A Comparison of the Analgesic Effects of Rectus Sheath and Transversus Thoracis Plane Blocks (ABC Blocks) Versus Saline Injection for Median Sternotomy: a Prospective, Randomized Controlled Trial.

This randomized blinded trial aims to evaluate the effect of parasternal intercostal and rectus sheath blocks ("anterior blocks for cardiac surgery" or ABC blocks) on postoperative recovery in patients undergoing median sternotomy for cardiac surgery. Subjects will be randomized to receive either local anesthetic (liposomal bupivacaine plus bupivacaine 0.25%) or saline sham block.

Start Date01 Nov 2024

Sponsor / Collaborator

Duke University

NCT06456255 / Not yet recruitingPhase 2/3

Bupivacaine With Epinephrine vs Sham Injections During Endoscopic Sinus Surgery: a Double Blind, Randomized Controlled Trial

Endoscopic sinus surgery (ESS) is a common otolaryngologic procedure that aims to remove the partitions that separate the sinus cavities, remove inflamed tissue, and optimize the sinuses for topical medication use. In this procedure, the surgeon will inject a combination of drugs, local anesthetics, and vasoconstrictors, to reduce bleeding and improve visualization. However, previous studies have shown similar results when injected with only saline. In this study, investigators want to determine if the injection of local anesthesic+vasoconstrictor compared to no injection at all makes any difference in improving the surgeon's visualization during an ESS.

Start Date01 Jul 2024

Sponsor / Collaborator

St. Paul's Hospital (Grey Nuns) of Saskatoon

NCT06450028 / Not yet recruitingPhase 4IIT

Lidocaine Versus Bupivacaine in Orthognathic Surgery: A Randomized Controlled Trial

In this research study, we want to learn more about the impact of two different local anesthetics (bupivacaine and lidocaine) on patient experience following orthognathic (jaw) surgery. Both anesthetics are within the standard of care for dental and orthognathic procedures, but can vary in how quickly they take action and how long they last. This study will provide us with a greater understanding of how anesthetic choice affect patient outcomes, and how we can strive to make these outcomes as favorable as possible.

Start Date10 Jun 2024

Sponsor / Collaborator

The Children's Hospital Corp.

100 Clinical Results associated with Bupivacaine Hydrochloride

100 Translational Medicine associated with Bupivacaine Hydrochloride

100 Patents (Medical) associated with Bupivacaine Hydrochloride

851

Literatures (Medical) associated with Bupivacaine Hydrochloride

01 Dec 2024·Techniques in coloproctology

Liposomal bupivacaine versus conventional anesthetic or placebo for hemorrhoidectomy: a systematic review and meta-analysis

Review

Author: Schleicher, M ; Solis-Pazmino, P ; Cohen, J ; La, K ; Nasseri, Y ; Figueroa, L ; Termeie, O ; Oka, K ; Barnajian, M

Abstract:

Background:

Liposome bupivacaine (LB) is a long-acting anesthetic to enhance postoperative analgesia. Studies evaluating the efficacy of the LB against an active comparator (bupivacaine or placebo) on acute postoperative pain control in hemorrhoidectomy procedures are few and heterogeneous. Therefore, we performed a systematic review and meta-analysis comparing LB’s analgesic efficacy and side effects to conventional/placebo anesthetic in hemorrhoidectomy patients.

Methods:

We performed a systematic review and meta-analysis of randomised controlled trials investigating the use of LB after haemorrhoidectomy. We searched the literature published from the time of inception of the datasets to August 19, 2022. The electronic databases included English publications in Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, and Scopus.

Results:

A total of 338 patients who underwent a hemorrhoidectomy procedure enrolled in three randomized clinical trials were included. The overall mean age was 45.84 years (SD ± 11.43), and there was a male predominance (53.55% male). In total 194 patients (52.2%) received LB and 144 (47.8%) received either bupivacaine or placebo. Pain scores at 72 h in the LB (199, 266, and 300 mg) were significantly lower than in the bupivacaine HCl group (p = 0.002). Compared to the bupivacaine/placebo group, the time to first use of opioids in the LB group was significantly longer at LB 199 mg (11 h vs. 9 h), LB 266 mg (19 h vs. 9 h), and LB 300 mg (19 h vs. 8 h) (p < 0.05). Moreover, compared to the bupivacaine/epinephrine group, it was significantly lower in the LB 266 mg group (3.7 vs. 10.2 mg) and at LB 300 mg (13 vs. 33 mg) (p < 0.05). Finally, regarding adverse effects, the conventional anesthetic/placebo group reported more pain in bowel movement than LB groups (OR 2.60, 95% CI 1.31–5.16).

Conclusions:

Comparing LB to conventional anesthetic/placebo anesthetic for hemorrhoidectomy, we found a statistically significant reduction in pain through 72 h, decreased opioid requirements, and delayed time to first opioid use. Moreover, the conventional anesthetic/placebo group reported more pain in bowel movement than LB groups.

01 Jan 2024·The Journal of urology

Effectiveness of Liposomal Bupivacaine With Bupivacaine Hydrochloride vs Bupivacaine Hydrochloride Alone as a Local Anesthetic for Children Undergoing Ambulatory Urologic Surgery: The Baby ORIOLES Randomized Clinical Trial

Article

Author: Harris, Kelly ; Wang, Ming-Hsien ; Crigger, Chad ; Jing, Yuezhou ; Galansky, Logan ; Gearhart, John P ; Wu, Charlotte ; Di Carlo, Heather N ; Gabrielson, Andrew T ; Patel, Hiten D ; Sholklapper, Tamir ; Haney, Nora

PURPOSE:

We sought to determine if the addition of liposomal bupivacaine to bupivacaine hydrochloride improves opioid-free rate and postoperative pain scores among children undergoing ambulatory urologic surgery.

MATERIALS AND METHODS:

A prospective, phase 3, single-blinded, single-center randomized trial with superiority design was conducted in children 6 to 18 years undergoing ambulatory urologic procedures between October 2021 and April 2023. Patients were randomized 1:1 to receive dorsal penile nerve block (penile procedures) or incisional infiltration with spermatic cord block (inguinal/scrotal procedures) with weight-based liposomal bupivacaine plus bupivacaine hydrochloride or bupivacaine hydrochloride alone. The primary outcome was opioid-free rate at 48 hours. Secondary outcomes included parents' postoperative pain measure scores, numerical pain scale scores, and weight-based opioid utilization at 48 hours and 10 to 14 days.

RESULTS:

We randomized 104 participants, with > 98% (102/104) with complete follow-up data at 48 hours and 10 to 14 days. At interim analysis, there was no significant difference in opioid-free rate at 48 hours between arms (60% in the intervention vs 62% in the control group; estimated difference in proportion -1.9% [95% CI, -20%-16%]; P = .8). We observed no increased odds of patients being opioid-free at 48 hours with the intervention compared to the control group (OR 0.96 [95% CI 0.41-2.3]; P = .9). The trial met the predetermined futility threshold for early stopping. There was no difference in parents' postoperative pain measure scores, numerical pain scale scores, or opioid utilization at 48 hours or 10 to 14 days. No difference in adverse events was observed.

CONCLUSIONS:

The addition of liposomal bupivacaine to bupivacaine hydrochloride did not significantly improve opioid-sparing effect or postoperative pain compared with bupivacaine hydrochloride alone among children ≥ 6 years undergoing ambulatory urologic surgery.

01 Dec 2023·Regional anesthesia and pain medicine

A randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a bupivacaine hydrochloride implant in patients undergoing abdominoplasty.

Article

Author: Solanki, Daneshvari ; Singla, Neil ; Skuban, Nina ; Folkerth, Steve ; Niebler, Gwendolyn ; Beaton, Alina C ; Leiman, David ; Salazar, Hernan ; Vaughn, Ben ; Minkowitz, Harold S

INTRODUCTION:

Surgical site infiltration with bupivacaine hydrochloride (HCl) is a standard element of postoperative analgesia for soft tissue surgeries, but results in short-lived analgesia. A novel bupivacaine implant, XARACOLL (bupivacaine HCl), is Food and Drug Administration approved for treatment of acute postsurgical pain following adult inguinal herniorrhaphy. This study examined the efficacy and safety of the bupivacaine implant (300 mg) compared with placebo for postsurgical pain after abdominoplasty.

METHODS:

In this double-blind, placebo-controlled study, patients undergoing abdominoplasty were randomized to three 100 mg bupivacaine implants or three placebo collagen implants, in a 1:1 ratio, implanted intraoperatively. No other analgesics were administered into the surgical site. Patients were allowed opioids and acetaminophen for postoperative pain. Patients were followed for up to 30 days after treatment.

PRIMARY OUTCOME:

the analgesic effect of the bupivacaine implants through 24 hours postsurgery, measured by the sum of time-weighted pain intensity (SPI24). Prespecified key secondary outcomes included SPI48 and SPI72, percentage of opioid-free patients through 24, 48, and 72 hours, and adverse events, which were tested sequentially to control for multiplicity (ie, if the first variable failed to reach significance, no subsequent variables were declared statistically significant).

RESULTS:

The bupivacaine implant patients (n=181) reported statistically significant lower SPI24 (mean (SD) SPI24=102 (43), 95% CI 95 to 109) compared with placebo patients (n=184; SPI24=117 (45), 95% CI 111 to 123, p=0.002). SPI48 was 190 (88, 95% CI 177 to 204) for INL-001 and 206 (96, 95% CI 192 to 219) for placebo, and not significantly different between groups. The subsequent secondary variables were therefore declared not statistically significant. SPI72 was 265 (131, 95% CI 244 to 285) for INL-001 and 281 (146, 95% CI 261 to 301) for placebo. The opioid-free percentage of patients at 24, 48, and 72 hours was 19%, 17%, and 17% for INL-001 and 6.5% for placebo patients (at all timepoints). The only adverse event occurring in ≥5% of patients and for which proportion INL-001 >placebo was back pain (7.7% vs 7.6%).

CONCLUSION:

The study design was limited by not containing an active comparator. Compared with placebo, INL-001 provides postoperative analgesia that is temporally aligned with the period of maximal postsurgical pain in abdominoplasty and offers a favorable safety profile.

TRIAL REGISTRATION NUMBER:

NCT04785625.

News (Medical) associated with Bupivacaine Hydrochloride

21 Jun 2024

·www.biospace.com

Acasti Announces Year-End 2024 Financial Results, Provides Business Update

Patient Enrollment in Pivotal STRIVE-ON Phase 3 Safety Trial for GTX-104 On-Track for Potential NDA Submission in 1H Calendar 2025 Projected Cash Runway into Second Calendar Quarter 2026 PRINCETON, N.J., June 21, 2024 (GLOBE NEWSWIRE) -- Acasti Pharma Inc. (Nasdaq: ACST) (Acasti or the Company), a late-stage, biopharma company advancing GTX-104, its novel injectable formulation of nimodipine that addresses high unmet medical needs for a rare disease, aneurysmal subarachnoid hemorrhage (aSAH), today announced financial results and business highlights for the year ended March 31, 2024. "During the past year we continued to execute our focused strategy around our biggest value driver program GTX-104 and its pivotal Phase 3 STRIVE-ON safety trial (the STRIVE-ON trial–NCT05995405),” said Prashant Kohli, CEO of Acasti. “Since initiating STRIVE-ON and dosing the first patient last October, enrollment has proceeded steadily, and we believe the trial is on track for a potential NDA submission to the FDA in the first half of calendar 2025. With our balance sheet enhanced by the $7.5 million private placement secured in September 2023, and disciplined execution of the strategic realignment plan we announced in May 2023, our cash runway is expected to extend into the second calendar quarter of 2026, well beyond our planned submission of the GTX-104 NDA.” 2024 Corporate Highlights Overview of STRIVE-ON trial, a prospective, open-label, randomized (1:1 ratio), parallel group trial of GTX-104 compared with oral nimodipine, in patients hospitalized for aSAH, presented as a poster at the 2024 International Stroke Conference Enrollment of STRIVE-ON trial on track for potential NDA submission to FDA anticipated in the first half of calendar 2025 Conducted a meeting of STRIVE-ON trial investigators in April 2024; the in-person/virtual meeting provided an excellent opportunity to energize the principal investigators from all sites, engage in an interactive discussion about the trial inclusion/exclusion criteria, and to review key procedures to ensure quality data collection In October 2023 hosted a Key Opinion Leader Event GTX-104: A Potential New Treatment Standard for Rare and Life-Threatening aneurysmal Subarachnoid Hemorrhage (aSAH) Completed $7.5 million private placement equity financing led by ADAR1 Partners, LP in September 2023 Presented a pharmacokinetic comparison of GTX-104 with oral nimodipine at the 2023 Neurocritical Care Society annual meeting in August 2023. Fiscal Year 2024 Financial Results The Company reported a net loss of $12.9 million, or $1.35 loss per share, for the year ended March 31, 2024, a decrease of $29.5 million from the net loss of $42.4 million or $5.71 per share for the year ended March 31, 2023. The decrease in net loss was primarily due to asset impairments, net of income tax benefit, totaling $25.3 million during the year ended March 31, 2023 that did not recur during the year ended March 31, 2024, the impact of the Company’s strategic realignment in May 2023 to align the organizational and management cost structure to prioritize resources to GTX-104, and the change in fair value of the Company’s derivative warrant liabilities that was primary attributable to an increase in stock price. Research and development expenses for the year ended March 31, 2024 were $4.7 million, compared to $10.0 million for the year March 31, 2023. The decrease from the prior year period was mainly attributable to the Company’s strategic realignment in May 2023, which resulted in reduced clinical development and salaries and benefits expenses. General and administrative expenses were $6.4 million for the year ended March 31, 2024, a decrease of $1.2 million from $7.6 million for the year ended March 31, 2023. The decrease was primarily a result of decreased salaries and benefits due to a reduction in general and administrative headcount as a result of the restructuring and reorganization of our management structure offset by increased legal, tax, accounting and other professional fees related to the restructuring and private placement. At March 31, 2024 the Company had cash and cash equivalents of $23.0 million, as compared to $27.9 million as of March 31, 2023. The Company believes it has sufficient cash to support operations into the second calendar quarter of 2026. About aneurysmal Subarachnoid Hemorrhage (aSAH) aSAH is bleeding over the surface of the brain in the subarachnoid space between the brain and the skull, which contains blood vessels that supply the brain. A primary cause of such bleeding is the rupture of an aneurysm. Approximately 70% of aSAH patients experience death or dependence, and more than 30% die within one month of hemorrhage. Approximately 50,000 patients in the United States are affected by aSAH per year, based on market research. Outside of the United States, annual cases of aSAH are estimated at approximately 60,000 in the European Union, and approximately 150,000 in China. About the Acasti Asset Portfolio GTX-104 is a clinical stage, novel, injectable formulation of nimodipine being developed for intravenous (IV) infusion in aSAH patients to address significant unmet medical needs. The unique nanoparticle technology of GTX-104 facilitates aqueous formulation of insoluble nimodipine for a standard peripheral IV infusion. GTX-104 provides a convenient IV delivery of nimodipine in the Intensive Care Unit potentially eliminating the need for nasogastric tube administration in unconscious or dysphagic patients. Intravenous delivery of GTX-104 also has the potential to lower food effects, drug-to-drug interactions, and eliminate potential dosing errors. Further, GTX-104 has the potential to better manage hypotension in aSAH patients. GTX-104 has been administered in over 150 healthy volunteers and was well tolerated with significantly lower inter- and intra-subject pharmacokinetic variability compared to oral nimodipine. The addressable market in the United States for GTX-104 is estimated to be about $300 million, based on market research. GTX-102 is a novel, concentrated oral-mucosal spray of betamethasone intended to improve neurological symptoms of Ataxia-Telangiectasia (A-T), for which there are currently no FDA-approved therapies. GTX-102 is a stable, concentrated oral spray formulation comprised of the gluco-corticosteroid betamethasone that, together with other excipients can be sprayed conveniently over the tongue of the A-T patient and is rapidly absorbed. The further development of GTX-102 has been deprioritized in favor of our focus on development of GTX-104. It is also possible that we may out-license or sell our GTX-102 drug candidate. GTX-101 is a non-narcotic, topical bio-adhesive film-forming bupivacaine spray designed to ease the symptoms of patients suffering with postherpetic neuralgia (“PHN”). GTX-101 is administered via a metered-dose of bupivacaine spray and forms a thin bio-adhesive topical film on the surface of the patient’s skin, which enables a touch-free, non-greasy application. It also comes in convenient, portable 30 ml plastic bottles. Unlike oral gabapentin and lidocaine patches, we believe that the biphasic delivery mechanism of GTX-101 has the potential for rapid onset of action and continuous pain relief for up to eight hours. No skin sensitivity was reported in a Phase 1 trial. The further development of GTX-101 has been deprioritized in favor of our focus on development of GTX-104. It is also possible that we may out-license or sell our GTX-101 drug candidate. About Acasti Acasti is a late-stage biopharma company with drug candidates addressing rare and orphan diseases. Acasti's novel drug delivery technologies have the potential to improve the performance of currently marketed drugs by achieving faster onset of action, enhanced efficacy, reduced side effects, and more convenient drug delivery. Acasti's lead clinical assets have each been granted Orphan Drug Designation by the FDA, which provides seven years of marketing exclusivity post-launch in the United States, and additional intellectual property protection with over 40 granted and pending patents. Acasti's lead clinical asset, GTX-104, is an intravenous infusion targeting aneurysmal Subarachnoid Hemorrhage (aSAH), a rare and life-threatening medical emergency in which bleeding occurs over the surface of the brain in the subarachnoid space between the brain and skull. For more information, please visit: Forward-Looking Statements Statements in this press release that are not statements of historical or current fact constitute "forward-looking statements" within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, as amended, Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and "forward-looking information" within the meaning of Canadian securities laws (collectively, "forward-looking statements"). Such forward looking statements involve known and unknown risks, uncertainties, and other factors that could cause the actual results of Acasti to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. In addition to statements which explicitly describe such risks and uncertainties, readers are urged to consider statements containing the terms "believes," "belief," "expects," "intends," "anticipates," "estimates", "potential," "should," "may," "will," "plans," "continue", "targeted" or other similar expressions to be uncertain and forward-looking. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. The forward-looking statements in this press release, including statements regarding the Company's anticipated cash runway, the timing of the planned NDA submission with the FDA in connection with the Company's STRIVE-ON trial, GTX-104’s commercial prospects, GTX-104's potential to bring enhanced treatment options to patients suffering from aSAH, and the anticipated benefits and future development, license or sale of the Company's other drug candidates are based upon Acasti's current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including, without limitation: (i) the success and timing of regulatory submissions of the Phase 3 safety trial for GTX-104; (ii) regulatory requirements or developments and the outcome and timing of the proposed NDA application for GTX-104; (iii) changes to clinical trial designs and regulatory pathways; (iv) legislative, regulatory, political and economic developments; and (v) actual costs associated with Acasti's clinical trials as compared to management's current expectations. The foregoing list of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors detailed in documents that have been and are filed by Acasti from time to time with the Securities and Exchange Commission and Canadian securities regulators. All forward-looking statements contained in this press release speak only as of the date on which they were made. Acasti undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by applicable securities laws. For more information, please contact: Acasti Contact: Prashant Kohli Chief Executive Officer Tel: 450-686-4555 Email:info@acastipharma.com Investor Relations: LifeSci Advisors Mike Moyer Managing Director Phone: 617-308-4306 Email: mmoyer@lifesciadvisors.com ---tables to follow--- ACASTI PHARMA INC. Consolidated Balance Sheets March 31, 2024 March 31, 2023 (Expressed in thousands except share data) $ $ Assets Current assets: Cash and cash equivalents 23,005 27,875 Short-term investments — 15 Receivables 722 802 Prepaid expenses 283 598 Total current assets 24,010 29,290 Operating lease right of use asset — 463 Equipment, net 24 104 Intangible assets 41,128 41,128 Goodwill 8,138 8,138 Total assets 73,300 79,123 Liabilities and Shareholders’ equity Current liabilities: Trade and other payables 1,684 3,336 Operating lease liability — 75 Total current liabilities 1,684 3,411 Derivative warrant liabilities 4,359 — Operating lease liability — 410 Deferred tax liability 5,514 7,347 Total liabilities 11,557 11,168 Commitments and contingencies Shareholders’ equity: Class A common shares, no par value per share; unlimited shares authorized; 9,399,404 and 7,435,533 shares issued and outstanding as of March 31, 2024 and 2023, respectively 261,038 258,294 Class B, C, D and E common shares, no par value per share; unlimited shares authorized; none issued and outstanding — — Additional paid-in capital 17,862 13,965 Accumulated other comprehensive loss (6,038 ) (6,038 ) Accumulated deficit (211,119 ) (198,266 ) Total shareholders' equity 61,743 67,955 Total liabilities and shareholders’ equity 73,300 79,123 ACASTI PHARMA INC. Consolidated Statements of Operations and Comprehensive Loss Year ended March 31, 2024 Year ended March 31, 2023 (Expressed in thousands, except share and per data) $ $ Operating expenses Research and development expenses, net of government assistance (4,683 ) (9,972 ) General and administrative expenses (6,432 ) (7,614 ) Sales and marketing (252 ) (661 ) Restructuring cost (1,485 ) — Impairment of intangible assets — (28,682 ) Impairment of goodwill — (4,826 ) Impairment of assets held for sale — (400 ) Loss from operating activities (12,852 ) (52,155 ) Foreign exchange loss (16 ) (72 ) Change in fair value of derivative warrant liabilities (2,728 ) 10 Interest income and other expense, net 911 246 Total other income (expense), net (1,833 ) 184 Loss before income tax benefit (14,685 ) (51,971 ) Income tax benefit 1,832 9,542 Net loss and total comprehensive loss (12,853 ) (42,429 ) Basic and diluted loss per share (1.35 ) (5.71 ) Weighted average number of shares outstanding 9,529,123 7,435,472

Phase 1Financial StatementOrphan DrugPhase 3

28 May 2024

·www.globenewswire.com

Acasti Pharma to Attend BIO International Convention 2024

PRINCETON, N.J., May 28, 2024 (GLOBE NEWSWIRE) -- Acasti Pharma Inc. (Nasdaq: ACST) (Acasti or the Company), a late-stage, biopharma company advancing GTX-104, its novel, injectable formulation of nimodipine that addresses high unmet medical needs for a rare disease, aneurysmal subarachnoid hemorrhage (aSAH), today announced that the Company will be participating in the BIO International Convention taking place at the San Diego Convention Center from June 3-6, 2024. During the conference, Prashant Kohli, Chief Executive Officer of Acasti, will host meetings with pharmaceutical executives to explore partnership and strategic opportunities for the Company’s asset portfolio. To connect during the conference, please request a meeting via the BIO International meeting portal or contact mmoyer@lifesciadvisors.com. About aneurysmal Subarachnoid Hemorrhage (aSAH) aSAH is bleeding over the surface of the brain in the subarachnoid space between the brain and the skull, which contains blood vessels that supply the brain. A primary cause of such bleeding is the rupture of an aneurysm. Approximately 70% of aSAH patients experience death or dependence, and more than 30% die within one month of hemorrhage. Approximately 50,000 patients in the United States are affected by aSAH per year, based on market research. About the Acasti Asset Portfolio GTX-104 is a clinical stage, novel, injectable formulation of nimodipine being developed for intravenous infusion (IV) in aSAH patients to address significant unmet medical needs. The unique nanoparticle technology of GTX-104 facilitates aqueous formulation of insoluble nimodipine for a standard peripheral IV infusion. GTX-104 provides a convenient IV delivery of nimodipine in the Intensive Care Unit potentially eliminating the need for nasogastric tube administration in unconscious or dysphagic patients. Intravenous delivery of GTX-104 also has the potential to lower food effects, drug-to-drug interactions, and eliminate potential dosing errors. Further, GTX-104 has the potential to better manage hypotension in aSAH patients. GTX-104 has been administered in over 150 healthy volunteers and was well tolerated with significantly lower inter- and intra-subject pharmacokinetic variability compared to oral nimodipine. The addressable market in the United States for GTX-104 is estimated to be about $300 million, based on market research. Outside of the United States, annual cases of aSAH are estimated at approximately 60,000 in the European Union, and approximately 150,000 in China. GTX-102 is a novel, concentrated oral-mucosal spray of betamethasone intended to improve neurological symptoms of Ataxia-Telangiectasia (A-T), for which there are currently no FDA-approved therapies. GTX-102 is a stable, concentrated oral spray formulation comprised of the gluco-corticosteroid betamethasone that, together with other excipients can be sprayed conveniently over the tongue of the A-T patient and is rapidly absorbed. GTX-101 is a non-narcotic, topical bio-adhesive film-forming bupivacaine spray designed to ease the symptoms of patients suffering with postherpetic neuralgia (“PHN”). GTX-101 is administered via a metered-dose of bupivacaine spray and forms a thin bio-adhesive topical film on the surface of the patient’s skin, which enables a touch-free, non-greasy application. It also comes in convenient, portable 30 ml plastic bottles. Unlike oral gabapentin and lidocaine patches, we believe that the biphasic delivery mechanism of GTX-101 has the potential for rapid onset of action and continuous pain relief for up to eight hours. No skin sensitivity was reported in a Phase 1 trial. About Acasti Acasti is a late-stage biopharma company with drug candidates addressing rare and orphan diseases. Acasti's novel drug delivery technologies have the potential to improve the performance of currently marketed drugs by achieving faster onset of action, enhanced efficacy, reduced side effects, and more convenient drug delivery. Acasti's lead clinical assets have each been granted Orphan Drug Designation by the FDA, which provides seven years of marketing exclusivity post-launch in the United States, and additional intellectual property protection with over 40 granted and pending patents. Acasti's lead clinical asset, GTX-104, is an intravenous infusion targeting aneurysmal Subarachnoid Hemorrhage (aSAH), a rare and life-threatening medical emergency in which bleeding occurs over the surface of the brain in the subarachnoid space between the brain and skull. For more information, please visit: www.acasti.com. Forward-Looking Statements Statements in this press release that are not statements of historical or current fact constitute "forward-looking statements" within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, as amended, Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and "forward-looking information" within the meaning of Canadian securities laws (collectively, "forward-looking statements"). Such forward looking statements involve known and unknown risks, uncertainties, and other factors that could cause the actual results of Acasti to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. In addition to statements which explicitly describe such risks and uncertainties, readers are urged to consider statements containing the terms "believes," "belief," "expects," "intends," "anticipates," "estimates", "potential," "should," "may," "will," "plans," "continue", "targeted" or other similar expressions to be uncertain and forward-looking. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. The forward-looking statements in this press release, including statements regarding the Company's anticipated cash runway, the timing of the planned NDA submission with the FDA in connection with the Company's STRIVE-ON trial, GTX-104’s commercial prospects, and GTX-104's potential to bring enhanced treatment options to patients suffering from aSAH are based upon Acasti's current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including, without limitation: (i) the success and timing of regulatory submissions of the Phase 3 safety trial for GTX-104; (ii) regulatory requirements or developments and the outcome and timing of the proposed NDA application for GTX-104; (iii) changes to clinical trial designs and regulatory pathways; (iv) legislative, regulatory, political and economic developments; and (v) actual costs associated with Acasti's clinical trials as compared to management's current expectations. The foregoing list of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors detailed in documents that have been and are filed by Acasti from time to time with the Securities and Exchange Commission and Canadian securities regulators. All forward-looking statements contained in this press release speak only as of the date on which they were made. Acasti undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by applicable securities laws. For more information, please contact: Acasti Contact: Prashant KohliChief Executive OfficerTel: 450-686-4555Email: info@acastipharma.comwww.acasti.com Investor Relations: LifeSci AdvisorsMike MoyerManaging DirectorPhone: 617-308-4306Email: mmoyer@lifesciadvisors.com

Clinical ResultPhase 1Orphan Drug

21 May 2024

·www.biospace.com

DURECT Corporation Receives FDA Breakthrough Therapy Designation for Larsucosterol in Alcohol-Associated Hepatitis

DURECT plans to confirm the efficacy and safety of larsucosterol in a registrational Phase 3 clinical trial CUPERTINO, Calif., May 21, 2024 /PRNewswire/ -- DURECT Corporation (Nasdaq: DRRX), a late-stage biopharmaceutical company pioneering the development of epigenetic therapies to transform the treatment of serious and life-threatening conditions such as acute organ injury and cancer, today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation (BTD) to larsucosterol for the treatment of patients with severe alcohol-associated hepatitis (AH). "We're pleased with the FDA's decision to grant Breakthrough Therapy designation to larsucosterol, as it further recognizes its potential to save the lives of AH patients," said James E. Brown, D.V.M., President and CEO of DURECT. "AH has a high mortality rate and no currently approved treatments, so there is a great need for a safe and effective therapy. We continue to finalize the design of our planned registrational Phase 3 trial for larsucosterol, incorporating the recent FDA feedback and promising data from our completed Phase 2b AHFIRM trial. We look forward to releasing additional clinical data on larsucosterol and potentially bringing this therapy to patients as soon as possible." The BTD is supported by clinical evidence from the Phase 2b AHFIRM trial, a double-blind, placebo-controlled, international, multi-center study, which evaluated the safety and efficacy of larsucosterol as a treatment for patients with severe AH. Topline data from the study were announced in 2023, and further details will be shared in a late-breaking oral presentation at the European Association for the Study of the Liver (EASL) Congress 2024 on June 8, 2024 in Milan, Italy. BTD is designed to expedite the development and review of therapies intended to treat a serious or life-threatening condition and whose preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on one or more clinically significant endpoints over existing available therapies. BTD provides therapeutics with all the benefits from a Fast Track designation, such as early and frequent communication with the FDA, eligibility for rolling review and other actions to expedite review, in addition to intensive guidance and organizational commitment involving senior FDA managers. BTD does not change the standards for product approval but may expedite the process. About the AHFIRM Trial AHFIRM was a Phase 2b randomized, double-blind, placebo-controlled, international, multi-center study conducted in subjects with severe alcohol-associated hepatitis (AH) to evaluate the saFety and effIcacy of laRsucosterol treatMent (AHFIRM). The study was comprised of three arms and enrolled 307 patients, with approximately 100 patients in each arm: (1) placebo, which consisted of standard of care, with or without methylprednisolone capsules at the investigators' discretion; (2) larsucosterol (30 mg); and (3) larsucosterol (90 mg). Patients in the larsucosterol arms received the same supportive care without steroids. The primary outcome measure was the 90-Day incidence of mortality or liver transplantation for patients treated with larsucosterol compared to those treated with placebo, and the key secondary endpoint was 90-Day survival. The Company enrolled patients at clinical trial sites across the U.S., EU, U.K., and Australia. Topline data from AHFIRM were announced in November 2023. Reflecting the life-threatening nature of AH and the lack of therapeutic options, the U.S. Food and Drug Administration (FDA) has granted larsucosterol Fast Track designation and Breakthrough Therapy designation for the treatment of AH. For more information, refer to ClinicalTrials.gov Identifier: NCT04563026. About Alcohol-associated Hepatitis (AH) AH is an acute form of alcohol-associated liver disease (ALD) associated with long-term heavy alcohol intake, often following a recent period of increased consumption (i.e., a binge). AH is typically characterized by severe inflammation and liver cell damage, potentially leading to life-threatening complications including liver failure, acute kidney injury and multi-organ failure. There are no FDA approved therapies for AH, and a retrospective analysis of 77 studies published between 1971 and 2016, which included data from 8,184 patients, showed the overall mortality from AH was 26% at 28 days, 29% at 90 days and 44% at 180 days. A subsequent global study published in December 2021, which included 85 tertiary centers in 11 countries across 3 continents, prospectively enrolled 2,581 AH patients with a median Model of End-Stage Liver Disease (MELD) score of 23.5, reported mortality at 28 and 90 days of approximately 20% and 31%, respectively. Stopping alcohol consumption is necessary, but frequently not sufficient for recovery in many moderate (defined as MELD scores of 11-20) and severe (defined as MELD scores >20) patients, and therapies that reduce liver inflammation, such as corticosteroids, are limited by contraindications, have not been shown to improve survival at 90 days or one year, and have demonstrated an increased risk of infection. While liver transplantation is becoming more common for ALD patients, including AH patients, the total number of such transplants is still relatively small and limited by organ availability. Average charges for a liver transplant exceed $875,000, and patients require lifelong immunosuppressive therapy to prevent organ rejection. About Larsucosterol Larsucosterol is an endogenous sulfated oxysterol and an epigenetic modulator. Epigenetic regulators are compounds that regulate patterns of gene expression without modifying the DNA sequence. DNA hypermethylation, an example of epigenetic dysregulation, results in transcriptomic reprogramming and cellular dysfunction, and has been reported in many acute (e.g., AH) and chronic diseases (e.g., MASH). As an inhibitor of DNA methyltransferases (DNMT1, DNMT3a and 3b), larsucosterol inhibits DNA methylation, which subsequently modulates the expression of genes that are involved in cell signaling pathways associated with stress responses, cell death and survival, and lipid biosynthesis. This may ultimately lead to improved cell survival, reduced inflammation, and decreased lipotoxicity. As an epigenetic modulator, the proposed mechanism of action provides further scientific rationale for developing larsucosterol for the treatment of acute organ injury and certain chronic diseases. About DURECT Corporation DURECT is a late-stage biopharmaceutical company pioneering the development of epigenetic therapies that target dysregulated DNA methylation to transform the treatment of serious and life-threatening conditions, including acute organ injury and cancer. Larsucosterol, DURECT's lead drug candidate, binds to and inhibits the activity of DNA methyltransferases (DNMTs), epigenetic enzymes that are elevated and associated with hypermethylation found in alcohol-associated hepatitis (AH) patients. Larsucosterol is in clinical development for the potential treatment of AH, for which the FDA has granted a Fast Track and a Breakthrough Therapy designation; metabolic dysfunction-associated steatohepatitis (MASH) is also being explored. In addition, POSIMIR® (bupivacaine solution) for infiltration use, a non-opioid analgesic utilizing the innovative SABER® platform technology, is FDA-approved and is exclusively licensed to Innocoll Pharmaceuticals for sale and distribution in the United States. For more information about DURECT, please visit and follow us on X (formerly Twitter) at . DURECT Forward-Looking Statements This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, relating to: the potential benefits of Breakthrough Therapy designation, and the potential uses and benefits of laruscosterol in patients with AH and potentially other indications. Actual results may differ materially from those contained in the forward-looking statements contained in this press release, and reported results should not be considered as an indication of future performance. The potential risks and uncertainties that could cause actual results to differ from those projected include, among other things, the risk that future clinical trials of larsucosterol are delayed or do not confirm the results from subset analyses of the AHFIRM trial, including geographic or other segmentation, or of earlier clinical or pre-clinical trials, or do not demonstrate the safety or efficacy of larsucosterol in a statistically significant manner; the risk that the FDA or other government agencies may require additional clinical trials for larsucosterol before approving larsucosterol for the treatment of AH, the risk that Breakthrough Therapy designation does not expedite the process for FDA approval and that larsucosterol may never be approved; risks that Innocoll may not commercialize POSIMIR successfully; and risks related to the sufficiency of our cash resources, our anticipated capital requirements, our need or desire for additional financing, our ability to continue to meet the minimum bid price for continued listing on Nasdaq, our ability to obtain capital to fund our operations and expenses, and our ability to continue to operate as a going concern. Further information regarding these and other risks is included in DURECT's most recent Securities and Exchange Commission (SEC) filings, including its annual report on Form 10-K for the year ended December 31, 2023 and quarterly report on Form 10-Q for the quarter ended March 31, 2024, under the heading "Risk Factors." These reports are available on our website under the "Investors" tab and on the SEC's website at . All information provided in this press release and in the attachments is based on information available to DURECT as of the date hereof, and DURECT assumes no obligation to update this information as a result of future events or developments, except as required by law. NOTE: POSIMIR® is a trademark of Innocoll Pharmaceuticals, Ltd. in the U.S. and a trademark of DURECT Corporation outside of the U.S. SABER® is a trademark of DURECT Corporation. Other referenced trademarks belong to their respective owners. Larsucosterol is an investigational drug candidate under development and has not been approved for commercialization by the U.S. Food and Drug Administration or other health authorities for any indication. Company Codes: NASDAQ-NMS:DRRX

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Indication	Country/Location	Organization	Date
Pain, Postoperative	US	Innocoll Pharmaceuticals Ltd.	28 Aug 2020
Anesthesia	JP	Sandoz KK	03 Sep 1969

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Indication	Highest Phase	Country/Location	Organization	Date
Hernia, Ventral	Phase 3	US	Innocoll Holdings, Inc.	14 Apr 2021
Uterine Neoplasms	Phase 3	US	Innocoll Holdings, Inc.	14 Apr 2021
Hernia, Inguinal	Phase 3	US	Innocoll Pharmaceuticals Ltd.	16 Jun 2017
Bunion	Phase 3	US	Pacira Biosciences, Inc.	01 Apr 2009
Hallux Valgus	Phase 3	US	Pacira Biosciences, Inc.	01 Apr 2009
Pain	Phase 3	US	Pacira Biosciences, Inc.	01 Nov 2008
Hemorrhoids	Phase 3	US	Pacira Biosciences, Inc.	01 Aug 2008
Low Back Pain	Phase 2	US	Pfizer Inc.	01 Mar 2010
Hernia	Phase 2	AU	DURECT Corp.	01 Jan 2007
Hernia	Phase 2	NZ	DURECT Corp.	01 Jan 2007

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04530149 (CTgov)	Phase 4	Rib Fractures \| Pain	3	Acetaminophen+Bupivacain	mpdbterozk(vouyvtnjhu) = fvjlgwnvba qtqehnxfon (qhrbdyntsf, lowjxpcsgh - oovtwrxrlx) View more	-	11 Jun 2024
NCT02865928 (CTgov)	Phase 4	Pain, Postoperative \| Breast Diseases	42	normal saline (Normal Saline)	jtvdbgvcui(qhzmydokfv) = eenfuucsvn irwebepueh (ceiuscyjcz, wrwejfvfjx - wbjumutifn) View more	-	22 Feb 2024
				Bupivicaine HCl (Bupivicaine HCl)	nscthbxbxg(dpamdaymmx) = klnsdotvky kgodeavqgs (iptlgqnemo, jsxxdpbvyk - vhpgojjbip) View more
NCT04826484 (CTgov)	Phase 3	Pain \| Cryptorchidism \| Testicular Hydrocele ... View more	104	Exparel 133 miligrams per 10 milliliter injection+Bupivacaine Hydrochloride (Liposomal Bupivacaine Plus 0.25% Bupivacaine)	adxfmudwlz(lnzqfkpagp) = otnqzbprfu fyktjkwkjo (agmkjmlioq, pnmqcxgcjv - fktbyesmvz) View more	-	26 Dec 2023
				Bupivacaine Hydrochloride (0.25% Bupivacaine Alone)	adxfmudwlz(lnzqfkpagp) = awdhwlkoss fyktjkwkjo (agmkjmlioq, uevxluahbm - fykyqtxqtl) View more
NCT05005260 (CTgov)	Phase 4	occlusions \| Pain, Postoperative	88	Bupivacaine Hcl+Liposomal bupivacaine (Liposomal Bupivacaine Single-shot Interscalene Blockade)	ignyhiayib(lkqswbznwm) = fcyzgcvtdh vuxksnigde (pgyorongga, wuqyzobmcf - jzcrbxtafm) View more	-	18 Dec 2023
				Bupivacaine HCl (Continuous Interscalene Nerve Blockade)	ignyhiayib(lkqswbznwm) = bnwnenkkmq vuxksnigde (pgyorongga, bpyjjccfue - hhmvtvakfe) View more
NCT04897841 (CTgov)	Phase 4	Pain \| complications of cesarean section	60	Bupivacaine Hydrochloride+saline (Control Arm)	dqienbtmvc(eqypytrwyl) = hmgisbbeql lonhluaaqc (rsmfosbyvb, veatscwlgk - frczoykwtq) View more	-	30 Oct 2023
				Bupivacaine Hydrochloride+saline+Liposomal Bupivacaine (Intervention: Liposomal Bupivacaine)	dqienbtmvc(eqypytrwyl) = broqwhqfsd lonhluaaqc (rsmfosbyvb, ytowzpemxn - raegkjyzvm) View more
NCT02513329 (CTgov)	Phase 2	Vasomotor symptom \| Hot Flashes \| Breast Cancer	37	bupivicaine (Bupivicaine)	skwoiqqmsl(hocqjbmque) = txumsjxmmc dfbqxywjhp (jtxgwlaqcu, ftocbugvcv - mguvvhuoyj) View more	-	05 Jun 2023
				Saline (Saline)	skwoiqqmsl(hocqjbmque) = xnfxmlurin dfbqxywjhp (jtxgwlaqcu, fpwnlaaetk - etovoytyly) View more
NCT03702621 (CTgov)	Phase 3	-	90	liposomal Bupivacaine (Liposomal Bupivacaine)	bonzfsovaf(erkegqeasu) = bcskanxhhs fhdroufnxp (enytityiwj, lvezlzhfyb - xpozjjbdnh) View more	-	17 May 2023
				Bupivacaine Hydrochloride (Standard Bupivacaine)	bonzfsovaf(erkegqeasu) = teyhfrunpw fhdroufnxp (enytityiwj, kjwbqaitug - rtadcqlqeb) View more
NCT03122301 (CTgov)	Phase 2	Vasomotor symptom \| Hot Flashes \| Breast Cancer	2	Stellate Ganglion Block injection (Bupivicaine)	acjwiyglzo(nrkpgaoksl) = lehoobibpg nkwxwffpto (mpefbxioyh, qjqnyvumjn - qwhsoajepo) View more	-	03 Jun 2022
				Saline (Saline)	acjwiyglzo(nrkpgaoksl) = nrfomlwgep nkwxwffpto (mpefbxioyh, hyhgwcincv - ntnnwsurcu) View more
NCT04368364 (CTgov)	Phase 4	Pain, Postoperative	3	Intrathecal morphine sulfate (ITM) (Group 1 (Control Group))	thjgyjslnl(jypuwpfycg) = oxugnwybab sxgpunsxeb (rbrxqtdqmx, jfimpzprsq - zjbghqcxzr) View more	-	16 May 2022
				Bupivacaine Hydrochloride (Group 2(Bupivacaine Hydrochloride Group))	thjgyjslnl(jypuwpfycg) = bvuushcbmz sxgpunsxeb (rbrxqtdqmx, fpiirmylhi - rpmhzbrcth) View more
NCT04426500 (CTgov)	Phase 3	Pain, Postoperative	148	Bupivacain (Placebo/Local Anesthesia)	gdbparavxz(novskwxerl) = rrseqjtaca rmklekmnje (erxlmalvtz, tgomvnxdwq - yexciqdnhf) View more	-	06 May 2022
				Ultrasound-guided transversus abdominus plane block+Bupivacain (Ultrasound-guided Transversus Abdominus Plane (UTAP) Block)	gdbparavxz(novskwxerl) = xthtpfvdue rmklekmnje (erxlmalvtz, gyeyhjhrcm - qpxhotzizb) View more

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