Initial topline Olinvyk data from patient real-world clinical outcomes study

The VOLITION study (n=203 patients), a real-world, open-label, multi-site study, assessed the potential impact of Olinvyk on respiratory, gastrointestinal (GI), and cognitive function outcomes in the postoperative setting, and was led by clinical outcomes research experts from the Cleveland Clinic and the Wake Forest Baptist Health Medical Center. Initial GI and cognition data are available, with respiratory outcome data expected mid-2023.

The ARTEMIS study was an electronic medical records (EMR) based assessment focused on clinical and health resource utilization outcomes. The study reviewed Olinvyk- treated patients in the VOLITION study with comparable surgical patients treated with other IV opioids, at the same institutions and during the same general time period. Initial ARTEMIS data from Wake Forest Baptist Health is currently available, representing 96 Olinvyk -treated patients and 457 matched patients treated with other IV opioids.

VOLITION Preliminary Topline Results (n=203) : GI Complete Responder Rate (prespecified exploratory endpoint). 52.2% of Olinvyk-treated patients were classified as GI complete responders, defined as no vomiting and no antiemetic use throughout the postoperative period. As reference, in pooled data for the Company’s pivotal Phase III studies of Olinvyk, the GI complete response rate was 46.2% (0.35mg) and 39.7% (0.5mg). As reflected in the Olinvyk label, nausea and vomiting were two of the most common adverse events reported in the controlled clinical trials. Wakefulness / Sedation, (prespecified exploratory endpoint). Over 90% of Olinvyk-treated patients reported feeling “alert and calm” from the morning of the first post-operative day and at every observation point thereafter, based on the Richmond Agitation-Sedation Scale. Sedation is an established risk of opioids including Olinvyk. Cognition (prespecified exploratory endpoint). Only 3.9% of Olinvyk-treated patients exhibited symptoms suggesting delirium at any point in the 48-hour post-operative period. Symptoms suggestive of delirium were assessed based on the validated 3D-CAM screening tool. Data from Primary, Secondary and Other Exploratory Endpoints. Data is not yet available for other endpoints, including the primary and secondary respiratory endpoints, as well as other prespecified exploratory endpoints. The Company expects to report these data mid-2023. Tolerability; No drug-related serious adverse events (SAEs) and no deaths were reported in the VOLITION study. Data on other adverse events is not yet available, and the Company expects to report these data mid-2023.

ARTEMIS (EMR-Based) Initial Results from Wake Forest Baptist Health Healthcare Utilization Measures. Olinvyk-treated patients had a statistically significant 1.6 day (~27%) reduction in average overall hospital length of stay compared to matched patients treated with other IV opioids (P=0.0001), based on initial EMR analysis of matched patients at the Wake Forest Baptist Health study site. There was no statistically significant difference in the average duration of time in the post-anesthesia care unit (PACU), with 2.4 hours observed for both Olinvyk-treated and matched patients (P=0.8174). Delirium. Twenty (4.4%) matched patients experienced ICD-coded delirium or altered consciousness, compared to one patient (1.0%) with Olinvyk, though this difference was not statistically significant (P=0.27.)

Patients receiving any IV opioid who experienced delirium or altered consciousness in this study had an average hospital length of stay 10.5 days longer than patients who did not experience this event. ICD-coding was used for this comparative analysis as 3D-CAM is not generally used in the general patient population.

Initial EMR Data Set. ARTEMIS is an electronic medical records (EMR) data analysis, with records available from the Wake Forest Baptist Health study site (n=96 Olinvyk-treated patients; n=457 matched patients on other IV opioids). While an EMR analysis does not provide definitive data of group differences as seen in a prospectively randomized study, we believe EMR data bring a unique perspective to an understanding of how drugs may perform in the real world.

VOLITION and ARTEMIS Study Details: VOLITION is a real-world, open-label, multi-site, post-approval clinical outcomes study in 203 adult patients undergoing major non-cardiac surgery. IV Olinvyk was dosed as the first-line analgesic during post-operative care, with a 1.5mg loading dose of Olinvyk at surgical closure, and 0.35mg to 0.5mg of Olinvyk, as needed, administered with a PCA device, with a 6-minute lockout period. Additional boluses (?1 mg) of Olinvyk were available if needed as soon as 15 minutes after the initial 1.5 mg loading dose.

The average age of patients in VOLITION was 57.1 years (range 19 to 89), with approximately equal representation of men and women. Approximately 85% of patients underwent an abdominal surgical intervention, such as partial or total colectomy, enterotomy or other open abdominal procedures. A majority of patients had significant morbidity at the time of surgery as reflected by an ASA status, and their respiratory risk was intermediate to high risk, graded using the PRODIGY risk score. The average duration of the surgery was 4.7 hours (range of 1.2 to 12.6 hours).

ARTEMIS is an EMR-based analysis that compared the health outcomes of VOLITION study patients with a matched population of patients, who underwent similar surgical procedures but were treated with other IV opioids, at the same institutions and during the same general time period as VOLITION. Matching was conducted with a greedy matching algorithm, using a propensity scoring method with eight different demographic and clinical characteristics including age, sex, type and duration of surgery, measures of overall surgical and medical morbidity, and type of hospital insurance.