A Single-Arm, Open-Label, Phase I Study to Determine the Safety, Tolerability and Preliminary Efficacy of Obecabtagene Autoleucel in Patients With Severe, Refractory Systemic Lupus Erythematosus

This is a Phase I study of obecabtagene autoleucel (obe-cel), autologous T cells engineered with a chimeric antigen receptor (CAR) targeting CD19, to establish the tolerability, safety, preliminary efficacy, and pharmacokinetics of obe-cel in patients with severe, refractory SLE.

开始日期2024-02-02

申办/合作机构

Autolus Ltd.

NCT06173518 / Recruiting临床1期

A Single-Arm, Open-Label, Multi-Centre, Phase Ib Study Evaluating the Safety and Preliminary Efficacy of AUTO1 in Pediatric Patients With CD19-Positive Relapsed/ Refractory (r/r) B Cell Acute Lymphoblastic Leukemia (B ALL) and Aggressive Mature B Cell Non-Hodgkin Lymphoma (B NHL)

This is a Phase Ib study to evaluate the safety and efficacy of autologous T cells engineered with a chimeric antigen receptor (CAR) targeting CD19 in pediatric patients with relapsed or refractory (r/r) B cell acute lymphoblastic leukemia (B ALL) and r/r B cell Non-Hodgkin lymphoma (B NHL)

开始日期2023-11-16

申办/合作机构

Autolus Ltd.

ACTRN12621000762853 / Recruiting临床1期

Phase I Clinical Trial of MB.CART19.1 CD19 Chimeric Antigen Receptor (CAR)T Cells in Relapsed or Refractory CD19-Positive Haematological Malignancy

开始日期2021-07-21

申办/合作机构

Metro North Hospital & Health Service

100 项与 Obecabatagene autoleucel 相关的临床结果

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100 项与 Obecabatagene autoleucel 相关的转化医学

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100 项与 Obecabatagene autoleucel 相关的专利（医药）

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项与 Obecabatagene autoleucel 相关的文献（医药）

2024-12-01·Current Research in Translational Medicine

Point of care CD19 chimeric antigen receptor (CAR) T-cells for relapsed/refractory acute myeloid leukemia (AML) with aberrant CD19 antigen expression

Article

作者: Jacoby, Elad ; Shem-Tov, Noga ; Itzhaki, Orit ; Shouval, Roni ; Avigdor, Abraham ; Danylesko, Ivetta ; Yerushalmi, Ronit ; Toren, Amos ; Nagler, Arnon ; Shimoni, Avichai

Relapsed/refractory (r/r) acute myeloid leukemia (AML) is associated with poor prognosis. CD19 is a B-cell marker, is aberrantly expressed in AML, mostly with t(8; 21)(q22; q22.1). Here we report the results of a phase 2 study giving point of care produced CD19 CAR T- cells for r/r AML with aberrant expression of CD19 (NCT04257175). Lymphodepletion included fludarabine and cyclophosphamide The response was evaluated by bone marrow (BM) aspiration on day 28. Six patients (5 adults and 1 child) were included. Median number of previous chemotherapy lines was 4 (range, 3-8) and four patients received CAR T-cells 8-18 months post allogeneic hematopoietic stem cell transplantation (allo-HSCT). Cytokine release syndrome (CRS) of any grade occurred in all patients, and 1 patient had grade 3 CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 2 patients at low grades. Tocilizumab was administered to 2 patients and corticosteroids to 3 patients. Four patients achieved a complete remission (CR), while 2/6 progressed (PD). Three patients (2 with CR and 1 with PD) underwent allo-HSCT (it was the second transplant in 2) 2-5 months post CAR T-cells infusion. The median duration of response in patients achieving CR was 8.5 (range; 3-14) months. However, all patients eventually died within 5 (1-18) months. In conclusion, CD19 CAR T- cell treatment for AML is feasible and safe. However, the response is short and should be followed by allo-HSCT. Hopefully, future long term results will be improved by combining the CAR T- cell therapy with the emerging novel effective anti-leukemic compounds.

2024-09-01·MedComm

Targeting chronic lymphocytic leukemia with B‐cell activating factor receptor CAR T cells

Article

作者: Luo, Yan ; Li, Shuhua ; Qie, Yaqing ; Murthy, Hemant S. ; Gadd, Martha E. ; Qin, Hong ; Rivera‐Valentin, Rocio ; Yassine, Farah ; Liu, Andrew ; Dronca, Roxana ; To, Tommy ; Shao, Qing ; Kharfan‐Dabaja, Mohamed A.

AbstractThe challenge of disease relapsed/refractory (R/R) remains a therapeutic hurdle in chimeric antigen receptor (CAR) T‐cell therapy, especially for hematological diseases, with chronic lymphocytic leukemia (CLL) being particularly resistant to CD19 CAR T cells. Currently, there is no approved CAR T‐cell therapy for CLL patients. In this study, we aimed to address this unmet medical need by choosing the B‐cell activating factor receptor (BAFF‐R) as a promising target for CAR design against CLL. BAFF‐R is essential for B‐cell survival and is consistently expressed on CLL tumors. Our research discovered that BAFF‐R CAR T‐cell therapy exerted the cytotoxic effects on both CLL cell lines and primary B cells derived from CLL patients. In addition, the CAR T cells exhibited cytotoxicity against CD19‐knockout CLL cells that are resistant to CD19 CAR T therapy. Furthermore, we were able to generate BAFF‐R CAR T cells from small blood samples collected from CLL patients and then demonstrated the cytotoxic effects of these patient‐derived CAR T cells against autologous tumor cells. Given these promising results, BAFF‐R CAR T‐cell therapy has the potential to meet the long‐standing need for an effective treatment on CLL patients.

2024-08-23·Leukemia & Lymphoma

Advances in the treatment of adults with newly diagnosed B-cell acute lymphoblastic leukemia: the role of frontline immunotherapy-based regimens

Review

作者: Kantarjian, Hagop ; Jabbour, Elias ; Short, Nicholas J.

Blinatumomab and inotuzumab ozogamicin (INO) are both active in relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) and improve outcomes compared with conventional chemotherapy in this setting. Several prospective clinical trials have explored the use of these agents in adults with newly diagnosed B-cell ALL, with promising outcomes observed in younger and older adults and in both Philadelphia chromosome (Ph)-positive and Ph-negative ALL. These novel regimens result in high rates of deep measurable residual disease (MRD) negativity and may improve survival compared with chemotherapy-only approaches, allowing for less reliance on intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). This review discusses novel approaches to integrating INO and/or blinatumomab into frontline ALL regimens, including the potential role of chemotherapy-free regimens in some subgroups. The role of MRD monitoring is also discussed, including how this can inform decisions for consolidative allogeneic HSCT or investigational approaches with CD19 CAR T-cells.

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项与 Obecabatagene autoleucel 相关的新闻（医药）

2024-10-03

·BioSpace

Meeting on the Mesa to Highlight Cell and Gene Therapy Opportunities, Challenges

Phoenix, Arizona/ iStock, Sean Pavone Stephen Majors from the Alliance for Regenerative Medicine, which hosts the conference, spoke with BioSpace about what the more than 2,000 attendees can expect to learn next week in Phoenix about the pressing issues confronting the industry. The 2024 Cell & Gene Meeting on the Mesa has a new location this year—held Oct. 7–9 in Phoenix, having moved from Carlsbad, Calif. Despite the change in venue, the industry continues to face the same regulatory, manufacturing and commercialization challenges as the sector hits an inflection point. BioSpace will provide on-site coverage of the three-day event, where more than 2,000 attendees will get an update from key stakeholders on the industry’s progress and the stumbling blocks that are impeding the advancement of cell and gene therapies (CGTs). One of the biggest business challenges for the sector is the investment headwinds that have continued this year, according to the Alliance for Regenerative Medicine (ARM), the Washington, DC–based advocacy organization that represents the industry and hosts the annual Meeting on the Mesa. Stephen Majors, global head of communications at ARM, told BioSpace that capital markets “have been really tough” the past few years for CGT. “There’s a lot of companies in the space pursuing a smaller amount of money,” he observed. “Inflation projections were, of course, a driver of this because the gene therapy companies tend to be the furthest away from commercialization and therefore inflation concerns hit them hardest,” Majors said. “We’re hopeful that with the reduction of interest rates and a better inflation outlook going forward, we’ll start to see more money flow into the sector.” Manufacturing, Commercialization Hurdles Majors said that manufacturing is also a major challenge for the industry due to a lack of standardization and the fact that scale-up has often been an obstacle to regulatory approval and commercialization. “There are still some manufacturing challenges and the ability to produce these therapies at scale at the demand that they’re needed. That’s something that the sector’s still working through,” according to Majors. A Government Accountability Office report last year found that while regenerative medicine technologies—including gene therapies, cell therapies and tissue-engineered products—are highly promising, they are being held back by the lack of widely accepted standards and guidelines to govern their use, development and manufacture. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research (CBER), provided a sobering assessment in May at the 2024 American Society of Gene & Cell Therapy conference about the opportunities and challenges facing the CGT industry. He said that while it’s “an exciting time” for gene therapies in particular—including the approval of competing therapies for sickle cell disease —there are “some real challenges” including manufacturing, clinical development timelines and different global regulatory requirements . After their groundbreaking approvals in late 2023, infusions of Vertex-CRISPR Therapeutics’ and bluebird bio’s sickle cell gene therapies have recently begun, offering hope to patients and the companies, which are looking to jumpstart revenues. “Those of us who have been watching this for a while were always expecting these launches to be kind of slow with steady uptick over time, because of the length of time involved in the identification of eligible patients and in the consultation process they have with their doctors about whether this is the right therapy for them,” Majors said. A panel session at Meeting on the Mesa on commercializing cell and gene therapies in today’s “dynamic market” environment will be a “hot” session given other recent product launches, according to Majors. He expects “some lessons learned from that, maybe some wisdom and advice for launches yet to come.” For the second year at the conference, ARM CEO Tim Hunt will lead a session on the importance of ethics in cell and gene therapies. Majors said it is meant to be a broad-based look at several issues, including “the pricing and value” of CGT, global access such as “how long it will be” before therapies reach patients in developing and low- and middle-income countries, and ultra-rare diseases in which the sizes of patient populations “fall outside what usually works from a commercialization perspective.” According to market research and consulting firm Nova One Advisor, the global CGT market was valued at more than $18.1 billion in 2023 and is expected to reach approximately $97.3 billion by 2033. While CGT developers face challenges along several key stages of the product life cycle, the firm notes that “key success factors such as enabling patient access, managing supply chain and manufacturing operations, evidencing compliance with increasingly complex regulatory requirements and alternate business models impose a greater burden” for CGTs than for chemical-based pharmaceuticals. Regulatory Environment Takes Center Stage On the regulatory front at Meeting on the Mesa, the conference will hear from Nicole Verdun, director of the FDA’s Office of Therapeutic Products within CBER. According to Majors, Verdun will “give us an update on where the FDA is in terms of how they’re looking at cell and gene therapies, their staffing levels to ramp up with the submissions,” as well as accelerated approvals and “other details about the regulatory frameworks they’re looking at” for CGT. Scott Gottlieb, former FDA commissioner, will participate in a fireside chat at the conference. In 2019, as the head of the agency, Gottlieb predicted that the regulator would be approving 10 to 20 cell and gene therapy products annually by 2025. Early next year, his book The Miracle Century: Making Sense of the Cell Therapy Revolution is slated to be published. In it, he “tackles the issues that must be addressed to enable wide adoption of these treatments,” according to the publisher’s description . Majors said that Gottlieb will provide Meeting on the Mesa with an overview of “where we are in the field right now” and “what we can expect over the next few years.” “Historically, we haven’t seen much of a difference between the U.S. and Europe in approvals,” according to Majors. “There were a handful of gene therapies that got approved in Europe first before they got approved here. But what we’re seeing more recently is the U.S. starting to have more approvals.” ARM in its annual Cell & Gene State of the Industry Briefing in January predicted that the sector could see up to 17 regulatory approvals in the U.S. and European Union this year. However, Majors in an update to BioSpace said the organization has cut its forecast a bit and is now predicting up to 14 approvals, with eight in the U.S.—including the FDA’s first approval in March for an autologous gene therapy from Orchard Therapeutics to treat the rare metabolic disease metachromatic leukodystrophy in children, and the FDA nod in April for Pfizer’s hemophilia B gene therapy Beqvez. “If we looked at last year as kind of the breakthrough year of gene therapy, which it certainly was, this year we’re seeing a lot of advances in cell therapy,” Majors said. “There’s been a number of really impressive fundraises from cell therapy companies. There’s been a lot of excitement and progress in autoimmune diseases. And there’s been expansion of CAR T therapies into earlier lines of treatment.” In February, the FDA granted approval to Iovance Biotherapeutics’ li as the first one-time cell therapy for a solid tumor and the first tumor-infiltrating lymphocytes therapy. In April, the regulator greenlit two CAR T cell therapies for the earlier treatment of multiple myeloma —BMS and 2seventy Bio’s Abecma, and J&J and Legend Biotech’s Carvykti. And in August, Adaptimmune Therapeutics’ Tecelra became the first FDA-approved engineered cell therapy for solid tumors and the first new synovial sarcoma therapy in more than a decade. Majors sees Autolus Therapeutics’ FDA application for its next-generation CAR T therapy obe-cel in relapsed/refractory adult acute lymphoblastic leukemia as an important milestone, with a PDUFA target action date of Nov. 16. According to Autolus, obe-cel is a CD19 CAR T cell investigational therapy designed to overcome the limitations in clinical activity and safety compared to current CD19 CAR T cell therapies. The FDA in January pushed for a class-wide boxed warning on all commercial BCMA- and CD19-directed CAR T cell immunotherapies due to the “risk of T cell malignancies, with serious outcomes, including hospitalization and death.” “There was correlation but there wasn’t necessarily causation,” Majors said about the regulator’s findings on CAR T therapies and secondary cancers, noting that “the benefits of these therapies continue to outweigh the risks” providing an “important tool at the disposal of physicians for patients with serious, aggressive forms of cancer.”

免疫疗法细胞疗法上市批准基因疗法

2024-09-20

·EndPoints

Lexicon's president to step down as decision date looms; Sarepta welcomes Lilly, GSK vet to board

→ The top leadership at Lexicon Pharmaceuticals is still undergoing a major makeover as president and COO Jeff Wade heads for the exit on Sept. 30 after 25 years with the Texas-based biotech. Wade won’t be around for the outcome of Lexicon’s latest attempt at an FDA nod in type 1 diabetes for sotagliflozin , which has a Dec. 20 decision date. The drug has already been approved for heart failure and is marketed as Inpefa . Lexicon laid off about 75 people in its sales and commercial teams in August “to right-size our promotional efforts around Inpefa for heart failure and reallocate resources to prepare for our potential launch” in type 1 diabetes and chronic kidney disease, CEO Mike Exton said in a statement. Exton succeeded Lonnel Coats as CEO a month earlier. → Sarepta Therapeutics has appointed Genmab chair Deirdre Connelly to the board of directors. Connelly had a 26-year career with Eli Lilly before pivoting to GSK in 2009 as president, North America pharmaceuticals until her retirement in 2015. She’s also a board member at Macy’s and Lincoln Financial Group . Like Janet Woodcock before him, CBER Director Peter Marks helped Sarepta cross the goal line with a label expansion in June for its Duchenne muscular dystrophy treatment Elevidys — overruling his own staff and befuddling experts. → Mitchell Chan has replaced Vit Vasista as CFO of Regenxbio at a time when the company plans to start a pivotal study for its own Duchenne gene therapy. It’s another big change for Regenxbio after Ken Mills became executive chairman and Curran Simpson succeeded Mills as CEO on July 1. Chan spent a year with Catalio Capital Management as operating partner after he was elevated to the CFO post at Viela Bio. Vasista had been finance chief since 2009 and will be an advisor until Jan. 3. → Here’s a look at some CEO news that we covered earlier this week: Former Kite Pharma commercial chief Warner Biddle has succeeded Peter Maag as CEO of Kyverna Therapeutics , which also added ex-Kite CEO Christi Shaw to the board. Shares $KYTX of Kyverna have taken a precipitous fall since its $319 million IPO in February. Ochre Bio co-founder Jack O’Meara is calling it quits after five years as CEO, but he tells Lei Lei Wu that he has an Alzheimer’s startup in the works. In a LinkedIn post announcing his departure, O’Meara also said that former F-star CEO and current Levicept chief Eliot Forster will be interim executive chair. And Shilpa Sambashivan has been promoted to CEO of Nura Bio , which stapled an additional $68 million to its Series A — bringing its total to $141 million. Sambashivan was a project team lead at Amgen before becoming a founding member at Nura Bio. → Matt Kane is taking the top spot at Celyad Oncology , a Belgian biotech that has seen considerable turnover at the top. Celyad co-founder Michel Lussier filled in as interim CEO for a second time after Georges Rawadi ’s sudden exit last December; he also took over when Filippo Petti stepped down in 2022. Kane co-founded Precision BioSciences with Derek Jantz and Jeff Smith , leading the company until he joined epigenome editing startup Tune Therapeutics as CEO in 2021. Kane’s LinkedIn page indicates that he left Tune in April, a year after he hired Jantz as CSO. → Ex- Prometheus Biosciences chief Mark McKenna has found a CFO at his new I&I bet, Mirador Therapeutics . Gregg Gilbert had been a managing director in the healthcare investment banking group for Bank of America Securities since 2021 and worked at Bank of America Merrill Lynch for 15 years. After selling Prometheus and its inflammatory bowel disease drug to Merck for $10.8 billion , McKenna wasted little time getting Mirador off the ground with a $400 million Series A in March, one of the largest private financing rounds of 2024. → GLP-1 competitor Structure Therapeutics has promoted Blai Coll to CMO and welcomed Ashley Hall as chief development officer. Coll, who replaces Mark Boch , had led clinical development for Raymond Stevens ’ crew since May 2022 and was cardiovascular and metabolic platform lead, medical affairs at the end of a six-year stint with Amgen. Hall is an Amgen vet in her own right who held the role of development chief at Reneo Pharmaceuticals . Structure’s stock price soared in June $GPCR when it produced efficacy data with its oral GLP-1 GSBR-1290 that was on par with Eli Lilly’s obesity drug orforglipron . → Novartis and Gilead veteran Matthias Will has succeeded Edgar Braendle as chief development officer at Autolus Therapeutics . Will had led clinical development at CRISPR Therapeutics and CytomX before his most recent gig as CMO of Dren Bio . The FDA is expected to make a decision by Nov. 16 on Autolus’ CD19-directed CAR-T obecabtagene autoleucel , or obe-cel . → According to an SEC filing , Crinetics chief commercial officer Jim Hassard will pack his bags on Oct. 14 in what’s described as a “termination without cause.” The 17-year Amgen vet came to Crinetics from Arrowhead Pharmaceuticals in March 2022. Phase 3 successes with its acromegaly drug paltusotine have propelled Crinetics to an NDA filing “later this year” and “an expected market launch in 2025,” CEO Scott Struthers said in the San Diego biotech’s second-quarter report. CFO Mark Wilson cited personal reasons for his own upcoming departure, which was also included in Crinetics’ Q2 update. → Allosteric drug discovery shop HotSpot Therapeutics has introduced Alison O’Neill as CMO. O’Neill is the former medical chief at Surface Oncology , which was acquired by Coherus BioSciences last year for $65 million. She had a senior leadership role in the global oncology division at Sanofi and was VP of clinical development for Radius Health . → Ex- Icosavax CEO Adam Simpson has landed at Frazier Life Sciences as a venture partner on its company creation team and will work out of Frazier’s office in San Diego. Simpson sold the vaccine developer to AstraZeneca last December, and his previous company — celiac disease specialist PvP Biologics — was purchased by Takeda in 2020. → Ruben Tommasi has been named CSO of Entact Bio , a Watertown, MA-based biotech led by ex- Ribon Therapeutics CEO Victoria Richon that is developing enhancement-targeting chimeric molecules, or ENTACs. Tommasi has also held this role at Dunad Therapeutics and AstraZeneca spinout Entasis Therapeutics . Entact Bio has kept a relatively low profile since its $81 million Series A in 2022, but it did show up in Peer Review this spring when it recruited fellow Entasis vet Michael Gutch as COO. → Third Rock ’s Treg developer Abata Therapeutics has resurfaced in Peer Review for the first time in more than a year, naming Joanne Beck as chief technical officer. The Shire and Celgene alum is the ex-technical chief at Aerium Therapeutics , the Covid biotech led by Rajeev Venkayya that recently shut down because of a surge in new variants. In April 2023, Abata poached Sonoma Biotherapeutics CMO Leonard Dragone for the same role . → Led by ex- Teva R&D chief Michael Hayden , neuro biotech Prilenia has tapped Rob Lauzen as CFO and Jason Marks as chief legal officer. Lauzen was VP, investor relations and head of financial planning & analysis at Dyne Therapeutics , which made a CMO change and lost its COO and CBO earlier this month. Marks just had a short stint with Teva as a senior legal advisor to global transactions and global finance. The Bausch Health alum has also been chief legal and compliance officer at Amarin . → San Francisco eye disease biotech Ray Therapeutics has selected Christopher Whitmore as CFO. Whitmore had held the same position with Immune-Onc Therapeutics since July 2022, and he was VP, finance & administration for Harpoon Therapeutics from 2018-21. Ray Therapeutics, which hauled in a $100 million Series A last year, will test its gene therapy RTx-015 in patients with retinitis pigmentosa. → Tris Pharma has promoted VP of marketing Manesh Naidu to the role of chief commercial officer. Naidu joined the New Jersey-based company in 2023 after a stint as chief marketing officer of Althera Pharmaceutical . Naidu’s résumé also includes stints at McKinsey , Mallinckrodt , Novartis, Pfizer and Bellerophon Therapeutics . In May, Tris snagged the first liquid non-stimulant ADHD drug approval in the US. Onyda XR will be used to treat ADHD in children at least 6 years of age. → Backed by Jeff Bezos , Seattle-based Nautilus Biotechnology has named Kentaro Suzuki as chief marketing officer. Suzuki most recently served as VP and general manager of Agilent Technologies’ mass spectrometry division. Before that, he was with Takeda and Hewlett-Packard . → San Francisco-based 89bio has appointed Teresa Perney as chief regulatory and quality officer. Perney held this title at EQRx after five years with Myovant Sciences as SVP of regulatory and quality. Madrigal Pharmaceuticals finally broke through with an FDA approval for metabolic dysfunction-associated steatohepatitis (also referred to as NASH), and 89bio is enrolling patients for late-stage studies of pegozafermin — one for non-cirrhotic MASH and another for MASH with compensated cirrhosis. “I’m eager to leverage my experience to navigate the regulatory landscape and help bring this innovative therapy to patients worldwide,” Perney said in a statement . → There’s also a new regulatory chief at Disc Medicine : Steve Caffé spent five years with CRISPR Therapeutics as head of regulatory affairs until his departure last December. Earlier, he had numerous stops as a regulatory exec with such companies as Ra Pharmaceuticals , Sucampo Pharmaceuticals , AMAG Pharmaceuticals and MedImmune . Shares of Disc $IRON fell sharply in early April after mixed data with its drug for a rare blood disorder called erythropoietic protoporphyria, but have rebounded since. → Although AI-designed drugs haven’t exactly lived up to the hype, companies like BPGbio are trying to flip the narrative. This week, GSK alum John Beeler has joined the team as SVP of business development. Beeler comes to BPGbio from Bristol Myers Squibb , where he took on the role of business development search & evaluation lead. → Macrocycle startup Circle Pharma has brought in Marie Evangelista as SVP and head of cancer biology, and promoted Constantine Kreatsoulas to SVP and head of discovery technology sciences. Evangelista spent the last two years as VP of oncology at one of the most ambitious AI drug developers , Recursion . The longtime Genentech vet also had a brief tenure with Frontier Medicines as senior director of translation medicine. Kreatsoulas had a nine-year run at GSK and was the pharma giant’s interim head, computational toxicology before coming to Circle in 2021 as head of research and VP, research informatics and computational chemistry. Circle disclosed its $54 million Series D in an SEC filing this summer. → South San Francisco-based Ideaya Biosciences has recruited Douglas Snyder as general counsel. Snyder most recently served as chief legal officer and secretary of GW Pharmaceuticals . Earlier in his career, Snyder was general counsel and secretary at Actelion and Eisai . Back in July, Ideaya inked a $406.5 million deal with Biocytogen . → Deerfield Group has rolled out the welcome mat for two new execs: Guy Varady as EVP, integrated marketing and Bob Josefsberg as EVP, communications. Before this, Varady was SVP, management supervisor for DDB Health and held a number of roles at IPG Health and Omnicom Health Group . Meanwhile, Josefsberg was VP, corporate communications at Karuna Therapeutics and managing director at Chamberlain Healthcare Public Relations . → Tempest Therapeutics , which revealed early PFS and OS data for its liver cancer combo last October, has brought on Sheldon Mullins as VP, regulatory affairs. Mullins joins the team after gigs at Arrowhead Pharmaceuticals and Ardelyx . Earlier in his career, Mullins was with Anacor Pharmaceuticals , Onyx Pharmaceuticals and Genentech. In addition to Mullins’ appointment, Darrin Bomba and Henry Johnson have been promoted to the titles of VP, development operations and VP, CMC & medicinal chemistry, respectively. → Entrada Therapeutics CEO Dipal Doshi has picked up a seat on the board of directors at āshibio , a California biotech that will push its ex-Gilead drug andecaliximab into a Phase 2/3 study for patients with an ultra-rare bone disorder called fibrodysplasia ossificans progressiva (FOP). Āshibio came out of stealth mode this summer with a $40 million raise . → Akari Therapeutics , which is developing PAS-nomacopan for geographic atrophy, has elected former Epizyme CEO Rob Bazemore to the board of directors. Bazemore is also a board member at Ardelyx and Nuvation Bio .

高管变更上市批准临床3期并购IPO

2024-08-08

·CPHI制药在线

浅谈CD19靶向CAR-T疗法进展：又一国产报产，进军自免领域

关注并星标CPHI制药在线 7月20日，精准生物递交的「普基仑赛注射液」的上市申请获CDE受理。普基仑赛（pCAR-19B）是精准生物自主研发的一款针对CD19阳性B细胞起源的恶性血液系统疾病而开发的CAR-T细胞免疫治疗产品。因对CAR结构进行了优化，同时采用更为安全的基因转导载体系统，普基仑赛具有潜在更好的有效性和安全性。已公布的普基仑赛治疗儿童、青少年复发/难治性B细胞急性淋巴细胞白血病（B-ALL）的1期临床数据显示：9例入组患者均获得完全缓解(CR），总体缓解率达100%，且首次达到完全缓解（CR）的患者微小残留病变（MRD）也均为阴性；无剂量限制性毒性（DLT）和治疗相关死亡事件发生，总体安全性和耐受性良好。 2023年11月，pCAR-19B被CDE纳入拟突破性治疗品种，用于治疗3～21岁患有CD19阳性复发难治性急性淋巴细胞白血病。2024年6月底，pCAR-19B被CDE纳入优先审评，用于治疗3～21岁CD19阳性的复发或难治性B细胞急性淋巴细胞白血病。此次pCAR-19B申报的适应症大概率就是3～21岁患有CD19阳性复发难治性急性淋巴细胞白血病。此外，pCAR-19B还被开发用于治疗22-70岁CD19阳性复发/难治性B细胞急性淋巴细胞白血病。 CD19靶向CAR-T疗法赛道拥挤 CD19是CAR-T疗法的热门靶点。据不完全统计，目前全球监管机构已批准了6款CD19靶向CAR-T疗法，详见下表。这些疗法均被批准用于治疗恶性血液肿瘤，但仅Kymriah适应症覆盖儿童和成人复发或难治性B-ALL，这意味着pCAR-19B在3～21岁CD19阳性复发难治性ALL适应症的竞争并不十分激烈。从研发企业看，已获批的CD19靶向CAR-T疗法绝大多数被大型跨国药企（MNC）持有，其中吉利德占据两款。我国药企在CAR-T疗法领域进展较慢，仅一款全自主知识产权的CD19靶向CAR-T疗法获批上市。市场表现上，Yescarta表现最佳，2023年销售额达15亿美元。Kymriah次之，2023年销售额达5.08亿美元，不过其销售额从2022年开始下滑。Tecartus排第三，2023年销售额略高于Breyanzi（3.7亿美元 Vs 3.64亿美元），不过Breyanzi增幅明显。倍诺达排名第五，2023年销售额大约为1.74亿元。在研CD19靶向CAR-T疗法进展，两款已申请上市目前全球还有多款在研CD19靶向CAR-T疗法，详见下表。这些在研疗法中部分药物作用靶点不仅仅局限于CD19 ，还涉及BCMA、CD20等。而且，适应症也愈发广泛，除了恶性血液肿瘤，还包括多种自身免疫性疾病。研发进度上，obecabtagene autoleucel（Obe-cel）和普基仑赛进展相对较快，已申请上市。其中Obe-cel是Autolus Therapeutics开发的一种可快速解离CD19结合域的自体CD19 CAR-T，其独特之处在于设计的嵌合抗原受体在与CD19结合后具有较快的解离速度，能够尽量减少T细胞的过度激活，在降低毒副作用的同时，不易发生T细胞耗竭，提高CAR-T疗法的持久性。2024年5月，FDA受理Obe-cel治疗复发/难治性B-ALL成人患者的生物制品许可申请。 CAR039、GC007G和ssCART-19处于2期临床，其中C-CAR039是新型第二代4-1BB双靶点CAR-T产品，具有经优化的双特异性抗原结合结构域，可同时作用于CD19和CD20双靶点，可以在体内持续清除CD19/CD20单阳性或双阳性肿瘤细胞。2023 ASH上公布的C-CAR039治疗复发或难治性（R/R）B细胞非霍奇金淋巴瘤（B-NHL）的临床试验数据显示：在可评价的R/R NHL患者中，中位随访时间30.0个月，总缓解率为91.5%，完全缓解率为85.1%。 GC007g是亘喜生物旗下的一款靶向CD19的供者来源异基因CAR-T细胞疗法，用于治疗接受过同种异体干细胞移植后复发的B-ALL患者群体。在1期临床试验中，GC007g在有效性及安全性方面都取得了令人鼓舞的数据。 ssCART-19是优卡迪生物开发的第四代CAR-T产品，可同时表达CAR结构和IL-6沉默元件，可显著降低IL-6因子的释放水平，从而进一步降低单核细胞活化和促炎细胞因子的释放，从预防层面来减轻严重细胞因子释放综合征（CRS）和严重免疫效应细胞相关神经毒性综合征（ICANS）的发生率，从而提高CAR-T的用药安全性。2024年5月，ssCART-19被CDE纳入突破性治疗品种，用于治疗R/R ALL。 2024 EHA上公布的ssCART-19治疗R/R B-ALL的多中心1/2期临床试验数据显示：与cCART-19组ORR相比，ssCART-19组ORR较高，为91.49%（Vs 85%）。且ssCART-19组中位OS、中位PFS及6个月时PFS均显著高于cCART-19组。此外，ssCART-19组安全性明显优于cCART-19组，ssCART-19组AE的严重性、3级及以上AE的发生率低于cCART-19组。 CABA-201、YTB-323、KYV-101等处于1/2期临床，其中CABA-201是一款含有4-1BB共刺激域的CD19靶向CAR-T疗法，其CD19 binder由驯鹿生物独家授权。YTB323是诺华基于T-Charge平台所开发的靶向CD19的CAR-T细胞疗法，临床前研究显示：相比传统生产的CAR-T细胞，YTB323在更低的剂量下表现出增强的体内扩增和抗肿瘤活性。在治疗R/R DLBCL?的1期临床试验中，YTB323达到75%的完全缓解率。KQ-2003是一款从源头自主研发的新一代增强型双靶CAR-T产品，能同时靶向BCMA和CD19两个靶点。2024年3月，KQ-2003在国内获批临床，成为全球首款用于治疗POEMS综合征的CAR-T细胞疗法。 MC-1-50、GC012F处于1期临床，其中MC-1-50是精准生物自主研发的第二代靶向CD19的CAR-T细胞疗法，是一种新型更快、更有效的CAR-T制备方案，可以实现更低剂量、更小副作用、更持久的CAR-T产品。GC012F是一款基于亘喜生物专有的FasTCAR技术平台开发的BCMA/CD19双靶点自体CAR-T细胞疗法，有望变革性地为癌症和自身免疫性疾病治疗带来快速、深入且持久的效果，并具备差异化的安全性优势。总结作为CAR-T疗法的热门靶点，CD19靶点竞争激烈，获批产品数量达6款，2款已申请上市，超10款进入临床试验阶段。然而，目前CD19靶向CAR-T疗法市场几乎全被MNC占据，原研国产CD19靶向CAR-T疗法仅1款，且还仅在国内获批上市。在研疗法中，我国药企多有布局，但大多处于1、2期临床，距离未来获批上市还有很长的路要走。而且，我国药企开发的CD19靶向CAR-T疗法大多针对恶性血液肿瘤，这很容易造成适应症扎堆情况。国外药企在开发CD19靶向CAR-T疗法时适应症已开始往自身免疫性疾病方面布局，这值得我国药企借鉴。 END 【智药研习社直播预告】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~

细胞疗法免疫疗法ASH会议优先审批上市批准

100 项与 Obecabatagene autoleucel 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
复发性 B 细胞急性淋巴细胞白血病	申请上市	美国	Autolus Therapeutics Plc	2023-11-29
难治性 B 细胞急性淋巴细胞白血病	申请上市	美国	Autolus Therapeutics Plc	2023-11-29
前体B细胞急性淋巴细胞白血病	临床2期	-	Autolus Ltd.	2020-06-03
伯基特淋巴瘤	临床1期	美国	Autolus Ltd.	2023-11-16
伯基特淋巴瘤	临床1期	英国	Autolus Ltd.	2023-11-16
原发性中枢神经系统淋巴瘤	临床1期	英国	Autolus Ltd.	2022-01-30
慢性淋巴细胞白血病	临床1期	英国	University College London	2017-09-29
复发性成人急性淋巴细胞白血病	临床1期	英国	University College London	2017-09-29
小淋巴细胞淋巴瘤	临床1期	英国	University College London	2017-09-29
弥漫性大B细胞淋巴瘤	药物发现	英国	University College London	2016-06-01

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04404660 (FELIX, ASCO2024) 人工标引	临床1/2期	复发性 B 细胞急性淋巴细胞白血病 \| 难治性 B 细胞急性淋巴细胞白血病 CD19 binder	127	Obe-cel	觸窪衊艱鏇齋餘鬱衊醖(窪夢鬱鬱網鬱窪繭鑰積) = Pts who experienced B-cell recovery had a hazard risk of relapse or death 1.7 times compared with pts without B-cell recovery 構蓋鬱鹽築製繭衊遞製 (壓繭製壓顧襯選製壓窪 ) 更多	积极	2024-05-24
NCT04404660 (FELIX, ASCO2024) 人工标引	临床1/2期	复发性 B 细胞急性淋巴细胞白血病 \| 难治性 B 细胞急性淋巴细胞白血病 CD19 binder	127	Obe-cel (with censoring for consolidative SCT or new therapies)		积极	2024-05-24
NCT04404660 (FELIX, EHA2024) 人工标引	临床1/2期	前体B细胞急性淋巴细胞白血病	127	Obecabtagene autoleucel (obe-cel)	(膚蓋遞鑰鏇齋淵獵壓築) = 範遞選夢艱積簾艱壓廠淵鏇壓選齋觸膚鹽廠襯 (膚淵鏇糧範積壓淵鹹繭 ) 更多	积极	2024-05-23
NCT04404660 (FELIX, EHA2024) 人工标引	临床1/2期	复发性成人急性淋巴细胞白血病 \| 难治性成人急性淋巴细胞白血病	127	OBECABTAGENE AUTOLEUCEL (Bridging therapy with INO)	(製廠廠齋夢淵鹹範襯鏇) = 夢願範齋製餘顧觸餘醖鏇蓋範醖積鹽鑰構鏇淵 (積範廠鬱顧遞積襯鬱構, 4.1 ~ NE) 更多	积极	2024-05-14
NCT04404660 (FELIX, EHA2024) 人工标引	临床1/2期	复发性成人急性淋巴细胞白血病 \| 难治性成人急性淋巴细胞白血病	127	OBECABTAGENE AUTOLEUCEL (Bridging therapy without INO)	(製廠廠齋夢淵鹹範襯鏇) = 窪顧夢遞鏇淵鏇淵鹹夢鏇蓋範醖積鹽鑰構鏇淵 (積範廠鬱顧遞積襯鬱構, 6.0 ~ NE) 更多	积极	2024-05-14
NCT04404660 (FELIX, EHA2024)	临床1/2期	难治性 B 细胞急性淋巴细胞白血病 CD19 chimeric antigen receptor (CAR)	127	OBECABTAGENE AUTOLEUCEL	鬱餘觸觸醖觸遞襯築糧(繭選膚窪壓蓋鑰範衊願) = 壓膚觸鹹膚醖夢壓壓簾範鬱壓鏇繭醖願窪製衊 (夢蓋鹹餘構膚構鬱鏇選 )	积极	2024-05-14
NCT04404660 (FELIX, EHA2024)	临床1/2期	难治性 B 细胞急性淋巴细胞白血病 CD19 chimeric antigen receptor (CAR)	127	OBECABTAGENE AUTOLEUCEL	鬱餘觸觸醖觸遞襯築糧(繭選膚窪壓蓋鑰範衊願) = 艱壓鏇製艱醖鬱獵憲願範鬱壓鏇繭醖願窪製衊 (夢蓋鹹餘構膚構鬱鏇選 )	积极	2024-05-14
FELIX (ASH2023)	N/A	-	90	Obe-cel	鹹觸選網鹹齋簾觸窪鏇(願淵鏇餘淵構鑰鹽衊選) = 鹹網鏇襯齋鬱齋衊襯襯簾衊淵簾窪襯顧餘構衊 (願構齋鹹膚顧鬱範鬱艱 ) 更多	-	2023-12-11
ALLCAR19 and FELIX Phase Ib Studies (ASH2023)	临床1/2期	复发性 B 细胞急性淋巴细胞白血病 \| B细胞白血病	-	Obecabtagene Autoleucel	蓋蓋窪積繭觸窪積繭簾(餘艱顧構獵鏇築蓋觸夢) = Of the 11 long-term R/R B-ALL responders who had not received consolidation allo-HSCT, 10 have ongoing B-cell aplasia. Of the 14 ongoing responders in the R/R B-CLL/B-NHL cohort, 12 have ongoing B-cell aplasia (<20 B cells/µl). Of note, ongoing B-cell aplasia did not correlate with an increased risk of late serious infection. No other long-term toxicity ascribed to obe-cel was reported. 憲構廠糧鏇鹹蓋選網繭 (糧鬱鏇願鏇艱範憲衊願 )	-	2023-12-09
NCT04404660 (FELIX, ASH2023)	临床1/2期	复发性成人急性淋巴细胞白血病	152	Obecabtagene Autoleucel (obe-cel)	廠簾憲觸淵廠構憲廠製(襯廠製廠遞簾廠壓鏇齋) = 願鹽願襯醖壓繭簾鹽簾襯糧觸鹹齋襯鑰顧鹽選 (鏇簾鑰衊獵齋憲遞鏇製 ) 更多	-	2023-12-09
FELIX (NEWS) 人工标引	临床2期	-	94	obecabtagene autoleucel	(鑰獵醖範夢製鹽糧選構) = 製遞膚艱蓋鹽範鏇壓淵糧膚範夢鑰蓋衊醖壓廠 (壓夢鬱醖遞壓遞範齋淵 )	积极	2023-11-29
FELIX (NEWS) 人工标引	临床2期	-	94	obecabtagene autoleucel (获得缓解的患者)	(繭醖蓋壓網齋鏇選繭顧) = 襯觸廠衊蓋壓廠膚積餘網築構鑰襯鬱構鑰齋鬱 (觸蓋鬱窪鏇醖鏇構願範 ) 更多	积极	2023-11-29
NCT04404660 (FELIX, EHA2023)	临床2期	难治性 B 细胞急性淋巴细胞白血病	92	OBECABTAGENE AUTOLEUCEL (OBE-CEL) (Obe-cel)	(醖糧鏇鏇窪糧蓋製鹽壓) = 鹽鑰積鏇鏇壓窪築願構憲壓築廠淵顧壓糧淵積 (襯顧顧憲構積遞鹽淵築, [55% ~ 82%]) 更多	-	2023-06-08
NCT04404660 (FELIX, ASCO2023) 人工标引	临床1/2期	CD19阳性B细胞急性淋巴细胞白血病	92	obecabtagene autoleucel	(蓋簾蓋簾築壓願餘齋願) = Other common Grade≥3 adverse events regardless of causality were febrile neutropenia (25%) and anaemia (20%). 鬱繭網觸積範鑰積顧夢 (構簾蓋範積蓋積蓋鹽淵 )	积极	2023-05-31