Eagle Pharmaceuticals, Inc. ("Eagle" or "the Company") (Nasdaq:EGRX) today announced completion of enrollment of the Company's second clinical study to further evaluate the safety and efficacy of RYANODEX® (dantrolene sodium for injectable suspension) for the treatment of exertional heat stroke ("EHS"), an investigational new indication for the product.
The randomized and double-blinded study was conducted at four Emergency Departments in the Makkah region of Saudi Arabia during the 2018 Hajj Season, which took place August 19-24, 2018. The study enrolled seven severely ill EHS patients. Based on a preliminary analysis of the data, EHS patients who received RYANODEX plus Standard of Care ("SOC"), which consists of body cooling by physical methods and supportive measures, showed an additive benefit compared to patients receiving cooling only.
The two treatment groups had comparable baseline characteristics, including severe hyperthermia and severe neurological dysfunction. Patients randomized to Group A (RYANODEX plus SOC) had a mean baseline core body temperature of 107.8 °F and mean Glasgow Coma Scale (GCS) score of 5. Similarly, patients in Group B (SOC only) had a mean core body temperature of 107.2 °F and mean GCS score of 5 at baseline. A GCS score of 5 represents severe brain injury.
Preliminary evaluation of the data show that of the four patients dosed with RYANODEX, two had restoration of neurological functioning, and another patient showed substantial improvement over the course of the study. The fourth patient, who had an initial core body temperature of 112.1 °F, remained unchanged. In contrast, the SOC group had three patients. One patient had restoration of neurological functioning, one remained with severe impairment and one subject showed further deterioration of neurological functioning.
This preliminary assessment is consistent with the data from the study conducted in 2015, in which patients dosed with RYANODEX plus SOC showed an additive benefit compared to patients receiving SOC only.
During the 2018 Hajj, overall emergency room visits were dramatically decreased from previous years due to well-implemented crowd management, lower temperatures, lower humidity and other external factors. As a result, the number of EHS patients available for study enrollment was also significantly less than in previous years, and therefore much lower than anticipated. The Company intends to complete the analysis of the data and meet with the U.S. Food and Drug Administration ("FDA") to discuss next steps.
"Our preliminary evaluation of the data indicates that the patients receiving RYANODEX showed an improved outcome compared to patients treated with cooling only. We have now conducted two randomized, controlled studies and have obtained comparable results in both studies. We have 41 subjects for a rare disease with FDA fast-track and Orphan Drug designations, and no other approved drugs to treat EHS," stated Scott Tarriff, Chief Executive Officer.
"Based upon the collective results of our two clinical trials as well as other work performed by the Company and researchers around the world, we believe there is sufficient data to provide evidence of safety and efficacy for the use of RYANODEX for the treatment of EHS. We plan to meet with the FDA to discuss the next steps in making this very important product available to those afflicted with exertional heat stroke," concluded Tarriff.
This study was conducted in compliance with all current FDA regulations and is the second trial conducted by Eagle. The study intended to provide confirmatory evidence of the Company's initial safety and efficacy study of RYANODEX for EHS conducted in September 2015 and to satisfy the FDA's requirements to amend Eagle's original NDA.
Additional details about the study can be found at www.ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT03600376).
Results of 2015 Study
Eagle's initial study was conducted from September 22-27, 2015, at the Emergency Departments of four hospitals during the Hajj pilgrimage in the Makkah region, Saudi Arabia.
The open-label, randomized, 2-arm study was primarily designed to assess the change in the level of neurological impairment in subjects suffering from the symptoms of EHS, from baseline to 90 minutes post-randomization, using the Glasgow Coma Scale ("GCS").
The use of a validated and well-known instrument to evaluate neurological functioning, such as the Glasgow Coma Scale, provides a reliable assessment of CNS impairment and its progression over time.
The study enrolled 34 EHS patients between 18-45 years of age.
Subjects were randomized 1:1 into two groups to receive either RYANODEX plus SOC, (Group A, n=17), or SOC alone (Group B, n=17).
Per study protocol, all subjects experienced exertional physical activity within the previous 24 hours, and demonstrated hallmark clinical features of EHS, including:
- Presence of neurological impairment, evaluated using the Glasgow Coma Scale ("GCS");
- Baseline core body temperature of 104° F (40° C) or greater; and,
- Tachycardia (at least 100 heart beats per minute)
Baseline disease characteristics were comparable between the two groups, including a mean GCS score (Group A: 6.1 vs. Group B: 5.9) representing severe neurological impairment, and severe hyperthermia (Group A: 106.5° F (41.4° C) vs. Group B: 106.7° F (41.5° C).
Patients were evaluated at baseline and at regular time intervals post-randomization for changes in level of consciousness using GCS, and core body temperature.
Study results showed that a greater proportion of patients treated with Ryanodex plus SOC exhibited a clinically meaningful improvement in their neurological functioning (GCS ≥ 13) within 90 minutes (29.4%) and within 24 hours post-randomization (47.1%), compared with SOC only-treated subjects (11.8% and 23.5%, respectively).
In addition, pre-specified odds ratio analysis showed that odds of achieving a GCS score ≥ 13 within 90 minutes postrandomization was about 3 times greater for subjects in the Ryanodex plus SOC group than for subjects who received SOC-only and remained almost unchanged at or prior to 24 hours postrandomization. Also, the median time to reach first rectal temperature ≤ 38°C was shorter in the Ryanodex plus SOC group (90.0 minutes) than in the SOC only group (103.0 minutes).
Overall, safety findings were comparable between the two study groups, and there were no serious drug-related adverse events. Fewer patients experienced treatment-emergent adverse events in Group A (64.7%), as compared to Group B (76.5%), and the incidence of serious adverse events in each of the two treatment arms was comparable. In summary, the safety results of the study are consistent with the known, and well characterized, safety profile of RYANODEX.