Phase 2 Dose-Finding Study of Intranasal Epinephrine Powder (NS002) Supports Development for Regulatory Submission
Nasus Pharma says promising phase 2 results for FMXIN002 show statistically significantly faster absorption than traditional autoinjectors and are published in global journal.
Nasus Pharma’s phase 2 clinical study of its investigational intranasal epinephrine powder for treatment of anaphylaxis, FMXIN002 (aka NS002), has been published in The Journal of Allergy and Clinical Immunology: Global, according to a June 3 company announcement.1 The study, conducted at Hadassah Medical Center in Jerusalem, compared the bioequivalence of 2 doses of FMXIN002 (3.6 mg and 4.0 mg) to the standard 0.3 mg intramuscular (IM) epinephrine autoinjector, EpiPen, in 12 healthy adult volunteers. The 4.0 mg dose demonstrated more rapid absorption and higher early plasma epinephrine levels than the IM comparator, according to the findings.2
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In the open label single-dose 3-treatment randomized, crossover study participants received single doses of 3.6 mg or 4.0 mg FMXIN002, as well as a standard 0.3 mg EpiPen. The study's primary objective was to identify an optimal nasal dose of NS002 that achieves adequate plasma epinephrine levels within the limited therapeutic window required for effective treatment of anaphylaxis.
Absorption of the 4.0 mg dose of FMXIN002 was significantly faster and more efficient than the autoinjector. Compared to the reference EpiPen, the 4 mg dose of NS002 demonstrated higher mean Cmax, and higher mean area under the curve (AUC) during the first 30 minutes after treatment compared, according to the study results. AUC for the first 4 minutes following administration was 4.7-fold higher following FMXIN002 4.0 vs EpiPen, a difference that reached statistical significance despite the small sample size, the authors wrote. FMXIN002 4.0 mg also showed a shorter median Tmax and T100 pg/mL than EpiPen. The total exposure over 2 hours was comparable to that of EpiPen.
Ten of the 12 4 mg-treated participants (91%) had reached the hemodynamic threshold of 100 pg/mL plasma epinephrine during the first 6 minutes following administration compared to just 55% after intramuscular injection. Ten minutes after administration, 81% of participants treated with FMXIN002 4.0 mg and 58% of those who received the 3.6 mg dose achieved plasma epinephrine of 200 pg/mL or greater compared with 67% of those treated with EpiPen who failed to reach 200 pg/mL. All adverse events were mild, transient, and self-resolving, and no serious adverse events occurred.
"This study demonstrates that FMXIN002 (NS002) intranasal epinephrine powder could enable faster and higher absorption of epinephrine into the plasma during the short therapeutic window required for the treatment of anaphylaxis," said Prof. Yuval Tal, head of the allergy and clinical immunology clinic at Hadassah Medical Center. "I have followed the development of NS002 since its first in-human study and am excited about its potential as a simple, convenient, needle free alternative to IM epinephrine." Among the benefits of NS002 Tal points to a shelf life of greater than 5 years and to the product's portability that could allow easily carrying multiple doses.
"By addressing the limitations of current treatments, this innovation could have the potential to significantly improve accessibility and adherence, ultimately saving lives in emergency situations."
FMXIN002 was developed based on Nasus Pharma’s proprietary powder-based intranasal platform. The product is delivered via a single-use Unidose device manufactured by Aptar Pharma. The formulation demonstrated robust chemical stability across all tested conditions, including 5 years at room temperature without humidity control, potentially offering a logistical and clinical advantage over liquid epinephrine autoinjectors, which degrade more quickly and often require temperature-controlled storage.
Based on the study findings the company plans to continue development of the 4 mg dose for regulatory submission.
