Complete Response Letter for tramadol i.v. for the management of moderate to moderately severe pain.- Avenue Therapeutics

Avenue Therapeutics, Inc. , a company focused on the development of intravenous (“IV”) tramadol for the U.S. market, announced it has received a Complete Response Letter (“CRL”) from the FDA regarding the Company’s New Drug Application (“NDA”) for IV tramadol. The CRL stated that although the pivotal Phase III clinical trials demonstrated statistically significant outcomes for all of the primary and many secondary endpoints, the FDA has determined that it cannot approve the application in its present form. The CRL stated that IV tramadol, intended to treat patients in acute pain who require an opioid, is not safe for the intended patient population. Specifically, if a patient requires an analgesic between the first dose of IV tramadol and the onset of analgesia, a rescue analgesic would be needed. The likely choice would be another opioid, which would result in opioid “stacking” and increase the likelihood of opioid-related adverse effects. Other than this potential safety concern, the FDA did not identify a safety signal in Avenue’s clinical development program. In addition, the CRL stated that the FDA requires an adequate terminal sterilization validation prior to NDA approval, which is planned for later this quarter.