Morphine-6-glucuronide

Al Drago/CQ Roll Call The FDA committee voted 8 yes and 14 no. The decision now goes back to the OND to decide the FDDR on Avenue Therapeutics’ IV Tramadol. Al Drago/CQ Roll Call On February 15, 2022, the U.S. Food and Drug Administration held a joint meeting of the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee on Avenue Therapeutics ’ IV tramadol. In the final part of the meeting, which was public, the Advisory Committee made a yes-no vote on the following question: “Has the Applicant submitted adequate information to support the position that the benefits of their product outweigh the risks of the management of acute pain severe enough to require an opioid analgesic in an inpatient setting?” The committee voted 8 yes and 14 no. The decision now goes back to the FDA’s Office of New Drugs (OND) to decide the Formal Dispute Resolution Request (FDDR). It will provide a response within 30 calendar days. On June 14, 2021, the FDA issued a second Complete Response Letter (CRL) to Avenue over its New Drug Application (NDA) for IV tramadol. The letter indicated that the “delayed and unpredictable onset of analgesia with IV tramadol does not support its benefit as a monotherapy to treat patients in acute pain.” It also indicated the safety and efficacy data were insufficient. The company stated that it didn’t agree with the agency and planned to continue to pursue regulatory approval. The first CRL was issued on October 12, 2020. Then on October 25, 2021, Avenue reported it had received a written interim response from the FDA’s OND to the company’s formal dispute resolution request. The response indicated the OND needed additional feedback from an advisory committee to help plan on the FDDR. The first CRL in October 2020 indicated that even though the pivotal Phase III trials demonstrated statistically significant outcomes for the primary endpoint and many secondary endpoints, the agency couldn’t approve it in its present form. The agency did not believe that the drug was safe for the intended patient population, which is patients in acute pain who require an opioid. They specifically noted that “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.” At the time, Dr. Lucy Lu, president and chief executive officer of Avenue, stated, “We believe that our extensive clinical database strongly supports the value of treatment with IV tramadol as an effective alternative to intravenous Schedule II conventional opioids. We firmly stand behind the safety data in our NDA and the ultimate approvability of IV tramadol.” According to a brief by Public Citizen, IV tramadol requires a median time of 106 minutes after surgery for effective pain relief. However, IV morphine only requires 42 minutes. Dr. Sidney Wolfe, senior advisor to Public Citizen’s Health Research Group, testified at the advisory committee meeting, saying, in part, “Since ‘approximately 50% of patients administered tramadol IV 50 mg did not report meaningful pain relief in 6 hours,’ I agree with FDA’s concern that patients will need additional opioids, thereby severely reducing the efficacy of the IV tramadol and increasing risk such as respiratory depression.” On December 15, 2021, Avenue announced the closing of its public offering of 1,910,100 shares of common stock at a public offering price of $1.07, which brought in about $2 million. It trades on The Nasdaq Capital Market under the ATXI ticker symbol. The Nasdaq had halted trading yesterday due to the advisory committee hearing. Based in New York City, Avenue Therapeutics was founded by Fortress Biotech . The company’s sole focus is on developing an IV formulation of tramadol as an alternative to conventional opioids.

Al Drago/CQ Roll Call Mid-November is a relatively quiet period for the U.S. Food and Drug Administration in terms of its scheduled PDUFA dates. Read on for more. Al Drago/CQ Roll Call Mid-November is a relatively quiet period for the U.S. Food and Drug Administration (FDA) in terms of its scheduled PDUFA dates. Read on for more. Liquidia’s Treprostinil for Pulmonary Arterial Hypertension Liquidia Corporation has a target action date of November 7, 2021, for its New Drug Application (NDA) resubmission. The NDA is for LIQ861 (Treprostinil) inhalation powder to treat pulmonary arterial hypertension (PAH). The FDA had confirmed in June 2021 that the resubmission was a complete, class 2 response for its previous action letter issued on November 24, 2020. The product is an inhaled dry powder formulation of Treprostinil designed with Liquidia’s PRINT technology. The design is to improve deep-lung delivery with a palm-sized dry powder inhaler. At the company’s third-quarter financial report on November 3, Liquidia reported that in the quarter unit sales of Treprostinil Injection increased across both intravenous and subcutaneous routes of administration. They more than doubled the number of patients treated compared to patients before the launch of the subcutaneous administration in late May 2021. In addition, as part of the FDA review of the inhaled formulation, the agency conducted two prior-approval inspections, one at Liquidia’s Morrisville, NC facility and the other one at a plant of a third-party provider that handled encapsulation and packing services. They were completed in August 2021 and October 2021, respectively. PAH is high blood pressure in the arteries of the lungs. It is both chronic and progressive. Over time it will worsen and can limit physical activities. Adamis’ ZIMHI for Opioid Overdose Adamis Pharmaceuticals Corporation had a target action date of November 12 for its resubmitted NDA for Zimhi. The drug is a higher naloxone injection for the treatment of opioid overdose. In June, the FDA told the company it had completed its review of the filing and decided it was complete enough to allow a substantive review and set the date in November. The drug is an opioid antagonist to treat narcotic overdoses. Common opioids include morphine, heroin, tramadol, oxycodone, hydrocodone and fentanyl. On October 18, the agency approved the drug for use in the treatment of opioid overdose. P. Breckinridge Jones, Sr., chief executive officer of US WorldMeds, who is acting as Adamis’ commercial partner, said, “We are pleased with the approval and now look forward to commercially marketing Zimhi in the United States. US WorldMeds has a proven track-record of successfully commercializing pharmaceutical products and have a First-in-Class and only FDA-approved product, Lucemyra (lofexidine), for the treatment of withdrawal symptoms associated with abrupt opioid discontinuation. We are confident we can leverage our existing commercial infrastructure and presence in the opioid dependence market to speed the uptake of Zimhi and combat the growing opioid crisis. We are preparing for the full commercial launch of Zimhi which is planned for the first quarter of 2022.” BioMarin’s Vosoritide for Achondroplasia BioMarin Pharmaceuticals has a target action date of November 20 for its NDA for vosoritide for achondroplasia, a form of short-limbed dwarfism. The agency originally had an earlier target action date, but the company provided the FDA with the two-year data from the Phase III extension study of the drug to supplement the NDA. As expected, the agency said it was a major amendment and extended the PDUFA date by three months. In addition, in the first quarter of 2021, the FDA ran a pre-approval inspection of BioMarin’s Novato facility for manufacturing of vasoritide drug substance. On August 27, the European Commission (EC) granted marketing authorization for the drug with the brand name Voxzogo for once daily injection to treat achondroplasia in children from the age of two until growth plates are closed. It was the first drug to be approved for this indication in Europe. The drug is a modified C-type natriuretic peptide (CNP), which downregulates fibroblast growth factor receptor 3 (FGFR3) signaling and promotes endochondral bone formation.