmaceutics Ltd. is a Swiss clinical-stage biopharmaceutical company led by an experienced management team with a track record of developing
and repurposing product candidates to treat rare and complex central nervous system disorders. The Company's lead product candidate, Quilience,
is a proprietary extended-release formulation of mazindol (mazindol ER) and is being developed for the treatment of narcolepsy, and potentially
other sleep-wake disorders such as idiopathic hypersomnia. Mazindol is a triple monoamine reuptake inhibitor and partial orexin-2 receptor
agonist, which was used for many years to treat patients diagnosed with narcolepsy in compassionate use programs. A Phase 2a clinical
trial evaluating Quilience in adult subjects suffering from narcolepsy is currently ongoing in the United States. Previously, NLS successfully
completed a phase 2 study in the U.S. evaluating Nolazol (mazindol
controlled-release) in adult subjects suffering from ADHD. The study met all primary and secondary endpoints and Nolazol
was well-tolerated. Quilience has received Orphan Drug Designations both in the
U.S. and in Europe for the treatment of narcolepsy. Up to 1/3 of narcoleptic patients are also diagnosed with ADHD.
Safe Harbor Statement
This press release contains
express or implied forward-looking statements pursuant to U.S. Federal securities laws. For example, NLS is using forward-looking statements
when it discusses that the interim results confirm the power of the ongoing Phase 2a trial and demonstrate
the potential for Mazindol ER, that the trial will continue as planned, that Mazindol ER has the potential to be used in more patients
and be a disruptive treatment for narcolepsy, the belief that the interim clinical trial results confirm the beneficial effects of Mazindol
ER's unique mechanism of action and validate the body of retrospective evidence that support the compound's efficacy and safety
in the treatment of narcolepsy, the confidence that its Mazindol ER formulation will prove to be a safe and effective therapy that
can address a broad spectrum of narcolepsy symptoms and the timing of the final results of the trial.
These forward-looking statements and their implications are based on the current expectations of the management of NLS only, and are subject
to a number of factors and uncertainties that could cause actual results to differ materially from those described in the forward-looking
statements. The following factors, among others, could cause actual results to differ materially from those described in the forward-looking
statements: changes in technology and market requirements; NLS may encounter delays or obstacles in launching and/or successfully completing
its clinical trials; NLS' products may not be approved by regulatory agencies, NLS' technology may not be validated as it progresses further