Laboratorios Farmaceúticos Rovi SA

作者｜自由译员Isabelle 3月20日，生产巨头龙沙(Lonza)宣布与同为瑞士公司的罗氏（Roche）达成协议，将以12亿美元的价格从后者手中收购全球最大的生物制剂生产基地之一，罗氏位于加利福尼亚州瓦卡维尔（Vacaville）的工厂，以求在下一代药物的制造中取得绝对优势。 这家工厂1994年被基因泰克（Genentech）收购，2009年基因泰克成为罗氏子公司后，这家工厂一并归入了罗氏。该工厂利用转基因活细胞生产单克隆抗体，用来生产新一代药物。龙沙表示，瓦尔维尔工厂的生物反应器总容量目前约为33万升，在全球生物药生产基地之中数一数二。罗氏发言人指出，虽然生物药品的大规模生产对公司交付上市产品仍然很重要，但罗氏不再需要瓦卡维尔工厂的产能。该工厂目前生产托珠单抗（Actemra）、利妥昔单抗（MabThera/Rituxan）、奥美珠单抗（Ocrevus）、帕妥珠单抗（Perjeta）和帕托珠曲妥珠单抗注射液（Phesgo），擅长大规模生产生物制剂。但是，该工厂是罗氏最老的工厂之一，许多设备已经老化，一些创新工艺无法在此应用。随着罗氏的产品线越来越多元化，从单克隆抗体、双特异抗体到细胞疗法和个性化癌症疫苗，皆有涉及，罗氏需要的是更灵活的产能，以满足小批量个性化疫苗的生产需求。因此，去年5月31日，罗氏宣布决定剥离瓦卡维尔的基因泰克工厂，罗氏将之视为自身远大战略的一部分，旨在使产能能跟上未来产品线的需求。据媒体报道，如果找不到买家，瓦卡维尔工厂可能会在2029年关闭。最终，龙沙决定出手。罗氏制药技术运营全球主管 Susanne Hundsbaek-Pedersen 表示：“在与多家潜在战略合作伙伴进行尽职调查后，我们确信龙沙是最适合拥有瓦卡维尔基地的，能够继续为有需求的患者生产创新药物。”而龙沙方面则表示：“随着创新性的新疗法得到批准，预期整个CDMO行业对生物制剂产能的需求都会继续走高。在此情境下，收购瓦卡维尔工厂能使我们的客户立刻在美国这个全球最大的药品市场获得大量新产能。有了瓦卡维尔工厂，我们在西海岸也有了大规模生产能力，这家工厂与龙沙在东海岸朴茨茅斯现有的生物制剂基地以及在欧洲和亚洲的国际网络形成互补。”在满足惯例成交条件的前提下，该交易预计将于 2024 年下半年完成。收购完成后，瓦卡维尔工厂将并入龙沙生物制剂部门，该部门已在瑞士、新加坡、西班牙、美国和英国设有工厂。龙沙也已经开始规划该工厂的未来，计划在未来数年内再投资5亿瑞士法郎（5.61亿美元）扩建该工厂，以“满足市场对下一代生物制剂疗法的需求”。对于这家新工厂，龙沙寄予了厚望，提高了2024-2028年中期指导中对销售增长的预测。该公司预计，未来四年销量年复合增长率将为12%至15%，高于此前预期的11%至13%。 在龙沙去年10月公布的2024-2028中期指导中，销售增长预测为11-13%，现已更新。与此形成鲜明对比的是，今年1月，龙沙宣布关闭加利福尼亚州海沃德（Hayward）的哺乳动物临床生产工厂，裁员218人。发言人解释称：“作出这一决定的原因是CDMO市场需求集中在组合或整合临床和商业的产品上，而海沃德基地在临床范围以外提供的增长机会有限。”而就在那之前不久，去年10月初，龙沙宣布在位于瑞士施泰因（Stein）的基地新建一条商业灌装线，新增约115名雇员。  01  全球CDMO震荡调整几家欢喜几家愁?其实，龙沙强化制造能力，只不过是全球CDMO格局调整重组浪潮中的一朵浪花而已。今年2月，诺和控股拟斥资165亿美元收购康泰伦特（Catalent）。作为协议的一部分，康泰伦特的三个生产基地将以110亿美元的价格出售给诺和诺德，这将导致一些主要的外包制造工厂从公开市场上消失。对于这笔并购，礼来公司高层表示担忧。据华尔街日报透露，礼来首席财务官Anat Ashkenazi表示，康泰伦特是医药行业商业产品和管线产品制造不可或缺的部分，尤其在糖尿病和肥胖领域，礼来也有产品在康泰伦特工厂生产。鉴于礼来在糖尿病和肥胖治疗领域与诺和存在竞争关系，礼来首席执行官David Ricks也曾质疑此次合并对公司与康泰伦特的关系有何影响。另一方面，其他公司也正试图抓住这个机会，扩大自己的CDMO产品。最近， Laboratorios Farmacéuticos Rovi的首席执行官Juan López-Belmonte表示，诺和与康泰伦特的交易对这家西班牙公司来说，是未来几年赢得注射CDMO业务的“巨大机遇”。 从去年到今年，在全球范围内，CDMO行业关厂与开工共舞，裁员与扩建齐飞，可谓冷热不均、冰火两重天。3月19日，诺和诺德宣布，在中国天津投资约40亿人民币用于无菌制剂扩建项目，并举行了该扩建项目的奠基仪式。据悉，此次无菌制剂生产扩建项目将采用全球领先的隔离器技术，为制剂生产提供更高水平的无菌保障。3月19日，药明生物宣布其位于新加坡大士生物医药园的一体化CRDMO中心开工奠基，正式进入建设阶段。该中心占地13.5公顷，未来将提供生物药一体化研究、开发和生产服务。3月15日，诺华公司宣布，将斥资2.56亿美元扩建在新加坡的生物制药生产设施。该项目将在现场引入数字化和自动化，以提高制造业生产力，并帮助提高公司员工的技能。2月15日，CDMO 企业New Vision Pharmaceuticals宣布关闭位于美国佛罗里达州的无菌吹灌密封生产设施，88名员工失业。1月26日，龙沙宣布关闭广州工厂，裁员约300人。1月25日，新加坡迎来艾伯维2.23亿美元投资，扩建艾伯维在新加坡的小分子和生物制剂制造工厂，为该公司全球生产网络增加24,000升生物制剂原料药产能，并支持艾伯维现有产品以及新兴的免疫学和肿瘤学化合物。2023年10月，CDMO formulsolutions裁减了66名员工。2023年9月，韩国SK pharmteco以未公开的金额收购突破性药物中心（CBM）的控股权。细胞与基因治疗CDMO龙头Oxford Biomedica表示将以1500万欧元（1631万美元）的价格从法国的Institut Mérieux（梅里埃生物研究所）收购ABL Europe。这项交易将巩固Oxford Biomedica作为世界领先的细胞和基因治疗CDMO的地位。2023年8月，Emergent BioSolutions 宣布，将减少对旗下CDMO服务业务的投资，并不再强调该业务增长，同时公司将裁员400余人。2023年2月，赛默飞世尔在圣迭戈的三个生产基地裁员230人，主要从事制造业，工程师和科学家也被解雇；4月，关闭位于新泽西州普林斯顿的一家工厂，裁员113人，这家工厂主要负责生物制品开发和细胞治疗服务；5月，以Covid-19产品需求减少为由，在圣迭戈的三个工厂进行了第二轮裁员，共裁员218人；8月，宣布计划在佛罗里达州阿拉瓜的工厂裁员205人；11月，宣布关闭位于阿拉巴马州奥本市的工厂，并裁员97人。  02  国内CDMO企业如何卷中求进谋破局?3月26日晚间，国内最大的CDMO企业药明生物发布2023年年报。数据显示：公司营收170.34亿元，同比增长11.6%；公司拥有人应占纯利约34亿元，同比下降23.1%。这是药明生物上市以来，首次出现年度纯利下降。 近来，几位美国议员正在推进一项针对几家中国生物技术公司的法案草案，其中包括CRO和CDMO巨头药明康德和药明生物。该法案将禁止“与美国国家安全有关的外国对手生物技术公司”获得联邦合同或与寻求此类合同的公司合作。如果该法案通过，开发联邦老年医疗照顾保险（Medicare）和贫民医疗救济保险（Medicaid）计划中所含药物的公司将不得不选择其他外包商。药明康德和药明生物已经成为许多大大小小的生物制药公司的主要外包制造商和研发合作伙伴，包括礼来公司的Zepbound和Mounjaro。去年，药明康德65%的收入来自美国客户。前两周，Intron Health的分析师在一份报告中写道，药明康德的困境和诺和收购康泰伦特造成的潜在空白可能占到全球CDMO市场份额的20%左右。该团队表示，大部分开放份额将重新分配给其他西方CDMO企业。在3月27日药明生物的业绩发布会上，首席执行官陈智胜就近期的这些热点话题进行了回应：“没有和我们合作过的企业，可能会因为一些大环境的不确定性有所担忧。但是和我们合作过的企业，都非常了解我们的服务能力和质量。”药明生物表示，目前公司业务正常，将积极开拓海外市场，“跟随分子”项目进展顺利，数个潜在重磅项目正在顺利推进，将从2025年起贡献可观收入。公司将继续在德国、美国和新加坡扩建商业化生产产能。 行业第二的凯莱英于3月29日发布2023年年报，显示营业收入78.25亿元，比2022年的102.55亿下降不少，原因是失去了新冠大订单，但剔除大订单后同比增长24.37%。 凯莱英的基本盘是小分子药，核心技术是“连续反应技术”和“生物合成技术”，大分子生物制药也在布局，但尚未形成规模。年报还显示自由现金流23.08亿元，同比增长103.1%。这是之前凯莱英广受诟病的地方：前沿布局、扩张不够激进，现在反而成了优点，账上这一大堆现金正好应对医药寒冬。关于2024年的规划，凯莱英董事长洪浩曾在新年致辞中表示：“2024年是凯莱英全面加快国际化布局的一年，我们将在海外落地研发生产基地。”近日，博腾制药位于上海浦东外高桥的抗体和抗体偶联药物（ADC） GMP中试生产线建成并投入使用，标志着博腾正式具备为全球生物药和研发机构提供抗体和ADC从临床前候选化合物（PCC）到新药临床试验申请（IND）及GMP生产的一站式CDMO服务能力。今年1月，博腾在重庆投资10.85亿打造ADC商业化平台，建成后，将达到年产大分子抗体原液28,800kg，ADC偶联原液46,080kg，大分子抗体制剂成品270万瓶，ADC偶联制剂成品220万瓶的生产能力。但是，在博腾制药发布的年度业绩预告中，2023年总营收预计为35.17至38.69亿元，同比下降45%至50%，主要原因系公司前期收到的重大订单去年同期交付较多所致——2021年11月和2022年2月，博腾股份先后接到来自辉瑞的两个CDMO订单，采购订单金额分别为2.17亿美元和6.81亿美元。  写在最后  疫情期间，CDMO企业享受到了诸多红利，疫情退去，需求减少、产能过剩、竞争加剧、不确定的国际关系，皆化为阵阵寒风。无论国内国外，CDMO企业都在求变突围。机会与挑战共存，希望与困难同在，大浪淘沙，是强者恒强，还是后来居上，我们不妨拭目以待。 主要参考文献 Fierce Pharma: Lonza strikes $1.2B deal to buy mammoth Roche plant amid CDMO industry upheavalRoche Media Statement: Roche To Divest Legacy Genentech Facility in Vacaville, California, asPart of Long-term Strategy to Evolve Manufacturing CapabilitiesRoche Media Statement: Roche enters into a definitive agreement with Lonza, which willacquire the Genentech manufacturing facility in Vacaville, California,USALonza News Release: Lonza Signs Agreement to Acquire Large-Scale Biologics Site in Vacaville (US) from RocheLonza News Release: Lonza Delivers Solid 2023 Performance with 10.9% CER Sales Growth and 29.8% CORE EBITDA MarginPharmaVoice: 3 questions hanging over the Novo-Catalent dealSeeking Alpha: Lonza: The Day Has Come, And We Lower Our Expectation医药经济报公众号：《龙沙12亿美元收购罗氏美国工厂，药明、诺和诺德等供应链新布局，全球制药产能加速重构？》雪球chuminhua药融圈微博：《1600万美元！CGT CDMO领域又一起并购》证券日报之声公众号：《全球生物技术融资回暖 药明生物能否走出“至暗时刻”》熠恒庭院公众号：《由《生物安全法案》再谈凯莱英的风险》凯莱英Asymchem公众号：《初心如磐，驰而不息！凯莱英董事长洪浩博士2024新年致辞》凯莱英Asymchem公众号：《【重磅】技术赋能 向阳而行：凯莱英医药集团2023年度业绩报告》自贸壹号SimbayPark公众号：《里程碑！博腾股份抗体和ADC GMP中试生产线建成投用》原料药情报局公众号：《投资10.85亿！重庆博腾打造ADC（抗体偶联药物）商业化平台》药明生物公众号：《药明生物2023年业绩稳健增长》共建Biomedical创新生态圈！如何加入BiG会员？

Lonza's move comes amid several seismic shifts in the CDMO market. In a bid to corner contracts on next-generation medicines, production juggernaut Lonza is picking up one of the world’s biggest biologics manufacturing facilities from its Swiss compatriot Roche. Lonza is laying out $1.2 billion in cash to acquire Genentech’s factory in Vacaville, California, where it already has plans to plug in another 500 million Swiss francs ($561 million) to expand the plant in the coming years, the CDMO said Wednesday. The deal will help Lonza bulk up large-scale biologics manufacturing capacity for both commercial-scale mammalian contract manufacturing and clinical-stage projects, the company explained in a press release. The Vacaville facility boasts bioreactor capacity of around 330,000 liters, making it one of the world’s biggest biologics manufacturing sites by volume, Lonza said. As part of the acquisition, Lonza will extend job offers to around 750 Genentech staffers currently employed at Vacaville. Lonza is already looking to the plant’s future, too. The company plans an expansion project worth around 500 million francs to help “satisfy demand for the next generation of mammalian biologics therapies.” The CDMO will take over the supply of the products currently manufactured in Vacaville by Roche. Lonza will provide committed volumes over the medium term before phasing out the Roche products as the site transitions to serve the CDMO’s customers. Lonza and Roche expect the deal for the facility to close in the second half of 2024. Once the acquisition is complete, the Vacaville site will join Lonza’s Biologics division, which operates manufacturing facilities in Switzerland, Singapore, Spain, the United States and the United Kingdom. Lonza has high hopes for the new facility and is upgrading its mid-term guidance from 2024 through 2028 in turn. The manufacturer now expects sales to grow 12% to 15% over the four-year stretch, up from a previous window of 11% to 13%.  Lonza is beefing up its manufacturing capacity as the global CDMO landscape faces seismic changes. Novo Holdings’ proposed $16.5 billion acquisition of Catalent—and the related $11 billion sale of three manufacturing sites to Novo Nordisk—is set to take some major contract manufacturing space off the open market. Eli Lilly CEO David Ricks has questioned the implications of the merger on his company’s relationship with Catalent given Lilly’s competition with Novo in diabetes and obesity treatments. Other companies are trying to seize the opportunity to expand their own CDMO offerings. Juan López-Belmonte, CEO of Laboratorios Farmacéuticos Rovi, recently described the Novo-Catalent deal a “tremendous opportunity” for the Spanish company to win over injectable CDMO business in the years ahead. Meanwhile, several U.S. lawmakers are advancing a draft bill targeting several Chinese biotech companies, including the CRO and CDMO giants WuXi AppTec and WuXi Biologics. The bill would forbid “foreign adversary biotech companies of U.S. national security concern” from getting federal contracts or working with companies that seek such contracts. If enacted, companies that develop drugs offered under the federal Medicare and Medicaid programs would have to choose other contractors. The two WuXi firms have become major contract manufacturers and R&D partners for many biopharma companies large and small, including Lilly for its Zepbound and Mounjaro. Last year, WuXi AppTec generated 65% of its revenue from its customers in the U.S. The potential void created by WuXi’s woes and the Novo-Catalent buyout could represent about 20% of global CDMO market share, analysts at Intron Health wrote in a note Tuesday. The team suggests the majority of the open share will be redistributed to other Western CDMOs, and Lonza, as an established CDMO player, is “well placed to benefit," the Intron team said.

The COVID vaccine manufacturing relationship between Rovi and Moderna is built on a 10-year partnership formed in 2022. As part of a long-term partnership between Spain’s Laboratorios Farmacéuticos Rovi and Moderna, the former company is bringing a new plant into the mix for production of COVID-19 vaccines bound for the U.S. market. During an inspection in January, FDA staffers were satisfied with Rovi’s active substance manufacturing plant in Granada, Spain, effectively allowing Spikevax doses made at the facility to be sold in the U.S., Rovi CEO Juan López-Belmonte said on a Tuesday call with investors. The FDA’s clearance of Rovi’s drug substance plant comes after the agency in September approved the company’s three injectable plants in or near Madrid to perform fill-finish syringe manufacturing of Spikevax, according to the CEO. The manufacturing relationship between Rovi and Moderna is built on a 10-year partnership the two firms formed in 2022. At that time, Moderna promised to invest in Rovi’s Madrid facility to boost capacity there. Last year, Rovi's CDMO business grew revenue 1% to 409 million euros, while the entire company’s revenue also increased by 1% to about 830 million euros. Rovi’s CDMO services unit could grow further in the years ahead thanks to Novo Nordisk’s proposed acquisition of the CDMO giant Catalent, López-Belmonte said. Calling the deal a “tremendous opportunity,” the Rovi CEO noted that a significant player in the injectable CDMO business is likely going to be exiting the game. Considering the timeline of contract manufacturing agreements, López-Belmonte said Rovi isn’t sure whether it’ll attract new customers this year because of the Catalent buyout. But the company does anticipate additional customers and volumes over the next few years, he said. On the specialty medicines side of Rovi’s business, the company is hoping to turn a page on some manufacturing shortfalls and win a much-delayed FDA nod for Risvan, an intramuscular formulation of Johnson & Johnson’s antipsychotic drug Risperdal. Rovi got its first complete response letter from the FDA, citing shortfalls in the application package, in September 2021. Then about a year later, the FDA issued a second rejection, and this time, manufacturing was cited as an additional problem. Back then, the agency flagged issues at a third-party supplier and highlighted observations noted during a pre-approval inspection of Rovi’s Madrid plant. In July 2023, the FDA sent out another complete response letter, citing the pending resolution of manufacturing deficiencies. Rovi responded to four observations in September, and the FDA has set a new target decision date of March 29. The company is currently looking for a commercialization partner for Risvan in the U.S. Without a contribution from the U.S., the drug, known as Okedi in Europe, generated 14.4 million euros in sales in its second year on the European market, compared with 2.2 million euros in 2022. López-Belmonte described Okedi’s launch as above the company’s expectations, noting that the company has rolled out a salesforce across Europe. The CEO expects the current monthly injection to reach its level of peak sales in the next three to four years. By that time, the company hopes to have developed an even longer-acting version that can be given once every three months. Risvan/Okedi is the first product based on Rovi’s long-acting drug delivery technology, called ISM. The company is trying to apply the technology to developing an extended-release version of Novartis’ popular aromatase inhibitor Femara, although clinical development of an annual dosing regimen is currently on hold; a three-monthly formulation is moving into phase 1. Besides Okedi, the heart medicine Neparvis and the cholesterol-lowing combo Orvatez each helped Rovi’s specialty pharma business, posting gains of 16% and 8% respectively in 2023. For 2024, Rovi expects revenues to decline by mid-single-digit percentages. But the company also hopes factors such as a possible FDA approval of Risvan, higher demand for COVID vaccines and CDMO services growth will lift its performance.