Somatropin (genetical recombination)(JCR)

关注并星标CPHI制药在线3月8日，维昇药业（VISEN Pharmaceuticals）宣布中国国家药品监督管理局（NMPA）已受理隆培促生长素（lonapegsomatropin，Skytrofa）的上市许可申请（BLA）。隆培促生长素是第一个在欧美获批上市的长效生长激素，每周注射一次，用于治疗儿童生长激素缺乏症。       隆培促生长素是采用全球极具创新性的TransConTM（Transient Conjugation, 暂时连接）专利技术平台设计的人生长激素前药，能够以可控的方式在体内缓慢释放未经修饰的生长激素，血浆半衰期可达30.7（±12.7）小时，支持每周一次给药。       已公布的隆培促生长素针对中国生长激素缺乏症（GHD）儿童患者的3期临床试验数据显示：治疗52周时，隆培促生长素治疗组儿童生长激素缺乏症患者的年化生长速率（AHV）显著高于生长激素日制剂组（10.66厘米/年Vs 9.75厘米/年），达到研究主要终点。       此外，在52周治疗期间，隆培促生长素治疗组和生长激素日制剂组患者的平均胰岛素样生长因子-1（IGF -1）标准差积分(SDS)均增加至正常范围内，且隆培促生长素组相对较高。IGF -1是肝脏对生长激素反应时产生的一种多肽，可刺激软骨细胞增殖、分化和胶原的合成。而且，隆培促生长素耐受性良好，安全性与生长激素日制剂相当。       隆培促生长素由Ascendis Pharma开发，维昇药业拥有其在大中华区的独家开发、制造和商业化权益。2021年8月，该药被FDA用于治疗年龄在一岁及以上、体重至少11.5公斤、因内源性生长激素分泌不足而导致生长迟缓的儿童患者。2022年1月，该药在欧盟被批准用于治疗因内源性生长激素分泌不足而导致的3-18岁儿童和青少年生长迟缓。据公司财报，隆培促生长素2022年、2023年销售额分别为35百万欧元和179百万欧元，预计2024年将达到320-340百万欧元。       生长激素药物的发展迭代       生长激素缺乏症（GHD），又称垂体性侏儒，因下丘脑-垂体轴的器质性病变或是功能性异常导致生长激素缺乏引起，患者不仅表现为身材矮小，还存在代谢异常、心理社会挑战、认知缺陷和生活质量差等问题。据公开资料，我国儿童患矮小症的比例约为3%，其中GHD最为常见，占比约三分之一。补充生长激素是目前公认治疗儿童GHD最有效方法之一。       生长激素是人脑垂体前叶嗜酸性细胞分泌的一种长度为191个氨基酸的肽类 激素，通过刺激肝脏等组织产生胰岛素样生长因子（IGF -1）发挥生理功能，促进骨骼生长，促进蛋白质合成，调节脂肪、糖、矿物质代谢等，在人体生长发育过程中发挥重要作用。       根据制备技术的迭代，生长激素药物的研发经历了五代更替。其中第一代生长激素从人脑垂体中提取，存在来源受限、传递传染性疾病的风险，且会引起慢性脑部海绵样变性导致死亡，世界各国已相继停用。第二代生长激素是利用大肠杆菌包涵体技术合成的基因重组人生长激素（rhGH），与天然生长激素结构不同，由192个氨基酸组成，但容易产生抗体影响疗效，目前已淘汰。第三代生长激素是利用普通大肠杆菌以及哺乳动物真核表达系统，表达合成的含有191个氨基酸的 rhGH ，结构与hGH还有差异，存在易产生抗体、成本高和易污染等缺点。第四代生长激素是利用哺乳动物细胞重组DNA技术合成的含有191个氨基酸的生长激素，其结构和天然的生长激素结构更为接近，目前仅被极少数生产厂家沿用。第五代生长激素是利用分泌型大肠杆菌表达技术合成，其氨基酸含量、序列和蛋白质结构与人垂体生长激素完全一致，因此生物活性高、免疫原性低、副作用少。       剂型上，目前市面上的生长激素产品包括短效粉针、短效水针和长效水针，其中粉针粉针和短效水针在疗效上没有显著差异，但针粉临床使用繁琐，注射前需抽取抑菌水注入冻干粉容器中重新配制，不过其稳定性较水针好。       金赛药业领跑，国内多款生长激素产品获批上市       目前，国内已批准多款生长激素产品，详见下表。整体来看，国内生长激素持有企业比较集中，主要为金赛药业、安科生物等。其中金赛药业是国内生长激素的领军企业，且是国内唯一实现短效粉针、短效水针、长效水针三种剂型全部上市的企业。       据米内网数据，2022年中国城市公立医院、县级公立医院、城市社区中心以及乡镇卫生院（简称中国公立医疗机构）终端生长激素销售规模约为67亿元，其中金赛药业是行业老大，市场占比超80%：在粉针剂市场，金赛药业市场份额占比超50%；在水针剂市场，金赛药业市场份额高达99%；金赛增是国内唯一获批的长效水针，2022年销售额超7亿元。       对比国外，国内批准的长效生长激素水针有限，仅金赛药业的金赛增。目前，国外已批准多款长效生长激素水针，即Ascendis Pharma的Skytrofa、诺和诺德的Sogroya和辉瑞的Ngenla。       上述四款长效生长激素的长效作用机制还不太一样。其中Skytrofa是凭借TransCon技术，该技术可使其给药后以可控方式在一周内缓慢释放未经修饰的活性生长激素，从而发挥作用。Sogroya是一种hGH的长效类似物，由天然的hGH经过修饰以增强其与血浆白蛋白的结合，使其适合每周一次给药。Ngenla也是一种长效hGH类似物，利用OPKO专有的C末端肽段（CTP）长效技术在一段天然生长激素序列的C和N末端分别加上了2个和1个来自人类绒毛膜促性腺激素（HCG）β亚基的CTP拷贝，使其半衰期得以延长。金赛增是全球首支上市的聚乙二醇（PEG）化长效生长激素注射液，其利用天然肽键连接了惰性PEG和天然结构的生长激素，从而降低其被肾脏过滤的速度和蛋白酶对它的降解作用，进而提高其在人体内的稳定性。       此外，微球技术也被开发用长效生长激素领域，如基因泰克的Nutropin Depot、韩国LG Life Sciences的 Declage。其中Nutropin Depot是全球第一个上市的长效生长激素，其采用PLGA缓释微球技术，缓释效果显著，1999年获批上市，但后续因注射局部疼痛，4年后退市。Declage采用的是透明质酸技术，2007年在韩国上市。       长效生长激素有哪些后备军       长效生长激素是儿童GHD生长激素替代疗法研发的热门方向，目前全球药企已研发出多款在研长效生长激素，详见下表。我国药企也积极布局长效生长激素，其中特宝生物的怡培生长激素已于今年1月在国内报产。       怡培生长激素由特宝生物自主研发，其采用40kD Y型分支聚乙二醇（YPEG）分子对rhGH进行单分子修饰，优选高生物学活性、非N-末端位点为主的修饰组分，在保证疗效的同时，旨在降低给药剂量，获得更佳的长期药物安全性。已公布的2/3期研究数据显示：儿童GHD患者接受12周治疗后，怡培生长激素100、120、140μg/kg/周组和重组人生长激素35μg/kg/天组（对照组）的身高增长速度分别为7.07、10.39、12.27厘米/年和11.58厘米/年。       天境生物的伊坦生长激素进展也相对较快，其治疗儿童GHD的3期研究已达到非劣效性主要终点，今年将递交上市申请。该药是基于Genexine的专利hyFc®技术开发，hyFc部分由人 免疫球蛋白D（IgD）和G4（IgG4）的一部分组成。前者包含一个柔性铰链，后者可通过新生儿Fc受体（FcRn）介导的代谢调控延长半衰期。已公布的3期临床试验结果显示：伊坦生长激素组患者的年化身高生长速率（AHV）为10.76厘米/年，而Norditropin（诺泽）组患者的AHV为10.28厘米/年。       值得一提的是，围绕伊坦生长激素药企间达成数项交易。该药由Genexine开发，2015年10月天士力子公司Tasgen（被天境生物收购）与Genexine达成协议，获得伊坦生长激素的中国权益。2021年11月，天境生物将伊坦生长激素的商业化权益授权给济川药业。       安科生物、优诺金的长效生长激素处于2期临床，其中AK2017通过采用Fc融合蛋白结合技术延长半衰期，是重组人GH同源二聚体与通过突变的人IgG4-Fc的融合蛋白。       此外，除了皮下注射生长激素，儿童GHD患者还有望迎来口服疗法。2023年11月，Lumos Pharma生长激素促分泌素受体（GHSR）激动剂LUM-201治疗儿童GHD的两项2期研究（OraGrowtH210研究和OraGrowtH212研究）达到了所有主要终点及次要终点。       总结       生长激素药物的问世给儿童生长激素缺乏症（GHD）患者带来了希望。历经60多年的发展，生长激素药物的研发取得巨大成功，已从每日一次给药实现每周一次给药的跨越。全球儿童GHD的治疗规模也随之扩大，Frost & Sullivan数据显示其2030年有望达到60亿美元。目前，我国也已批准多款生长激素药物，但长效制剂相对国外较少，而且生长激素药物的市场渗透率也比较低。不过随着生长激素纳入集采，我国将有更多的儿童GHD患者接受生长激素治疗。期待未来有更多的新型生长激素药物获批上市，造福众多儿童GHD患者。       参考资料：       1.《生长激素行业深度：长效剂型快速放量，产品出海未来可期》.青山医药笔记.2024-02-07       2.《洞察o创新｜慎思而笃行：生长激素发展历程带来的挑战与风险》.全球健康产业创新观察.2023-07-20       3.《临床需求决定研发方向：生长激素的不断进步史》.医学界儿科频道.2022-10-14       【智药研习社近期直播预告】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

End of Phase 2 Meeting to Occur in Q2 2024, Initiation of LUM-201 Phase 3 Trial Expected in Q4 2024 Previously Announced Topline Data from Phase 2 OraGrowtH210 and OraGrowtH212 Trials of LUM-201 in Moderate PGHD Met All Primary and Secondary Endpoints Pisit “Duke” Pitukcheewanont, MD, Appointed Chief Medical Officer Conference Call Today at 4:30 PM EST AUSTIN, Texas, March 07, 2024 (GLOBE NEWSWIRE) -- Lumos Pharma, Inc. (NASDAQ:LUMO), a late-stage biopharmaceutical company advancing an oral therapeutic candidate for moderate Pediatric Growth Hormone Deficiency (PGHD), today announced financial results for the year ended December 31, 2023 and provided an update on clinical and regulatory activity. “The past year was a highly successful one for Lumos, culminating in the announcement of topline results from our Phase 2 OraGrowtH210 and OraGrowtH212 trials, which met all of their primary endpoints and provided substantial support for the advancement of LUM-201 toward a registrational Phase 3 trial in moderate PGHD,” said Rick Hawkins, Chairman and CEO of Lumos Pharma. “We expect to present full twelve-month and longer-term data in a subset of patients from these trials at a medical meeting in the second quarter of this year. Next steps for this program are also on track, with our End-of-Phase 2 Meeting with the FDA scheduled for next quarter, and preparation for our Phase 3 pivotal trial of LUM-201 well underway. We expect to be in position to initiate this registrational trial in the fourth quarter, pending positive feedback from the FDA. As evidenced by the Key Opinion Leader event we held last December, there is broad support among the pediatric endocrinology community for our novel approach to treating growth hormone disorders, and we remain confident in this asset’s potential to become the first oral therapeutic for the treatment of PGHD.” Upcoming Milestones Full 12-month data from OraGrowtH210 Trial to be presented in Q2 2024 at major medical meeting End of Phase 2 Meeting to occur in Q2 2024 Company expects to initiate Phase 3 pivotal trial of LUM-201 in Q4 2024 Recent Highlights Topline Data from Phase 2 OraGrowtH210 and OraGrowtH212 Trials of LUM-201 in PGHD Met All Primary and Secondary Endpoints OraGrowtH210 results showed LUM-201 dose of 1.6 mg/kg achieved annualized height velocities (AHV) of 8.2 cm/yr at 6 months and 8.0 cm/yr at 12 months, similar to growth rates for moderate PGHD population Delta at 6 and 12-month AHV between optimal LUM-201 dose of 1.6 mg/kg and rhGH comparator arm was within the non-inferiority margin (< 2 cm/yr) suggested by FDA for recent approvals Initial 24-month LUM-201 data from combined OraGrowtH210 and OraGrowtH212 Trials demonstrated a sustained AHV effect from Year 1 to Year 2 OraGrowtH212 demonstrated that, with only 20% of the GH concentration of injectable rhGH, LUM-201 achieved similar AHV, illustrating the greater efficiency of LUM-201’s unique pulsatile mechanism of action OraGrowtH210 Trial met pre-specified primary endpoint of validation of Predictive Enrichment Marker (PEM) test and secondary endpoint demonstrating 100% reproducibility of PEM-Positive classification No safety signal to date for LUM-201 Pisit “Duke” Pitukcheewanont, MD Appointed Chief Medical Officer Dr. Duke as he is known was promoted to the position of CMO effective January 1, 2024. In this role, Dr. Duke will provide his leadership in Lumos Pharma’s efforts to hone its clinical and regulatory strategy and will continue to oversee medical affairs as the Company prepares to initiate a pivotal Phase 3 trial evaluating oral LUM-201 as a therapeutic for moderate PGHD. Financial Results for the Year Ended December 31, 2023 Cash Position – Lumos Pharma ended the year on December 31, 2023, with cash, cash equivalents, and short-term investments totaling $36.1 million compared to $67.4 million on December 31, 2022. Cash on hand as of December 31, 2023, is expected to support operations through the third quarter of 2024. R&D Expenses – Research and development expenses were $22.1 million, an increase of $4.2 million for the year ended December 31, 2023, compared to the same period in 2022, primarily due to increases of $3.3 million in clinical trial expenses, $0.9 million in contract manufacturing expenses, $0.2 million in consulting expenses and $0.2 million in other expenses, partially offset by a $0.4 million decrease in personnel-related expenses. G&A Expenses – General and administrative expenses were $16.6 million, an increase of $0.9 million for the year ended December 31, 2023, compared to the same period in 2022, primarily due to increases of $0.5 million in personnel-related expenses, $0.4 million in royalty expenses and $0.1 million in travel expenses, partially offset by a $0.1 million decrease in other expenses. Net Loss – The net loss for the year ended December 31, 2023, was $34.0 million compared to a net loss of $31.1 million for the same period in 2022. Lumos Pharma ended Q4 2023 with 8,102,555 shares outstanding. Conference Call and Webcast Details The Company has scheduled a conference call and webcast for 4:30 p.m. ET today to discuss its financial results and to give an update on clinical programs. There will also be a question-and-answer session following management’s prepared remarks. Investors and the general public are invited to listen to the conference call. To access the call by phone, please click on this Registration Link, complete the form and you will be provided with dial-in details and a PIN. To avoid delays, we encourage participants to dial in to the conference call ten minutes ahead of the scheduled start time. The webcast may be accessed through this Webcast Link and may also be found in the “Investors & Media” section of the Lumos Pharma website, under “Events & Presentations.” A replay of the call will be available after the date of the call and may be accessed through the same link above or found on our website. About Lumos Pharma Lumos Pharma, Inc. is a clinical stage biopharmaceutical company focused on the development and commercialization of therapeutics for rare diseases. The Company was founded and is led by a management team with longstanding experience in rare disease drug development. Lumos Pharma’s lead therapeutic candidate, LUM-201, is a novel, oral growth hormone (GH) secretagogue, seeking to transform the ~$3.4B global GH market from injectable to oral therapy. LUM-201 is currently being evaluated in multiple Phase 2 clinical studies in Pediatric Growth Hormone Deficiency (PGHD) and has received Orphan Drug Designation in both the US and EU. For more information, please visit . Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements of Lumos Pharma, Inc. that involve substantial risks and uncertainties. All such statements contained in this press release are forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. A law that, in part, gives us the opportunity to share our outlook for the future without fear of litigation if it turns out our predictions were not correct. We are passionate about our business - including LUM-201 and the potential it may have to help patients in the clinic. This passion feeds our optimism that our efforts will be successful and bring about meaningful change for patients. Please keep in mind that actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make. We have attempted to identify forward-looking statements by using words such as “projected,” "upcoming," "will," “would,” "plan," “intend,” "anticipate," "approximate," "expect," “potential,” “imminent,” and similar references to future periods or the negative of these terms. Not all forward-looking statements contain these identifying words. Examples of forward-looking statements include, among others, statements we make regarding the advancement of oral LUM-201 to Phase 3, the expected timing of trial data presentations and FDA meetings, substantial support for the advancement of LUM-201 toward a registrational Phase 3 trial in moderate PGHD, that we expect to present full twelve-month and longer-term data in a subset of patients from these trials at a medical meeting in the second quarter of this year, that next steps for this program are on track, that we expect to be in position to initiate this registrational trial in the fourth quarter, that there is broad support among the pediatric endocrinology community for our novel approach to treating growth hormone disorders, that we remain confident in this asset’s potential to become the first oral therapeutic for the treatment of PGHD, that cash on hand as of December 31, 2023 is expected to support operations through the third quarter of 2024, and any other statements other than statements of historical fact. We wish we were able to predict the future with 100% accuracy, but that just is not possible. Our forward-looking statements are neither historical facts nor assurances of future performance. You should not rely on any of these forward-looking statements and, to help you make your own risk determinations, we have provided an extensive discussion of risks that could cause actual results to differ materially from our forward-looking statements including risks related to the continued analysis of data from our LUM-201 Trials, the timing and outcome of our future interactions with regulatory authorities including our end of Phase 2 meeting with the FDA, the timing and ability of Lumos to raise additional equity capital as needed to fund our Phase 3 Trial, our ability to project future cash utilization and reserves needed for contingent future liabilities and business operations, the ability to structure our Phase 3 trial in an effective and timely manner, the ability to successfully develop our product candidate, the effects of pandemics, other widespread health problems or military conflicts including the Ukraine-Russia conflict and the Middle East conflict and other risks could cause actual results to differ materially from those matters expressed in or implied by such forward-looking statements including information in the "Risk Factors" section and elsewhere in Lumos Pharma’s Annual Report on Form 10-K for the year ended December 31, 2022, as well as other reports filed with the SEC including our most recent Quarterly Report on Form 10-Q for the quarter ended September 30, 2023. All of these documents are available on our website. Before making any decisions concerning our stock, you should read and understand those documents. We anticipate that subsequent events and developments will cause our views to change. We may choose to update these forward-looking statements at some point in the future, however, we disclaim any obligation to do so. As a result, you should not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this press release. Investor & Media Contact: Lisa Miller Lumos Pharma Investor Relations 512-792-5454 ir@lumos-pharma.com Lumos Pharma, Inc. Consolidated Statements of Operations and Comprehensive Loss (unaudited) (In thousands, except share and per share amounts) Year Ended December 31, 2023 2022 Revenues: Royalty revenue $ 2,051 $ 1,523 Total revenues 2,051 1,523 Operating expenses: Research and development 22,096 17,857 General and administrative 16,569 15,706 Total operating expenses 38,665 33,563 Loss from operations (36,614 ) (32,040 ) Other income and expense: Other income, net 683 91 Interest income 1,868 874 Other income, net 2,551 965 Net loss before taxes (34,063 ) (31,075 ) Income tax benefit 29 13 Net loss $ (34,034 ) $ (31,062 ) Net loss per share of common stock Basic and diluted $ (4.18 ) $ (3.71 ) Weighted average number of common shares outstanding Basic and diluted 8,145,155 8,373,821 Other comprehensive income (loss): Unrealized loss on short-term investments 9 (9 ) Total comprehensive loss $ (34,025 ) $ (31,071 ) Lumos Pharma, Inc. Consolidated Balance Sheets (unaudited) (In thousands, except share and per share amounts) December 31, 2023 2022 Assets Current assets: Cash and cash equivalents $ 35,078 $ 56,007 Short-term investments 999 11,352 Prepaid expenses and other current assets 3,748 4,427 Other receivables 210 223 Total current assets 40,035 72,009 Non-current assets: Property and equipment, net — 53 Right-of-use asset 603 230 Total assets $ 40,638 $ 72,292 Liabilities and Stockholders' Equity Current liabilities: Accounts payable $ 890 $ 275 Accrued expenses 5,858 6,200 Current portion of lease liability 282 233 Total current liabilities 7,030 6,708 Long-term liabilities: Royalty obligation payable to Iowa Economic Development Authority 6,000 6,000 Lease liability 303 — Total liabilities 13,333 12,708 Commitments and contingencies: Stockholders' equity: Undesignated preferred stock, $0.01 par value: Authorized shares - 5,000,000 at December 31, 2023 and 2022; issued and outstanding shares - 0 at December 31, 2023 and 2022 — — Common stock, $0.01 par value: Authorized shares - 75,000,000 at December 31, 2023 and 2022; issued shares - 8,125,728 and 8,283,708 at December 31, 2023 and 2022, respectively, and outstanding shares - 8,102,555 and 8,267,968 at December 31, 2023 and 2022, respectively 81 82 Treasury stock, at cost, 23,173 and 15,740 shares held as of December 31, 2023 and 2022, respectively (196 ) (170 ) Additional paid-in capital 188,937 187,164 Accumulated deficit (161,517 ) (127,483 ) Accumulated other comprehensive loss — (9 ) Total stockholders' equity 27,305 59,584 Total liabilities and stockholders' equity $ 40,638 $ 72,292