Heron Therapeutics Profile
Heron Therapeutics, Inc. operates as a commercial-stage biotechnology company.
The company’s advanced science, patented technologies, and innovative approach to drug discovery and development have allowed it to create and commercialize a portfolio of products that aim to advance the standard of care for acute care and oncology patients.
Acute Care Product Portfolio
ZYNRELEF
ZYNRELEF was initially approved by the U.S. Food and Drug Administration (FDA) in May 2021, and the company commenced commercial sales in the United States (U.S.) in July 2021. In December 2021, the FDA approved its New Drug Application (NDA) for ZYNRELEF, which significantly expanded the indication statement. ZYNRELEF is indicated for use in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after foot and ankle, small-to-medium open abdominal, and lower extremity total joint arthroplasty surgical procedures.
ZYNRELEF is a dual-acting local anesthetic that delivers a fixed-dose combination of the local anesthetic bupivacaine and a low dose of the nonsteroidal anti-inflammatory drug meloxicam. ZYNRELEF is the first and only modified-release local anesthetic to be classified by the FDA as an extended-release product because ZYNRELEF demonstrated 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.
In December 2022, the company submitted an sNDA to the FDA requesting expansion of the indication statement for ZYNRELEF to broadly cover soft tissue and orthopedic surgical procedures. This sNDA is based on safety and pharmacokinetic data from clinical trials in total shoulder arthroplasty, spinal surgery, abdominoplasty, and C-section showing comparable results to the previously completed pivotal safety and efficacy trials of ZYNRELEF. The FDA accepted the sNDA for filing and set a Prescription Drug User Fee Act goal date of October 23, 2023.
In 2022, the company validated large-scale manufacturing of its proprietary polymer and ZYNRELEF, which will allow for the manufacturing of millions of doses of ZYNRELEF annually at a significantly reduced cost of product sales.
In March 2022, CMS approved a 3-year transitional pass-through status of ZYNRELEF, which became effective on April 1, 2022, for separate reimbursement outside of the surgical bundle payment in the Hospital Outpatient Department (HOPD) setting of care. In addition, in December 2022, H.R. 2617, the omnibus spending bill was approved by Congress that includes a provision requiring CMS to pay for certain non-opioids outside the existing bundled payment for surgeries for the period January 1, 2025 through December 31, 2027.
ZYNRELEF was granted a marketing authorization by the European Commission (EC) in September 2020. As of January 1, 2021, ZYNRELEF is approved in 31 European countries, including the countries of the European Union (EU) and the European Economic Area (EEA) and the United Kingdom. ZYNRELEF is indicated in Europe for the treatment of somatic postoperative pain from small- to medium-sized surgical wounds in adults.
Health Canada issued a Notice of Compliance to commercialize ZYNRELEF in March 2022. ZYNRELEF is indicated in Canada for instillation into the surgical wound for postoperative analgesia after bunionectomy, open inguinal herniorrhaphy, and total knee arthroplasty surgical procedures. Based on prior agreements with the FDA, Heron already has clinical studies underway, which the company plans to submit to Health Canada to expand the indication statement.
As the company builds large-scale manufacturing capacity to meet the anticipated commercial demand in the U.S. and the rest of the world, it is developing a coordinated global marketing strategy.
APONVIE (HTX-019)
APONVIE was approved by the FDA in September 2022 and became commercially available in the U.S. in March 2023. APONVIE is indicated for the prevention of postoperative nausea and vomiting (PONV) in adults. CMS granted pass-through payment status for APONVIE, effective April 1, 2023.
APONVIE is the first and only intravenous (IV) formulation of a substance NK1 receptor antagonist indicated for PONV. Delivered via single 30-second IV injection, APONVIE has demonstrated rapid achievement of therapeutic drug levels ideally suited for the surgical setting.
HTX-034
HTX-034, the company’s next-generation product candidate for postoperative pain management, is an investigational non-opioid, fixed-dose combination, extended-release solution of the local anesthetic bupivacaine, the nonsteroidal anti-inflammatory drug meloxicam and aprepitant that further potentiates the activity of bupivacaine. HTX-034 is formulated in the same proprietary polymer as ZYNRELEF. By combining two different mechanisms that each enhance the activity of the local anesthetic bupivacaine, HTX-034 is designed to provide superior and prolonged analgesia. Local administration of HTX-034 in a validated preclinical postoperative pain model resulted in sustained analgesia for 7 days.
In May 2020, the company initiated a Phase 1b/2 clinical study in patients undergoing bunionectomy of HTX-034. The company initiated the expanded Phase 2 portion of the study for HTX-034 in the first quarter of 2021. It has temporarily postponed work on HTX-034 to understand the studies needed for a broad indication for ZYNRELEF, which could impact development planning for HTX-034. The company is pausing the HTX-034 program to focus on the efficacy supplement to further expand the ZYNRELEF indication to broadly include soft tissue and orthopedic surgical procedures.
Oncology Care Product Portfolio
SUSTOL
SUSTOL was approved by the FDA in August 2016, and the company commenced commercial sales in the U.S. in October 2016.
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 (5-HT3) receptor antagonist that utilizes the company’s Biochronomer Technology to maintain therapeutic levels of granisetron for =5 days. The SUSTOL global Phase 3 development program was consisted 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 following chemotherapy) and the delayed phase (24–120 hours following chemotherapy).
SUSTOL is the first extended-release 5-HT3 receptor antagonist approved for the prevention of acute and delayed nausea and vomiting associated with both moderately emetogenic chemotherapy (MEC) and anthracycline and cyclophosphamide (AC) combination chemotherapy regimens. A standard of care in the treatment of breast cancer and other cancer types, AC regimens are among the most commonly prescribed highly emetogenic cancer chemotherapy (HEC) regimens, as defined by both the National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO).
In February 2017, the NCCN included SUSTOL as a part of its NCCN Clinical Practice Guidelines in Oncology for Antiemesis Version 1.2017. The NCCN has given SUSTOL a Category 1 recommendation, the highest-level category of evidence and consensus, for use in the prevention of acute and delayed nausea and vomiting in patients receiving HEC or MEC regimens. The guidelines identify SUSTOL as a preferred agent for preventing nausea and vomiting following MEC. Further, the guidelines highlight the unique, extended-release formulation of SUSTOL.
In January 2018, a product-specific billing code, or permanent J-code (J-code), for SUSTOL became available. The new J-code was assigned by the Centers for Medicare and Medicaid Services (CMS) and has helped simplify the billing and reimbursement process for prescribers of SUSTOL.
CINVANTI
CINVANTI was approved by the FDA in November 2017, and the company commenced commercial sales in the U.S. in January 2018.
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 intravenous (IV) formulation of aprepitant, a substance P/neurokinin-1 (NK1) receptor antagonist. CINVANTI is the first IV formulation to directly deliver aprepitant, the active ingredient in EMEND capsules. Aprepitant (including its prodrug, fosaprepitant) is the only single-agent NK1 receptor antagonist 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). CINVANTI is the first and only IV formulation of an NK1 receptor antagonist indicated for the prevention of acute and delayed nausea and vomiting associated with HEC and nausea and vomiting associated with MEC that is free of synthetic surfactants, including polysorbate 80.
NK1 receptor antagonists are typically used in combination with 5-HT3 receptor antagonists. The only other injectable NK1 receptor antagonist approved in the U.S. for both acute and delayed chemotherapy induced nausea and vomiting (CINV), EMEND IV (fosaprepitant), contains polysorbate 80, a synthetic surfactant, which has been linked to hypersensitivity reactions, including anaphylaxis, and infusion site reactions. The CINVANTI formulation does not contain polysorbate 80 or any other synthetic surfactant. The company’s CINVANTI data has demonstrated the bioequivalence of CINVANTI to EMEND IV, supporting its efficacy for the prevention of both acute and delayed nausea and vomiting associated with HEC and nausea and vomiting associated with MEC. Results also showed CINVANTI was better tolerated in healthy volunteers than EMEND IV, with significantly fewer adverse events (AEs) reported with CINVANTI.
In January 2019, a J-code for CINVANTI became available. The new J-code was assigned by the Centers for Medicare and Medicaid Services (CMS) and has helped simplify the billing and reimbursement process for prescribers of CINVANTI.
In February 2019, the FDA approved the company’s supplemental New Drug Application (sNDA) for CINVANTI, for IV use, which expanded the administration of CINVANTI beyond the initially approved administration method (a 30-minute IV infusion) to include a 2-minute IV injection.
In October 2019, the FDA approved the company’s sNDA for CINVANTI to expand the indication and recommended dosage to include the 130 mg single-dose regimen for patients receiving MEC.
In 2022, the company validated larger-scale manufacturing of CINVANTI.
Biochronomer Technology
The company’s proprietary Biochronomer Technology is designed to deliver therapeutic levels of a wide range of otherwise short-acting pharmacological agents over a period from days to weeks with a single administration. The company’s Biochronomer Technology consists of polymers that have been the subject of comprehensive animal and human toxicology studies that have shown evidence of the safety of the polymer. When administered, the polymers undergo controlled hydrolysis, resulting in a controlled, sustained release of the pharmacological agent encapsulated within the Biochronomer-based composition. Furthermore, the company’s Biochronomer Technology is designed to permit more than one pharmacological agent to be incorporated, such that multimodal therapy can be delivered with a single administration.
Sales and Marketing
The company’s U.S.-based sales and marketing team included 117 employees as of December 31, 2022. The sales and marketing infrastructure includes a targeted, acute care and oncology sales force to establish relationships with a focused group of surgeons, oncologists, nurses and pharmacists. Additionally, the commercial team manages relationships with key accounts, such as managed care organizations, group purchasing organizations, hospital systems, oncology group networks, payors and government accounts. The sales force is supported by sales management, internal sales support, an internal marketing group and distribution support.
Customers
The company’s Products (CINVANTI, SUSTOL and ZYNRELEF (collectively, the company’s ‘Products’)) are distributed in the U.S. through a limited number of specialty distributors and full line wholesalers (collectively, Customers) that resell to healthcare providers and hospitals, the end users of its Products.
Research and Development
For the year ended December 31, 2022, the company’s research and development expense was $107.5 million.
Intellectual Property
The company has filed a number of U.S. patent applications on inventions relating to the composition of a variety of polymers, specific products, product groups and processing technology. As of December 31, 2022, the company had a total of 33 issued U.S. patents and an additional 111 issued (or registered) foreign patents. The patents on the bioerodible technologies expire in March 2026. CINVANTI is covered by 9 patents issued in the U.S. and by three patents issued (or registered) in foreign countries, including Korea and Japan. The U.S. patents covering CINVANTI have expiration dates ranging from September 2035 to February 2036; foreign patents covering CINVANTI have expiration dates ranging from September 2035 to February 2036. SUSTOL is covered by 6 patents issued in the U.S. and by 18 patents issued (or registered) in foreign countries, including France, Germany, Hong Kong, Ireland, Italy, Japan, Spain, Sweden, Switzerland, Taiwan, and the United Kingdom. The U.S. patents covering SUSTOL expire in September 2024; foreign patents covering SUSTOL expire in September 2025. ZYNRELEF is protected by 15 patents issued in the U.S. and by 89 patents issued (or registered) in foreign countries, including Albania, Australia, Austria, Belgium, Bulgaria, Canada, Croatia, Cyprus, the Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hong Kong, Hungary, Iceland, Ireland, Italy, Japan, Korea, Latvia, Lithuania, Luxembourg, Macedonia, Malta, Mexico, Monaco, the Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Taiwan, Turkey and the United Kingdom. The U.S. patents covering ZYNRELEF have expiration dates ranging from March 2034 to April 2035; foreign patents covering ZYNRELEF have expiration dates ranging from November 2033 to November 2036. APONVIE is covered by 9 patents issued in the U.S. and by three patents issued (or registered) in foreign countries, including Korea and Japan. The U.S. patents covering APONVIE have expiration dates ranging from September 2035 to February 2036; foreign patents covering APONVIE have expiration dates ranging from September 2035 to February 2036. HTX-034 is protected by 12 patents issued in the U.S. and by 89 patents issued (or registered) in foreign countries, including Albania, Australia, Austria, Belgium, Bulgaria, Canada, Croatia, Cyprus, the Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hong Kong, Hungary, Iceland, Ireland, Italy, Japan, Korea, Latvia, Lithuania, Luxembourg, Macedonia, Malta, Mexico, Monaco, the Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Taiwan, Turkey and the United Kingdom. The U.S. patents covering HTX-034 have expiration dates ranging from March 2034 to April 2035; foreign patents covering HTX-034 have expiration dates ranging from November 2033 to November 2036.
Government Regulation
The company’s manufacturing and processing agreements require that all third-party contract manufacturers and processors produce active pharmaceutical ingredients, excipients and finished products in accordance with the FDA’s current Good Manufacturing Practices (cGMP) and all other applicable laws and regulations.
In addition, both before and after approval is sought, the company is required to comply with a number of FDA requirements. For example, the company is required to report certain adverse reactions and production problems, if any, to the FDA, and to comply with certain limitations and other requirements concerning advertising and promotion for its products.
The company’s research and development processes involve the controlled use of hazardous materials, including chemicals. Some of these hazardous materials are considered to be controlled substances and subject to regulation by the U.S. Drug Enforcement Agency (DEA). The company must be registered by the DEA in order to engage in these activities, and it is subject to periodic and ongoing inspections by the DEA and similar state drug enforcement authorities to assess ongoing compliance with the DEA’s regulations.
The company is subject to the Foreign Corrupt Practices Act of 1997 (FCPA). The company is subject to a variety of financial disclosure and securities trading regulations as a public company in the U.S., including laws relating to the oversight activities of the U.S. Securities and Exchange Commission (SEC) and the regulations of The Nasdaq Capital Market, on which its shares are traded.
History
The company was founded in 1983. It was incorporated in 1987. The company was formerly known as AMCO Polymerics, Inc. and changed its name to Advanced Polymer Systems, Inc. in 1984 and then to A.P. Pharma, Inc. in 2001. Further, the company changed its name to Heron Therapeutics, Inc. in 2014.
