Bupivacaine/Meloxicam

A scientist with pill bottles in front of FDA headquarters Taylor Tieden for BioSpace The FDA has six target action dates ahead to round out September as drugs for gastroparesis, Niemann-Pick disease type C and more await decisions. The FDA has several big decision deadlines coming up, including two for blockbuster drugs seeking to push into new indications and one that could potentially open a new mechanism of treatment for schizophrenia. Read below for more. Vanda Proposes Tradipitant to Boost Stomach Emptying By September 18, the FDA is expected to release its verdict on Vanda Pharmaceuticals’ new drug application (NDA) for tradipitant, an investigational NK-1R antagonist the Pennsylvania-based company is proposing for gastroparesis. Afflicting around 6 million people in the U.S., gastroparesis is a serious condition that involves the delayed emptying of the stomach. As a result, patients with gastroparesis suffer from nausea, bloating, fullness after meals, vomiting and abdominal pain. Gastroparesis can also compromise social and occupational functioning. Many cases are undiagnosed. Vanda’s answer to gastroparesis is tradipitant, a small molecule blocker of neurokinin (NK)-1 receptors, which are found in the gastrointestinal tract and in brain regions involved in the vomit reflex. NK-1 receptor antagonists are widely known as anti-emetics , giving tradipitant its potential to suppress the typical nausea and vomiting symptoms that come with gastroparesis. Vanda’s data package for tradipitant includes clinical efficacy studies, data from a 12-week open-label study, evidence from an expanded-access program and non-animal preclinical toxicology data. The FDA previously placed tradipitant under a partial clinical hold , requiring Vanda to provide a standard, nine-month, non-rodent toxicity study before it could treat patients beyond 12 weeks. Aside from gastroparesis, Vanda is also developing tradipitant for motion sickness and atopic dermatitis. Zevra Awaits Verdict on Neimann-Pick Disease Type C Candidate After clearing the FDA’s newly formed Genetic Metabolic Diseases Advisory Committee last month, Zevra Therapeutics is gearing up for the potential approval of its oral drug candidate arimoclomol for Niemann-Pick disease type C (NPC). The FDA’s deadline is September 21. NPC is an ultrarare neurodegenerative lysosomal storage disease characterized by the progressive worsening of physical and cognitive function. The condition arises when mutations in the NPC1 and NPC2 genes impair the otherwise normal transport and clearance of cholesterol and other lipids from inside cells, resulting in the toxic buildup of these molecules in various organs, including the brain. Patients with NPC often suffer from problems with speech, swallowing and movement. The disease is irreversible and can lead to death within months. There are currently no approved therapies for NPC. Arimoclomol addresses NPC by crossing the blood-brain barrier to make nerves more resistant to destruction, even when under stress. A panel of outside experts threw its support behind Zevra , voting 11–5 to recommend arimoclomol’s approval, though pointing out that the drug’s overall benefits seemed small. Heron Awaits FDA’s Go-Ahead for Extended-Release Needle for Zynrelef Heron Therapeutics is proposing a new extended-release solution vial access needle (VAN) for its local anesthetic Zynrelef (bupivacaine and meloxicam). The FDA is expected to release its verdict on or before September 23. VAN is designed to “simplify” the preparation of Zynrelef, according to Heron’s news announcement. The new needle will also lower the withdrawal time for the drug to 20 to 45 seconds, down from the previous duration of up to three minutes. Heron calls VAN a “user-friendly” innovation that could also make Zynrelef safer to administer and increase its uptake. If approved, VAN will replace the vented vial spikes currently deployed for Zynrelef and will be ready for roll-out in the fourth quarter of 2024, according to the biotech’s press release . Zynrelef is a dual-acting local anesthetic that combines the nerve-blocking effects of bupivacaine and the anti-inflammatory activity of the nonsteroidal drug meloxicam. According to its label , Zynrelef was first approved in 2021 and is indicated for post-surgical pain relief after total knee arthroplasty, open inguinal herniorrhaphy and bunionectomy. In Phase III studies, Zynrelef demonstrated significant pain reduction within the first 72 hours after surgery while also increasing the percentage of patients who did not require opioids. Zynrelef comes with a boxed warning for serious cardiovascular and gastrointestinal events, which could become fatal. Merck Tries for Another Keytruda Indication: Pleural Mesothelioma Merck is seeking to add pleural mesothelioma to the ever-growing label of its blockbuster PD-1 inhibitor Keytruda (pembrolizumab). The FDA’s decision is due September 25. Pleural mesothelioma refers to malignancies originating in the membrane that lines the walls of the chest and the lungs. It is a rare malignancy most popularly linked with high exposures to asbestos, and case counts in the U.S. have dropped since the substance was banned in 2000, according to the Cleveland Clinic. Around 3,000 patients are diagnosed with mesothelioma each year, with 80% of cases occurring in the pleura. Merck’s supplemental Biologics License Application (sBLA)—which the FDA accepted and granted Priority Review in May 2024—is backed by data from the pivotal Phase II/III KEYNOTE-483 study. Results showed that Keytruda plus chemotherapy significantly improved overall survival (OS) in patients with unresectable advanced or metastatic malignant pleural mesothelioma, cutting the risk of death by 21% compared with chemotherapy alone. Progression-free survival was also significantly better in the Keytruda plus chemotherapy arm. BMS Awaits Landmark Decision for Schizophrenia Drug KarXT Arguably the FDA’s biggest decision this month is for Bristol Myers Squibb ’s KarXT, an investigational muscarinic antipsychotic being proposed for the treatment of schizophrenia. The regulator’s decision is due September 26. Unlike current treatments for schizophrenia, KarXT works via the dual activation of the M1 and M4 muscarinic receptors and does not directly block dopamine receptors. This unique mechanism of action allows KarXT to ease positive and negative cognitive symptoms in schizophrenia. If approved, KarXT would open up the first new pharmacological treatment approach to schizophrenia in many decades. KarXT was originally developed by Karuna Therapeutics, which BMS acquired in December 2023 for $14 billion . The FDA is currently reviewing BMS’ data package for KarXT, which includes findings from the EMERGENT clinical development program. EMERGENT-1 and EMERGENT-2 , findings from which were released in 2021 and 2022, respectively, established the efficacy of KarXT in treating schizophrenia on the Positive and Negative Syndrome Scale (PANSS). EMERGENT-3 then showed in March 2023 that KarXT could significantly improve overall symptom severity . However, this trial missed a key secondary endpoint and revealed potential cardiovascular risks, spooking investors . In April 2024, BMS unveiled interim findings from the long-term, open-label EMERGENT-4 study, which validated KarXT’s efficacy in schizophrenia, showing that it elicited at least a 30% symptomatic improvement at 52 weeks in more than 75% of treated patients. Sanofi, Regeneron Tee Up COPD Expansion for Dupixent Following a delay in May 2024, the FDA is now nearing its deadline to decide on Sanofi and Regeneron ’s bid to expand the label of their blockbuster treatment Dupixent (dupilumab) into chronic obstructive pulmonary disease (COPD). The regulator’s verdict is due September 27. Dupixent is a fully human monoclonal antibody that targets and blocks the IL-4 and IL-13 pathways, in turn moderating the type 2 inflammatory response. This mechanism of action has won Dupixent several approvals in the space, including for atopic dermatitis, asthma and chronic rhinosinusitis with nasal polyps. Dupixent is not immunosuppressive. The pharma partners are backing Dupixent’s COPD bid with data from the Phase III BOREAS and NOTUS trials. In BOREAS, adding Dupixent to standard of care cut the rate of moderate or severe exacerbations by 30% over 52 weeks, while also boosting lung function and health-related quality of life. Meanwhile, recent data from NOTUS put Dupixent’s efficacy against moderate or severe exacerbations at 34%. In May 2024, the FDA requested additional efficacy analyses from BOREAS and NOTUS. It noted, however, that the follow-up information would constitute a major amendment to Dupixent’s sBLA, thereby requiring a three-month extension to the review period. Sanofi and Regeneron at the time emphasized that the regulator raised no issues about the approvability of Dupixent in COPD.

Second quarter Net Product Sales of $36.0 million, which increased from $31.8 million for the same period in 2023 ZYNRELEF® Vial Access Needle ("VAN") PDUFA goal date set for September 23, 2024 ZYNRELEF included in the proposed 2025 Non-Opioid Policy for Pain Relief ("NOPAIN Act") SAN DIEGO, Aug. 6, 2024 /PRNewswire/ -- Heron Therapeutics, Inc. (Nasdaq: HRTX) ("Heron" or the "Company"), a commercial-stage biotechnology company, today announced financial results for the three and six months ended June 30, 2024, and highlighted recent corporate updates. "We have had an exciting start to 2024 with many encouraging milestones that provide the foundation for ongoing commercial success. We are improving the financial efficiency of the business by growing revenues, improving margins, and reducing expenses. Regarding ZYNRELEF, we continue to expand our partnership with CrossLink and progress our regulatory activities in anticipation of a fourth quarter launch of the VAN," said Craig Collard, Chief Executive Officer of Heron. Business Highlights The range for adjusted operating expenses guidance for 2024 is being narrowed from $108.0 million to $116.0 million to a revised $107.0 million to $111.0 million. Additionally, the range for adjusted EBITDA guidance is being narrowed from $(22.0) million to $3.0 million to a revised $(10) million to $3.0 million. The ZYNRELEF VAN PDUFA goal date is set for September 23, 2024. The VAN is designed to allow for easier and more efficient preparation and administration of ZYNRELEF in the operating room, with anticipated launch before year-end. Our development program for the ZYNRELEF Prefilled Syringe ("PFS"), which will allow for immediate use of ZYNRELEF, continues to progress with an expected U.S. Food and Drug Administration ("FDA") submission for approval in 2026. ZYNRELEF is included in the proposed 2025 NOPAIN Act under the Medicare hospital Outpatient Prospective Payment System ("OPPS") and the Medicare Ambulatory Surgical Center ("ASC") payment system (the "Proposed Rule") as a qualifying product effective April 1, 2025. The Proposed Rule's April 1, 2025 effective date for ZYNRELEF is expected to allow ZYNRELEF to maintain separate reimbursement in the HOPD and ASC settings without disruption. The training and integration of CrossLink sales representatives to promote ZYNRELEF to orthopedic surgeons continues its rapid progress. To date, 561 CrossLink sales representatives have completed training and are building the foundation for increased adoption. Financial Guidance for 2024 The Company narrows its full-year 2024 guidance for Adjusted Operating Expenses and Adjusted EBITDA: Acute Care Franchise Acute Care Franchise Net Product Sales: For the three and six months ended June 30, 2024, acute care franchise Net Product Sales were $6.8 million and $12.3 million, respectively, which increased from $4.5 million and $8.3 million, respectively, for the same period in 2023. ZYNRELEF Net Product Sales: Net Product Sales of ZYNRELEF (bupivacaine and meloxicam) extended-release solution for the three and six months ended June 30, 2024 were $5.8 million and $10.8 million, respectively, which increased from $4.2 million and $7.7 million, respectively, for the same period in 2023. APONVIE® Net Product Sales: Net Product Sales of APONVIE for the three and six months ended June 30, 2024 were $1.0 million and $1.5 million, respectively, which increased from $0.3 million and $0.6 million, respectively, for the same period in 2023. Oncology Care Franchise Oncology Care Franchise Net Product Sales: For the three and six months ended June 30, 2024, oncology care franchise Net Product Sales were $29.2 million and $58.4 million, respectively, which increased from $27.3 million and $53.1 million for the same period in 2023. CINVANTI® Net Product Sales: Net Product Sales of CINVANTI (aprepitant) injectable emulsion for the three and six months ended June 30, 2024 were $24.9 million and $50.5 million, which increased from $24.5 million and $47.3 million for the same period in 2023. SUSTOL® Net Product Sales: Net Product Sales of SUSTOL (granisetron) extended-release injection for the three and six months ended June 30, 2024 were $4.3 million and $7.9 million, respectively, which increased from $2.8 million and $5.8 million, respectively, for the same period in 2023. Conference Call and Webcast Heron will host a conference call and webcast on August 6, 2024 at 4:30 p.m. ET. The conference call can be accessed by dialing (646) 307-1963 for domestic callers and (800) 715-9871 for international callers. Please provide the operator with the passcode 1737564 to join the conference call. The conference call will also be available via webcast under the Investor Relations section of Heron's website at . An archive of the teleconference and webcast will also be made available on Heron's website for sixty days following the call. About ZYNRELEF for Postoperative Pain ZYNRELEF is the first and only dual-acting local anesthetic that delivers a fixed-dose combination of the local anesthetic bupivacaine and a low dose of nonsteroidal anti-inflammatory drug meloxicam. ZYNRELEF is the first and only extended-release local anesthetic to demonstrate in Phase 3 studies significantly reduced pain and significantly increased proportion of patients requiring no opioids through the first 72 hours following surgery compared to bupivacaine solution, the current standard-of-care local anesthetic for postoperative pain control. ZYNRELEF was initially approved by the FDA in May 2021 for use in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after bunionectomy, open inguinal herniorrhaphy and total knee arthroplasty. In December 2021, the FDA approved an expansion of ZYNRELEF's indication to include foot and ankle, small-to-medium open abdominal, and lower extremity total joint arthroplasty surgical procedures. On January 23, 2024, the FDA approved ZYNRELEF for soft tissue and orthopedic surgical procedures including foot and ankle, and other procedures in which direct exposure to articular cartilage is avoided. Safety and efficacy have not been established in highly vascular surgeries, such as intrathoracic, large multilevel spinal, and head and neck procedures. Please see full prescribing information, including Boxed Warning, at . About APONVIE for Postoperative Nausea and Vomiting (PONV) APONVIE is a substance NK1 Receptor Antagonist (RA), indicated for the prevention of PONV in adults. Delivered via a 30-second IV push, APONVIE 32 mg was demonstrated to be bioequivalent to oral aprepitant 40 mg with rapid achievement of therapeutic drug levels. APONVIE is the same formulation as Heron's approved drug product CINVANTI. APONVIE is supplied in a single-dose vial that delivers the full 32 mg dose for PONV. APONVIE was approved by the FDA in September 2022 and became commercially available in the U.S. on March 6, 2023. Please see full prescribing information at . About CINVANTI for Chemotherapy Induced Nausea and Vomiting (CINV) Prevention CINVANTI, in combination with other antiemetic agents, is indicated in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin as a single-dose regimen, delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) as a single-dose regimen, and nausea and vomiting associated with initial and repeat courses of MEC as a 3-day regimen. CINVANTI is an IV formulation of aprepitant, an NK1 RA. CINVANTI is the first IV formulation to directly deliver aprepitant, the active ingredient in EMEND® capsules. Aprepitant (including its prodrug, fosaprepitant) is a single-agent NK1 RA to significantly reduce nausea and vomiting in both the acute phase (0–24 hours after chemotherapy) and the delayed phase (24–120 hours after chemotherapy). The FDA-approved dosing administration included in the U.S. prescribing information for CINVANTI include 100 mg or 130 mg administered as a 30-minute IV infusion or a 2-minute IV injection. Please see full prescribing information at . About SUSTOL for CINV Prevention SUSTOL is indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens. SUSTOL is an extended-release, injectable 5-hydroxytryptamine type 3 RA that utilizes Heron's Biochronomer® drug delivery technology to maintain therapeutic levels of granisetron for ≥5 days. The SUSTOL global Phase 3 development program was comprised of two, large, guideline-based clinical studies that evaluated SUSTOL's efficacy and safety in more than 2,000 patients with cancer. SUSTOL's efficacy in preventing nausea and vomiting was evaluated in both the acute phase (0–24 hours after chemotherapy) and delayed phase (24–120 hours after chemotherapy). Please see full prescribing information at . About Heron Therapeutics, Inc. Heron Therapeutics, Inc. is a commercial-stage biotechnology company focused on improving the lives of patients by developing and commercializing therapeutic innovations that improve medical care. Our advanced science, patented technologies, and innovative approach to drug discovery and development have allowed us to create and commercialize a portfolio of products that aim to advance the standard-of-care for acute care and oncology patients. For more information, visit . Non-GAAP Financial Measures To supplement our financial results presented on a GAAP basis, we have included information about certain non-GAAP financial measures. We believe the presentation of these non-GAAP financial measures, when viewed with our results under GAAP, provide analysts, investors, lenders, and other third parties with insights into how we evaluate normal operational activities, including our ability to generate cash from operations, on a comparable year-over-year basis and manage our budgeting and forecasting. In our quarterly and annual reports, earnings press releases and conference calls, we may discuss the following financial measures that are not calculated in accordance with GAAP, to supplement our consolidated financial statements presented on a GAAP basis. Adjusted EBITDA Adjusted EBITDA is a non-GAAP financial measure that represents GAAP net income or loss adjusted to exclude interest expense, interest income, the benefit from or provision for income taxes, depreciation, amortization, stock-based compensation, and other adjustments to reflect changes that occur in our business but do not represent ongoing operations. Adjusted EBITDA, as used by us, may be calculated differently from, and therefore may not be comparable to, similarly titled measures used by other companies. There are several limitations related to the use of adjusted EBITDA rather than net income or loss, which is the nearest GAAP equivalent, such as: adjusted EBITDA excludes depreciation and amortization and, although these are non-cash expenses, the assets being depreciated or amortized may have to be replaced in the future, the cash requirements for which are not reflected in adjusted EBITDA; we exclude stock-based compensation expense from adjusted EBITDA although: (i) it has been, and will continue to be for the foreseeable future, a significant recurring expense for our business and an important part of our compensation strategy; and (ii) if we did not pay out a portion of our compensation in the form of stock-based compensation, the cash salary expense included in operating expenses would be higher, which would affect our cash position; we exclude impairment of long-lived assets, the amount and/or frequency of which are not part of our underlying business. we exclude inventory write-downs (and write-ups should they occur), the amount and/or frequency of which are not part of our underlying business. adjusted EBITDA does not reflect changes in, or cash requirements for, working capital needs; adjusted EBITDA does not reflect the benefit from or provision for income taxes or the cash requirements to pay taxes; adjusted EBITDA does not reflect historical cash expenditures or future requirements for capital expenditures or contractual commitments; and we exclude restructuring expenses from adjusted EBITDA. Restructuring expenses primarily include employee severance and contract termination costs that are not related to acquisitions. The amount and/or frequency of these restructuring expenses are not part of our underlying business. Adjusted Operating Expenses Adjusted operating expenses is a non-GAAP financial measure that represents GAAP operating expenses adjusted to exclude stock-based compensation expense, depreciation and amortization, and other adjustments to reflect changes that occur in our business but do not represent ongoing operations. The Company has not provided a reconciliation of its full-year 2024 guidance for adjusted EBITDA or adjusted operating expenses to the most directly comparable forward-looking GAAP measures, in reliance on the unreasonable efforts exception provided under Item 10(e)(1)(i)(B) of Regulation S-K, because the Company is unable to predict, without unreasonable efforts, the timing and amount of items that would be included in such a reconciliation, including, but not limited to, stock-based compensation expense, acquisition related expense and litigation settlements. These items are uncertain and depend on various factors that are outside of the Company's control or cannot be reasonably predicted. While the Company is unable to address the probable significance of these items, they could have a material impact on GAAP net income and operating expenses for the guidance period. Forward-looking Statements This news release contains "forward-looking statements" as defined by the Private Securities Litigation Reform Act of 1995. Heron cautions readers that forward-looking statements are based on management's expectations and assumptions as of the date of this news release and are subject to certain risks and uncertainties that could cause actual results to differ materially. Therefore, you should not place undue reliance on forward-looking statements. Examples of forward-looking statements include, among others, statements we make regarding the potential market opportunities for ZYNRELEF, APONVIE, CINVANTI and SUSTOL; revenue, adjusted EBITDA and other financial guidance provided by the Company; the results of the commercial launch of APONVIE; the potential additional market opportunity for the expanded U.S. label for ZYNRELEF or inclusion of ZYNRELEF under the OPPS and the ASC payment system; the timing of the Company's development of the VAN program and receipt of required regulatory approvals; our ability to establish and maintain successful commercial arrangements like our co-promotion agreement with CrossLink Life Sciences; the outcome of the Company's pending ANDA litigation; whether the Company is required to write-off any additional inventory in the future; the expected future balances of Heron's cash, cash equivalents and short-term investments; the expected duration over which Heron's cash, cash equivalents and short-term investments balances will fund its operations and the risk that future equity financings may be needed; any inability or delay in achieving profitability. Important factors that could cause actual results to differ materially from those in the forward-looking statements are set forth in our most recent Annual Report on Form 10-K and any subsequent Quarterly Reports on Form 10-Q, and in our other reports filed with the Securities and Exchange Commission, including under the caption "Risk Factors." Forward-looking statements reflect our analysis only on their stated date, and Heron takes no obligation to update or revise these statements except as may be required by law. Investor Relations and Media Contact: Ira Duarte Executive Vice President, Chief Financial Officer Heron Therapeutics, Inc. [email protected] 858-251-4400 SOURCE Heron Therapeutics, Inc.