Hydrocodone controlled release(DURECT Corp)

iStock, hapabapa BMO Capital Markets analyst Evan Seigerman in a note to investors said the late-stage data for Vertex’s experimental non-opioid pain medication “reaffirms our confidence in the strength of suzetrigine’s profile.” However, William Blair analysts view these data as “an incremental positive” as the company faces challenges in targeting the acute pain market. Vertex Pharmaceuticals ’ investigational non-opioid pain therapy suzetrigine has a cleaner safety profile than standard pain relief medicines and even placebo, according to full Phase III data presented over the weekend at the 2024 annual meeting of the American Society of Anesthesiologists in Philadelphia. In study participants who were undergoing abdominoplasty—more commonly known as a tummy tuck—adverse events of any severity arose in 50% of patients given suzetrigine. By comparison, toxicities were detected in 60.7% of patients managed with hydrocodone bitartrate/acetaminophen (HB/APAP) and in 56.3% of placebo comparators. Suzetrigine continued to have a better safety pro HB/APAP and placebo even after disaggregating according to severity. Severe toxicities developed in 1.8% of abdominoplasty patients in the suzetrigine arm, versus 2% and 2.7% in HB/APAP and placebo counterparts, respectively. One patient in the placebo arm died. Similar safety findings were observed in patients who underwent bunionectomy, which is a surgical procedure to correct a bone deformity in the toes. Aside from the positive safety data, Vertex also reported an efficacy update for suzetrigine at ASA 2024. In abdominoplasty patients, suzetrigine monotherapy led to a 48.4-point improvement in pain scores, as measured by SPID48, a tool that measures time-weighted pain intensity from 0 to 48 hours after surgery. This effect was statistically significant, with a p-value less than 0.0001, according to Vertex’s presentation. While suzetrigine’s effect seems to be weaker in bunionectomy patients, it still remained significantly better than placebo. Mean SPID48 scores were 29.3 points higher after suzetrigine treatment versus placebo. Compared with the HB/APAP combo, however, suzetrigine monotherapy did not lead to significantly better pain relief. Mean SPID48 scores improved by only 6.6 points in abdominoplasty patients versus HB/APAP, an effect that fell short of significance. Meanwhile, in bunionectomy patients, mean SPID48 scores appear to have worsened by 20.2 points in the suzetrigine arm, which was statistically significant. Suzetrigine is an orally available pain signal inhibitor that works by targeting and binding to the NaV1.8 voltage-gated sodium channel. Typically found on pain-sensing neurons, these channels help transmit pain signals from the peripheral nervous system back to the spine and brain. NaV1.8 channels are validated pain targets. In July 2024, the FDA accepted Vertex’s New Drug Application for suzetrigine for moderate to severe acute pain, with a target action date on Jan. 30, 2025 . If approved, suzetrigine could provide patients with an effective non-opioid option for pain relief. BMO Capital Markets analyst Evan Seigerman in a note to investors said the detailed late-stage data for Vertex’s non-opioid pain medication “reaffirms our confidence in the strength of suzetrigine’s pro acute pain.” However, William Blair analysts in a note to investors said they view Vertex’s presentation at ASA 2024 as “an incremental positive” for suzetrigine with some challenges as the company targets the acute pain market. “In the post-surgical outpatient setting, we continue to believe suzetrigine has a strong argument for inclusion in the market but note that pricing remains a point of investor contention along with how this impacts reimbursement, formulary placement, and prior authorization requirements, the latter of which Vertex is keen to avoid,” the analysts wrote. Truist Securities analyst Joon Lee in a note said his firm is “not entirely sold yet on the commercial case for suzetrigine in acute pain,” adding that “if there is indeed will to use non-opioid analgesic, we think there are numerous options that are readily available that will be significantly cheaper than suzetrigine.”

SMART™ opioid prodrugs leverage Elysium's O2P (Oral Overdose Protected) technology to effectively mitigate non-oral and oral abuse while safely delivering FDA-cleared opioid agonists, which continue to play a vital role in the treatment of acute pain Phase 1 results demonstrated effective acute pain relief while simultaneously mitigating the major risks of existing opioids by protecting against abuse, diversion, and fatal overdose LYONS, Colo., Sept. 3, 2024 /PRNewswire/ -- Elysium Therapeutics, an emerging biopharmaceutical company establishing new standards for safety in the opioid industry by developing SMART™ (Safer Medicines Alleviate Risks and Trauma) products, first- and best-in-class medicines to address the limitations and dangers associated with opioids and overdose rescue agents, today announced its Phase 1, human-proof-of-concept study investigating the company's proprietary Oral Overdose Protected (O2P™) hydrocodone prodrug for the treatment of moderate-to-severe acute pain will be presented at PAINWeek 2024 being held September 3-6 in Las Vegas. The poster titled, "SMART™ Opioids with Unprecedented Protection Against Abuse and Oral Overdose – Human Proof-of-Concept", evaluates the safety, tolerability, and pharmacokinetics of oral O2P Hydrocodone relative to a hydrocodone bitartrate (HCBT) comparator following single oral doses in healthy adult subjects. The presentation of the successful Phase 1 study outlines a promising and novel approach, providing effective acute pain relief while simultaneously mitigating the major risks of existing opioids by protecting against abuse, diversion, and fatal overdose. The Phase 1 study achieved several key milestones, demonstrating a significant reduction in the number of prescribed doses that mitigates misuse, abuse, and diversion. Additionally, the authors were able to show that oral O2P Hydrocodone has the potential to limit the number of euphoric experiences that may serve to initiate and reinforce abusive behavior. "A key finding we look forward to presenting is the sustained plasma exposure of hydrocodone with O2P Hydrocodone, which is consistent with a once-daily dosing regimen," said Tom Jenkins, Ph.D., Co-Founder and Chief Scientific Officer of Elysium Therapeutics and inventor of trypsin-activated opioid prodrugs and concomitant use of trypsin inhibition to govern opioid exposure. "As a consequence, we anticipate being able to significantly reduce the number of prescribed tablets for O2P Hydrocodone compared to currently prescribed hydrocodone. Additionally, the O2P Hydrocodone technology is designed to attenuate hydrocodone exposures when supratherapeutic doses are ingested dramatically reducing the number of euphoric experiences available from an O2P Hydrocodone prescription." "Elysium is on a mission to establish a new standard of safety in the opioid industry, so we look forward to presenting our Phase 1 Proof-of-Concept findings for our O2P Hydrocodone technology, which we believe can significantly reduce the risk of fatal overdoses while providing the unmatched effective management of acute pain possible with opioid treatment," said Greg Sturmer, Co-Founder and CEO of Elysium Therapeutics. "For decades, as the opioid crisis has ravaged the nation, drug developers have largely failed to bring effective solutions for pain management to the clinic that offer a solution to the broader problems of abuse. We believe O2P Hydrocodone can be an important step in bringing solutions to this immense challenge." Poster Information: Title: SMART™ Opioids with Unprecedented Protection Against Abuse and Oral Overdose – Human Proof-of-Concept Authors: T. Jenkins, Ph.D., Lynn R. Webster, M.D., Leela Vrishabhendra, M.D., A. Greg Sturmer Time & Location: PAINWeek 2024, September 3-6 at The Cosmopolitan of Las Vegas About O2P™ Hydrocodone Elysium's lead product candidate – oral-overdose protected (O2P) hydrocodone – is a hydrocodone prodrug being developed for the treatment of moderate-to-severe acute pain. Elysium leverages its proprietary bifunctional prodrug technology, containing a trypsin-activated opioid delivery subunit that efficiently releases therapeutic levels of hydrocodone when exposed to the digestive enzyme trypsin in the lumen of the small intestine, and a trypsin inhibitor subunit that progressively inhibits trypsin, attenuating the release of hydrocodone when supratherapeutic doses are ingested. About the Phase 1 O2P-001 Study O2P-001 was a Phase 1, human proof-of-concept, randomized, open-label, two-part study designed to evaluate the safety and pharmacokinetics of O2P hydrocodone in healthy adult subjects. The key objectives of the study were to (i) evaluate the safety, tolerability, and pharmacokinetics of O2P hydrocodone relative to a hydrocodone comparator following single oral doses in healthy adult subjects with naltrexone blockade; and (ii) demonstrate reduced dose-proportional plasma exposures of hydrocodone (i.e., oral overdose protection) of O2P hydrocodone relative to an escalated comparator dose of hydrocodone. A total of 93 subjects were enrolled in the study. About Elysium Therapeutics Elysium is an emerging biopharmaceutical company that is establishing new standards of safety in the opioid industry by developing SMART™ (Safer Medicines Alleviate Risks and Trauma) products, first- and best-in-class medicines that address the limitations and dangers associated with opioids and overdose rescue agents to reduce suffering from opioid-use disorder, opioid overdose, and acute pain. Elysium's lead SMART opioid product candidate – oral-overdose protected (O2P™) hydrocodone – is being developed for the treatment of moderate-to-severe acute pain. Elysium is also developing its SMART rescue medicine, SOOPR™ (Synthetic Opioid Overdose Prevention and Reversal), a long-acting opioid antagonist specifically designed to address oral synthetic opioid, including fentanyl, overdose. Tens of thousands of unnecessary overdose deaths each year exemplifies the critical shortcomings of currently available rescue agents, including naloxone and nalmefene. For more information, please visit . SOURCE Elysium Therapeutics