Trevena Inc.

OLINVYK showed a statistically significant reduced impact on respiratory function compared to IV morphine, among elderly/overweight subjects

Data replicate observations previously seen in a comparative study of respiratory physiology in younger subjects with OLINVYK and IV morphine

CHESTERBROOK, Pa., April 20, 2022 (GLOBE NEWSWIRE) -- Trevena, Inc. (Nasdaq: TRVN), a biopharmaceutical company focused on the development and commercialization of novel medicines for patients with central nervous system (CNS) disorders, today announced results from its double blinded, crossover study evaluating OLINVYK (oliceridine) injection for the management of acute pain, in elderly/overweight. This study builds on the collaborative work with Dr. Albert Dahan and his research team at Leiden University Medical Center (LUMC).

We are very pleased with the results of our study, which replicate earlier results reported in younger subjects, said Dr. Albert Dahan, Professor of Anesthesiology at Leiden University Medical Center, These data suggest that OLINVYK, a new chemical entity, may offer a more favorable respiratory safety profile when compared to IV morphine.

Dr. Dahans team compared the analgesic and respiratory effects of two doses of OLINVYK (0.5mg and 2.0mg) and morphine (2.0mg and 8.0mg) administered intravenously in a population of elderly individuals (age range 56 to 87 years, mean age = 71.2) across a range of body weight (BMI range from 20 to 34 kg/m2, mean BMI= 26.3). Subjects were tested on 4 occasions and randomized by drug and dose. On each visit, the ventilatory response to inhaled carbon dioxide was measured to evaluate the potential effect of the drug on the brain respiratory centers. Elderly and overweight patients are known to be at higher risk of respiratory depression with the use of opioid medications. This study hypothesized that, at similar levels of analgesia, there would be a reduced impact on respiratory function with OLINVYK compared to IV morphine. The primary endpoint of the study was ventilatory rate at an extrapolated PCO2 of 55 mmHg (VE55).

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Key Findings

Both OLINVYK and IV morphine achieved comparable levels of pain relief. However, a statistically significantly reduced impact on respiratory function was observed in patients treated with OLINVYK compared to IV morphine, as measured by the mean respiratory ventilation profiles over time (P < 0.0001).

In contrast to the lower dose of IV morphine, very little impact on respiratory function was observed with the lower dose of OLINVYK.

At the higher dose of both drugs studied, less respiratory depression over the 6 h measurement period was observed with OLINVYK. The peak level was lower for OLINVYK compared to morphine, though this difference was not statistically significant (P > 0.05). In addition, in contrast to morphine, respiratory function at the higher dose of OLINVYK rapidly returned toward baseline from 3 hours onward (all time points P < 0.05 in pairwise comparison).

The data replicate the results from a previously reported study in younger subjects.

Comparing the sensitivity of the impact on respiratory function from the earlier study and the results from the current study suggests that there is a nearly identical impact on respiratory function with OLINVYK in the younger and elderly age groups, while IV morphine data suggests an increase in impact in the elderly compared to the younger subjects.

We believe these data from Dr. Dahans study team are important. They replicate the results from an earlier study reported by Trevena in younger subjects using a similar methodology, and they extend our knowledge to patients who are at higher risk for the development of respiratory depression with the use of opioids, namely elderly and overweight patients, said Mark A. Demitrack, M.D., Senior Vice President and Chief Medical Officer of Trevena. As with all opioids, serious, life-threatening, or fatal respiratory depression may occur in patients treated with OLINVYK. We look forward to seeing further analysis of this data by Dr. Dahans team and working with him to see these results reported to the wider scientific community and submitted for publication in the near future.

About OLINVYK (oliceridine) injection

OLINVYK is a new chemical entity approved by the FDA in August 2020. OLINVYK contains oliceridine, an opioid, which is a Schedule II controlled substance with a high potential for abuse similar to other opioids. It is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. OLINVYK is available in 1 mg/1 mL and 2 mg/2 mL single-dose vials, and a 30 mg/30 mL single-patient-use vial for patient-controlled analgesia (PCA). Approved PCA doses are 0.35 mg and 0.5 mg and doses greater than 3 mg should not be administered. The cumulative daily dose should not exceed 27 mg. Please see Important Safety Information, including the BOXED WARNING, and full prescribing information at http://www.OLINVYK.com.

IMPORTANT SAFETY INFORMATIONWARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CENTRAL NERVOUS SYSTEM (CNS) DEPRESSANTS

ADDICTION, ABUSE, AND MISUSE OLINVYK exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patients risk before prescribing OLINVYK, and monitor all patients regularly for the development of behaviors or conditions.

LIFE-THREATENING RESPIRATORY DEPRESSION Serious, life-threatening, or fatal respiratory depression may occur with use of OLINVYK. Monitor for respiratory depression, especially during initiation of OLINVYK or following a dose increase.

NEONATAL OPIOID WITHDRAWAL SYNDROME Prolonged use of OLINVYK during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

RISK FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation.

INDICATIONS AND USAGEOLINVYK is an opioid agonist indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate.Limitations of UseBecause of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve OLINVYK for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]:

Have not been tolerated, or are not expected to be tolerated

Have not provided adequate analgesia, or are not expected to provide adequate analgesia.

The cumulative total daily dose should not exceed 27 mg, as total daily doses greater than 27 mg may increase the risk for QTc interval prolongation.CONTRAINDICATIONSOLINVYK is contraindicated in patients with:

Significant respiratory depression

Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment

Known or suspected gastrointestinal obstruction, including paralytic ileus

Known hypersensitivity to oliceridine (e.g., anaphylaxis)

WARNINGS AND PRECAUTIONS

OLINVYK contains oliceridine, a Schedule II controlled substance, that exposes users to the risks of addiction, abuse, and misuse. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed OLINVYK. Assess risk, counsel, and monitor all patients receiving opioids.

Serious, life-threatening respiratory depression has been reported with the use of opioids, even when used as recommended, especially in patients with chronic pulmonary disease, or in elderly, cachectic and debilitated patients. The risk is greatest during initiation of OLINVYK therapy, following a dose increase, or when used with other drugs that depress respiration. Proper dosing of OLINVYK is essential, especially when converting patients from another opioid product to avoid overdose. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patients clinical status.

Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia with risk increasing in a dose-dependent fashion. In patients who present with CSA, consider decreasing the dose of opioid using best practices for opioid taper.

Prolonged use of opioids during pregnancy can result in withdrawal in the neonate that may be life-threatening. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using OLINVYK for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

Profound sedation, respiratory depression, coma, and death may result from the concomitant use of OLINVYK with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, or alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate, prescribe the lowest effective dose, and minimize the duration.

OLINVYK was shown to have mild QTc interval prolongation in thorough QT studies where patients were dosed up to 27 mg. Total cumulative daily doses exceeding 27 mg per day were not studied and may increase the risk for QTc interval prolongation. Therefore, the cumulative total daily dose of OLINVYK should not exceed 27 mg.

Increased plasma concentrations of OLINVYK may occur in patients with decreased Cytochrome P450 (CYP) 2D6 function or normal metabolizers taking moderate or strong CYP2D6 inhibitors; also in patients taking a moderate or strong CYP3A4 inhibitor, in patients with decreased CYP2D6 function who are also receiving a moderate or strong CYP3A4 inhibitor, or with discontinuation of a CYP3A4 inducer. These patients may require less frequent dosing and should be closely monitored for respiratory depression and sedation at frequent intervals. Concomitant use of OLINVYK with CYP3A4 inducers or discontinuation of a moderate or strong CYP3A4 inhibitor can lower the expected concentration, which may decrease efficacy, and may require supplemental doses.

Cases of adrenal insufficiency have been reported with opioid use (usually greater than one month). Presentation and symptoms may be nonspecific and include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If confirmed, treat with physiologic replacement doses of corticosteroids and wean patient from the opioid.

OLINVYK may cause severe hypotension, including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics). Monitor these patients for signs of hypotension. In patients with circulatory shock, avoid the use of OLINVYK as it may cause vasodilation that can further reduce cardiac output and blood pressure.

Avoid the use of OLINVYK in patients with impaired consciousness or coma. OLINVYK should be used with caution in patients who may be susceptible to the intracranial effects of CO2 retention, such as those with evidence of increased intracranial pressure or brain tumors, as a reduction in respiratory drive and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy.

As with all opioids, OLINVYK may cause spasm of the sphincter of Oddi, and may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.

OLINVYK may increase the frequency of seizures in patients with seizure disorders and may increase the risk of seizures in vulnerable patients. Monitor patients with a history of seizure disorders for worsened seizure control.

Do not abruptly discontinue OLINVYK in a patient physically dependent on opioids. Gradually taper the dosage to avoid a withdrawal syndrome and return of pain. Avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving OLINVYK, as they may reduce the analgesic effect and/or precipitate withdrawal symptoms.

OLINVYK may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.

Although self-administration of opioids by patient-controlled analgesia (PCA) may allow each patient to individually titrate to an acceptable level of analgesia, PCA administration has resulted in adverse outcomes and episodes of respiratory depression. Health care providers and family members monitoring patients receiving PCA analgesia should be instructed in the need for appropriate monitoring for excessive sedation, respiratory depression, or other adverse effects of opioid medications.

ADVERSE REACTIONSAdverse reactions are described in greater detail in the Prescribing Information.The most common (incidence 10%) adverse reactions in Phase 3 controlled clinical trials were nausea, vomiting, dizziness, headache, constipation, pruritus, and hypoxia.MEDICAL INFORMATIONFor medical inquiries or to report an adverse event, other safety-related information or product complaints for a company product, please contact the Trevena Medical Information Contact Center at 1-844-465-4686 or email MedInfo@Trevena.com.You are encouraged to report suspected adverse events of prescription drugs to the FDA. Visit http://www.fda.gov/medwatch or call 1-800-FDA-1088.Please see Full Prescribing Information, including Boxed Warning.

About Trevena

Trevena, Inc. is a biopharmaceutical company focused on the development and commercialization of innovative medicines for patients with CNS disorders. The Company has one approved product in the United States, OLINVYK (oliceridine) injection, indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. The Companys novel pipeline is based on Nobel Prize winning research and includes four differentiated investigational drug candidates: TRV045 for diabetic neuropathic pain and epilepsy, TRV027 for acute respiratory distress syndrome and abnormal blood clotting in COVID-19 patients, TRV250 for the acute treatment of migraine and TRV734 for maintenance treatment of opioid use disorder.

For more information, please visit http://www.Trevena.com

Forward-Looking Statements

Any statements in this press release about future expectations, plans and prospects for the Company, including statements about the Companys strategy, future operations, clinical development and trials of its therapeutic candidates, plans for potential future product candidates and other statements containing the words anticipate, believe, estimate, expect, intend, may, plan, predict, project, suggest, target, potential, will, would, could, should, continue, and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the status, timing, costs, results and interpretation of the Companys clinical trials or any future trials of any of the Companys investigational drug candidates; the uncertainties inherent in conducting clinical trials; expectations for regulatory interactions, submissions and approvals, including the Companys assessment of discussions with FDA; available funding; uncertainties related to the Companys intellectual property; uncertainties related to the ongoing COVID-19 pandemic, other matters that could affect the availability or commercial potential of the Companys therapeutic candidates and approved product; and other factors discussed in the Risk Factors set forth in the Companys Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in other filings the Company makes with the SEC from time to time. In addition, the forward-looking statements included in this press release represent the Companys views only as of the date hereof. The Company anticipates that subsequent events and developments may cause the Companys views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, except as may be required by law.

For more information, please contact:

Investor Contact:

Dan FerryManaging DirectorLifeSci Advisors, LLCdaniel@lifesciadvisors.com(617) 430-7576

PR & Media Contact:

Sasha BennettAssociate Vice PresidentClyde GroupSasha.Bennett@clydegroup.com(239) 248-3409

Company Contact:

Bob YoderSVP and Chief Business OfficerTrevena, Inc.(610) 354-8840

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Trevena Announces Results from Respiratory Physiology Study of Head-to-Head Comparison of OLINVYK and IV Morphine in Elderly/Overweight Subjects -...