Omadacycline Tosylate

BOSTON, May 21, 2025 (GLOBE NEWSWIRE) -- Paratek Pharmaceuticals, Inc., a privately held pharmaceutical company focused on the development and commercialization of specialty therapies for specialists and community care providers, that address important medical and public health threats, today announced that the Company has completed its acquisition of Optinose, Inc. (NASDAQ:OPTN). This acquisition broadens Paratek’s commercial portfolio which now includes both its flagship antibiotic, NUZYRA® (omadacycline), and Optinose’s product XHANCE® (fluticasone propionate). “Adding XHANCE to our portfolio is a pivotal first step in achieving our long-term vision to become a multi‑product specialty therapeutics company, focused on addressing significant unmet medical needs,” said Evan Loh, MD, Chief Executive Officer of Paratek. “Our medical and commercial teams are deeply experienced with capabilities focused on bringing innovative treatments to specialists and primary care providers that address the needs of their patients. This transaction establishes a strong platform for us to continue to leverage these capabilities as we move forward to explore opportunities to expand our portfolio through future product acquisitions.” Under the terms of the merger agreement, Paratek acquired all outstanding shares of Optinose for approximately $330 million, including the assumption of debt and assuming full payment of the contingent value rights (CVRs), and Optinose shareholders were paid $9 per share in cash and received CVRs for up to $5 per share in cash payable in the event that certain net revenue milestones are achieved by XHANCE. Paratek will pay $1 per share if XHANCE achieves $150M in net sales in any calendar year prior to December 31, 2028, and $4 per share if XHANCE achieves $225M in net sales in any calendar year prior to December 31, 2029. Optinose shareholders approved the merger proposal at Optinose’s special meeting of shareholders held on May 16, 2025, and following completion of the merger Optinose's common stock will be delisted from the Nasdaq Global Select Market. The transaction was financed with capital from Paratek, B-FLEXION Life Sciences, and Novo Holdings, and debt financing from funds managed by Oaktree Capital Management, L.P. ("Oaktree"). Lazard acted as the exclusive financial advisor to Paratek Pharmaceuticals, and Skadden, Arps, Slate, Meagher & Flom LLP served as its legal advisor. Evercore acted as the exclusive financial advisor to Optinose, and Hogan Lovells US LLP served as its legal advisor. About Paratek Pharmaceuticals, Inc.Paratek Pharmaceuticals, Inc. is a privately held pharmaceutical company providing innovative specialty therapies for specialists and community care providers, addressing important medical and public health threats. Paratek's lead product, NUZYRA (omadacycline), is a once-daily oral and intravenous antibiotic indicated for adults with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI). Paratek continues to diversify its portfolio to address unmet patient needs. Paratek was acquired in 2023 by B-FLEXION and Novo Holdings. For more information, visit https://www.paratekpharma.com/ or follow us on LinkedIn and X. About B-FLEXION Life SciencesB-FLEXION Life Sciences is part of the B-FLEXION group, a private, entrepreneurial investment firm with offices in Europe and the United States. B-FLEXION seeds, acquires and builds investment partnerships across a number of focused fields and makes principal investments into operating businesses in transformative industries. Through B-FLEXION Life Sciences there is also targeted investment across biopharma, diagnostics and a broad spectrum of innovative healthcare services. It is an active owner, applying the experience and skills of its investment and operationally experienced team to work closely with management to build its portfolio companies. www.bflexion.com About Novo Holdings A/SNovo Holdings is a holding and investment company that is responsible for managing the assets and the wealth of the Novo Nordisk Foundation. The purpose of Novo Holdings is to improve people’s health and the sustainability of society and the planet by generating attractive long-term returns on the assets of the Novo Nordisk Foundation. Wholly owned by the Novo Nordisk Foundation, Novo Holdings is the controlling shareholder of Novo Nordisk and Novonesis and manages an investment portfolio with a long-term return perspective. In addition to managing a broad portfolio of equities, bonds, real estate, infrastructure and private equity assets, Novo Holdings is a world-leading life sciences investor. Through its Seed, Venture, Growth, Planetary Health Investments and Principal Investments teams, Novo Holdings invests in life science companies at all stages of development. As of year-end 2024, Novo Holdings had total assets of EUR 142 billion. www.novoholdings.dk About OaktreeOaktree is a leader among global investment managers specializing in alternative investments, with $203 billion in assets under management as of March 31, 2025. The firm emphasizes an opportunistic, value-oriented, and risk-controlled approach to investments in credit, equity, and real estate. The firm has more than 1,200 employees and offices in 25 cities worldwide. For additional information, please visit Oaktree’s website at http://www.oaktreecapital.com/. About NUZYRANUZYRA (omadacycline) is an antibiotic with both once-daily oral and intravenous (IV) formulations indicated for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible microorganisms. A next-generation tetracycline, NUZYRA is specifically designed to overcome tetracycline resistance and exhibits activity across a spectrum of bacteria, including Gram-positive, Gram-negative, atypical, and other drug-resistant strains. IMPORTANT SAFETY INFORMATIONCONTRAINDICATIONSNUZYRA is contraindicated in patients with known hypersensitivity to omadacycline or tetracycline-class antibacterial drugs or to any of the excipients. WARNINGS AND PRECAUTIONSMortality imbalance was observed in the CABP clinical trial with eight deaths (2%) occurring in patients treated with NUZYRA compared to four deaths (1%) in patients treated with moxifloxacin. The cause of the mortality imbalance has not been established. All deaths, in both treatment arms, occurred in patients > 65 years of age; most patients had multiple comorbidities. The causes of death varied and included worsening and/or complications of infection and underlying conditions. Closely monitor clinical response to therapy in CABP patients, particularly in those at higher risk for mortality. The use of NUZYRA during tooth development (last half of pregnancy, infancy and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown) and enamel hypoplasia.The use of NUZYRA during the second and third trimester of pregnancy, infancy and childhood up to the age of 8 years may cause reversible inhibition of bone growth. Hypersensitivity reactions have been reported with NUZYRA. Life-threatening hypersensitivity (anaphylactic) reactions have been reported with other tetracycline-class antibacterial drugs. NUZYRA is structurally similar to other tetracycline-class antibacterial drugs and is contraindicated in patients with known hypersensitivity to tetracycline-class antibacterial drugs. Discontinue NUZYRA if an allergic reaction occurs. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs. NUZYRA is structurally similar to tetracycline-class antibacterial drugs and may have similar adverse reactions. Adverse reactions, including photosensitivity, fixed drug eruption, pseudotumor cerebri, and anti-anabolic action (which has led to increased BUN, azotemia, acidosis, hyperphosphatemia, pancreatitis, and abnormal liver function tests), have been reported for other tetracycline-class antibacterial drugs, and may occur with NUZYRA. Discontinue NUZYRA if any of these adverse reactions are suspected. Prescribing NUZYRA in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. ADVERSE REACTIONSThe most common adverse reactions (incidence 2%) are nausea, vomiting, infusion site reactions, alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyl transferase increased, hypertension, headache, diarrhea, insomnia, and constipation. DRUG INTERACTIONSPatients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage while taking NUZYRA. Absorption of tetracyclines, including NUZYRA is impaired by antacids containing aluminum, calcium, or magnesium, bismuth subsalicylate and iron containing preparations. USE IN SPECIFIC POPULATIONSLactation: Breastfeeding is not recommended during treatment with NUZYRA. See full prescribing information here. About XHANCEXHANCE is a drug-device combination product that uses the Exhalation Delivery System™ (also known as the EDS®) designed to deliver a topical steroid to the high and deep regions of the nasal cavity where sinuses ventilate and drain. XHANCE is approved by the U.S. Food and Drug Administration for both the treatment of chronic rhinosinusitis without nasal polyps (also called chronic sinusitis) and chronic rhinosinusitis with nasal polyps (also called nasal polyps) in patients 18 years of age or older. IMPORTANT SAFETY INFORMATIONCONTRAINDICATIONS: Hypersensitivity to any ingredient in XHANCE.WARNINGS AND PRECAUTIONS: Local nasal adverse reactions, including epistaxis, erosion, ulceration, septal perforation, Candida albicans infection, and impaired wound healing, can occur. Monitor patients periodically for signs of possible changes on the nasal mucosa. Avoid use in patients with recent nasal ulcerations, nasal surgery, or nasal trauma until healing has occurred.Glaucoma and cataracts may occur with long-term use. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use XHANCE long-term.Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, contact dermatitis, rash, hypotension, and bronchospasm) have been reported after administration of fluticasone propionate. Discontinue XHANCE if such reactions occur.Immunosuppression and infections can occur, including potential increased susceptibility to or worsening of infections (e.g., existing tuberculosis; fungal, bacterial, viral, or parasitic infection; ocular herpes simplex). Use with caution in patients with these infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients.Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue XHANCE slowly.Assess for decrease in bone mineral density initially and periodically thereafter. ADVERSE REACTIONS: Chronic rhinosinusitis without nasal polyps: The most common adverse reactions (incidence 3%) are epistaxis, headache, and nasopharyngitis.Chronic rhinosinusitis with nasal polyps: The most common adverse reactions (incidence 3%) are epistaxis, nasal septal ulceration, nasopharyngitis, nasal mucosal erythema, nasal mucosal ulcerations, nasal congestion, acute sinusitis, nasal septal erythema, headache, and pharyngitis. DRUG INTERACTIONS: Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. May increase risk of systemic corticosteroid effects. USE IN SPECIFIC POPULATIONS: Hepatic impairment. Monitor patients for signs of increased drug exposure. See full prescribing information here. MEDIA CONTACT: Adam Silversteinadam@scientpr.com

前言2025年5月16日，苑东生物子公司青木制药申报的甲苯磺酸奥马环素原料药获CDE受理，成为国内首家仿制该品种的企业。这一突破不仅填补了国产耐药抗生素领域的空白，更标志着我国在高端原料药研发上迈出关键一步。作为新一代广谱抗生素，奥马环素凭借其强效抗耐药特性，被全球视为对抗“超级细菌”的利器。国产化后，药物可及性将大幅提升，患者负担有望显著降低。这不仅是技术的胜利，更是中国医药创新政策与临床需求深度联动的缩影。从米诺环素到抗耐药 “利器”米诺环素作为第二代四环素类抗生素 ，通过可逆性结合细菌核糖体 30S 亚基，阻止氨酰基 - tRNA 与 mRNA - 核糖体复合物受体部位结合，从而抑制细菌蛋白合成，对革兰阳性菌和阴性菌、支原体、衣原体和立克次体等均具抗菌活性。然而，随着临床的广泛使用，细菌逐渐对其产生耐药性，限制了米诺环素的疗效。奥马环素在米诺环素的基础上，进行了关键的 C9 位氨甲基修饰。这一修饰看似微小，却带来了一系列显著的变化。从克服耐药性的角度来看，细菌对四环素类药物产生耐药的重要机制之一是核糖体保护机制，由核糖体保护蛋白基因 TetO 介导 ，它会改变核糖体构象，使四环素类药物难以与核糖体结合，从而逃逸药物对蛋白合成的抑制作用。而奥马环素的 C9 位氨甲基修饰，能够有效克服这一机制，让药物重新恢复与核糖体 30S 亚基的结合能力，保证了对细菌蛋白质合成的抑制，进而发挥抗菌作用。从抗菌谱的角度分析，修饰后的奥马环素抗菌谱得到了极大的扩展。它不仅对常见的革兰氏阳性菌、革兰氏阴性菌具有良好的抗菌活性，还对衣原体、支原体、脲原体属、快速生长分枝杆菌等非典型病原体，以及脆弱拟杆菌、拟杆菌、产气荚膜梭状芽胞杆菌、艰难梭菌等厌氧菌均具良好抗菌活性。相比之下，米诺环素虽然也有较广的抗菌谱，但在面对一些耐药菌和特殊病原体时，效果远不如奥马环素。奥马环素的 C9 位氨甲基修饰还改善了药代动力学特性。它增强了口服生物利用度，使得药物在口服后能够更好地被人体吸收，进入血液循环，到达感染部位发挥作用。相关研究表明，奥马环素口服生物利用度可达 34.5%，这一数据为其在临床治疗中的广泛应用提供了有力支持。在对超级细菌的抑制作用上，奥马环素表现尤为出色。以耐甲氧西林金黄色葡萄球菌（MRSA）为例，多项临床研究和实验数据证实了奥马环素的强效抑制能力。在 2017 - 2018 年开展的 OASIS-1 和 OASIS-2 这两项随机、双盲、多中心 Ⅲ 期临床研究中，共纳入 1390 例急性细菌性皮肤及皮肤结构感染（ABSSSI）成年患者，对比了奥马环素与利奈唑胺的疗效与安全性。结果显示，在 OASIS-2 研究中，奥马环素组对金黄色葡萄球菌（包括 MRSA）感染的临床治愈率达到 82.7％ ，与利奈唑胺组的 79.8％相仿或略优。这充分证明了奥马环素在应对 MRSA 感染时的有效性，为临床治疗 MRSA 引起的各类感染提供了新的有力武器。从 “临床急需” 到医保覆盖2017 年，中国国家药品监督管理局实施了一项意义深远的政策 —— 优先审评审批制度。这一制度旨在为临床急需、具有显著治疗优势的创新药和仿制药开辟一条 “绿色通道”，加速它们的上市进程。该制度明确规定，符合特定条件的药物可纳入优先审评通道：防治严重危及生命的疾病且尚无有效治疗手段的药物，比如一些针对罕见病且目前无有效治疗方案的新药；公共卫生急需的疫苗或防控重大传染病的药物，在面对突发公共卫生事件时，相关疫苗和药物能够快速获批，为疫情防控争取时间；临床优势明显的创新药或改良型新药，这些药物相较于现有治疗手段，在疗效、安全性等方面有显著提升；列入《临床急需境外新药名单》的品种，能快速进入国内市场，满足患者对先进治疗药物的需求。奥马环素，作为新一代广谱抗生素，凭借其独特的抗菌机制和对多重耐药菌的强大抑制作用，精准契合了我国对抗菌药物创新的迫切需求。因此，它被列入《临床急需境外新药名单（第二批）》 。2021 年，甲苯磺酸奥马环素获国家药品监督管理局批准上市，用于治疗社区获得性细菌性肺炎（CABP）和急性细菌性皮肤及皮肤结构感染（ABSSSI）。值得一提的是，从新药上市申请（NDA）提交到最终获批，仅仅耗时 8 个月。在进入医保覆盖方面，奥马环素也稳步前行。2022 年，甲苯磺酸奥马环素静脉输注剂型通过医保谈判，成功被纳入国家医保药品目录，用于治疗社区获得性细菌性肺炎和急性细菌性皮肤和皮肤结构感染。这一举措使得更多患者能够在医保的支持下，用上这款新型抗生素。2023 年，甲苯磺酸奥马环素口服剂型也被纳入医保目录，用于治疗社区获得性细菌性肺炎（CABP）和急性细菌性皮肤和皮肤结构感染（ABSSSI）成人患者 。到了 2024 年，静脉输注剂型成功续约国家医保药品目录，持续为患者提供保障。政策的推动作用不言而喻。优先审评审批制度让奥马环素快速获批上市，缩短了患者等待新药的时间，使临床医生能够及时使用新的抗菌药物应对耐药菌感染。医保覆盖进一步降低了患者的用药成本，提高了药物的可及性，让更多社区获得性细菌性肺炎和急性细菌性皮肤及皮肤结构感染患者能够受益于奥马环素的治疗，对于控制感染性疾病的传播、提高患者治愈率和生活质量都有着积极而深远的意义。技术破壁与市场潜力双赢奥马环素的合成工艺因化学结构复杂性和反应条件严苛性，长期被视为国内原料药研发的技术难点。其C9位氨甲基修饰对合成路径的选择性、中间体纯度及最终产物质控均提出较高要求。苑东生物基于在复杂原料药合成领域的经验，通过优化关键中间体制备工艺，解决了传统方法收率低、杂质多的问题。例如，在C9位修饰步骤中，团队通过筛选新型催化剂和改进反应体系，将中间体纯度从85%提升至98%以上。此外，通过模块化工艺设计，实现了各合成环节的高效衔接，最终完成原料药的规模化生产。2025年5月，其甲苯磺酸奥马环素原料药获CDE受理，标志着国产化进程迈出关键一步。国产原料药的突破将推动制剂成本下降。根据行业分析，进口奥马环素注射剂单支价格约为2000元，而国产化后预计可降至1000-1400元，降幅达30%-50%。这一变化有望减轻患者经济负担，同时提升医保资金使用效率。市场层面，公开资料显示，2022-2024年奥马环素在华销售额从520万美元增至4320万美元，年复合增长率超100%。2025年第一季度销售额达1510万美元，同比增长52%，反映临床需求的快速增长。随着国产原料药及制剂的上市，本土企业或将通过成本优势进一步扩大市场份额。结语苑东生物在甲苯磺酸奥马环素上的首仿突破，不仅是技术实力的彰显，更是一场关乎民生健康的攻坚战。国产化意味着中国在高端抗生素领域不再受制于人，也为全球耐药危机提供了“中国方案”。参考：CDE官网；苑东生物官网药事纵横投稿须知：稿费已上调，欢迎投稿