A Phase I/II Study of Natalizumab as a Single Agent in Children, Adolescents and Young Adults With Recurrent, Refractory or Progressive Pulmonary Metastatic Osteosarcoma

The purpose of this study is to evaluate the safety and tolerability of Natalizumab in children, adolescent and young adult patients with pulmonary metastatic osteosarcoma (pOS) and to assess clinical response associated with this treatment as well as overall survival.

开始日期2024-06-01

申办/合作机构

The Case Comprehensive Cancer Center

NCT05658497 / RecruitingN/A

Vumerity (Diroximel Fumarate) Prospective MS Pregnancy Exposure Registry

The primary objectives of the study are to estimate the risk of major congenital malformations (MCMs) in infants born to women with multiple sclerosis (MS) who were exposed to diroximel fumarate (DRF) at any time from 2 weeks after the first day of their last menstrual period (LMP) up through the first trimester of pregnancy and to comparatively evaluate pregnancy outcomes with MCMs in women with MS who were exposed to DRF at any time from 2 weeks after the first day of their LMP through the first trimester of pregnancy with the following: i) women with MS who were unexposed to disease modifying therapies (DMTs) and, ii) women with MS who were exposed to other DMTs (e.g., Avonex and Tysabri Pregnancy Registries).
The secondary objective of the study is to evaluate pregnancy outcomes in women with DRF exposure at any time from 2 weeks after the first day of their LMP through the end of pregnancy compared with the following: i) women with MS who were unexposed to DMTs, ii) women with dimethyl fumarate (DMF) exposure, iii) women with MS who were exposed to other DMTs (e.g., Avonex and Tysabri Pregnancy Registries), and iv) women without MS (e.g., women from external, general population comparators).

开始日期2023-10-27

申办/合作机构

Biogen, Inc.

NCT05618301 / Recruiting临床1期IIT

A Pilot Safety and Feasibility Study to Evaluate Motixafortide (CXCR4/SDF-1 Inhibition) and Natalizumab (VLA-4/VCAM-1 Inhibition) as a Novel Regimen to Mobilize CD34+ Hematopoietic Stem Cells for Gene Therapies in Sickle Cell Disease (SCD)

Hematopoietic stem cell (HSC)-based gene therapies now offer curative potential for patients with sickle cell disease (SCD), with decreased toxicity compared to allogeneic hematopoietic cell transplantation. However, effective HSC-based gene therapy depends on collecting sufficient HSCs to generate the therapeutic product, and currently available mobilization regimens carry unacceptable risk for patients with SCD or do not reliably yield optimal numbers of HSCs for gene therapy.
The investigators hypothesize that HSC mobilization with motixafortide (CXCR4i) alone and the combination of motixafortide plus natalizumab (VLA-4i) will be safe and tolerable in SCD patients. In addition, the investigators hypothesize that combined CXCR4 and VLA-4 blockade with motixafortide plus natalizumab will result in a rapid, robust, and synergistic increase in HSC mobilization to peripheral blood (PB) in patients with SCD, when compared to motixafortide alone.

开始日期2023-07-07

申办/合作机构

Washington University School of Medicine

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100 项与那他珠单抗相关的专利（医药）

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2,838

项与那他珠单抗相关的文献（医药）

2024-12-31·Journal of Medical Economics

Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom

Article

作者: Karabudak, R ; Horakova, D ; Girard, M ; Castillo-Triviño ; Hodgkinson, S ; Gerlach, O ; Gray, O ; Cartechini, E ; de Gans, K ; McCombe, P ; Spitaleri, D ; Solaro, C ; Garber, J ; Sas, A ; Alroughani, R ; Duquette, P ; Ramo-Tello, C ; Prevost, J ; van Pesch, V ; Skibina, O ; Van Wijmeersch, B ; Patti, F ; Aguera Morales, E ; Oreja-Guevara ; Laureys, G ; van der Walt, A ; Shaygannejad, V ; John, N ; Spelman, T ; Gouider, R ; Rajda, C ; Csepany, T ; Izquierdo, G ; Grand'Maison, F ; Trojano, M ; Onofrj, M ; Ozakbas, S ; Jose Sa, M ; Hughes, S ; Soysal, A ; Buzzard, K ; Havrdova, E K ; De Luca, G ; Eichau, S ; Herring, W L ; Butzkueven, H ; Slee, M ; Iuliano, G ; Jokubaitis, V G ; Petersen, T ; Acosta, C ; Lugaresi, A ; Hyde, R ; Pucci, E ; Ferraro, D ; Sanchez-Menoyo, J L ; Moore, F ; Kalincik, T ; Rozsa, C ; Terzi, M ; Granella, F ; Simo, M ; Ampapa, R ; Fragoso, Y ; Bergamaschi, R

AIM:

To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS).

METHODS:

Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups. Comparative effectiveness results were used in a cost-effectiveness model comparing natalizumab and fingolimod, using an established Markov structure over a lifetime horizon with health states based on the Expanded Disability Status Scale. Additional model data sources included the UK MS Survey 2015, published literature, and publicly available sources.

RESULTS:

In the comparative effectiveness analysis, we found a significantly lower ARR for patients starting natalizumab compared with fingolimod (rate ratio [RR] = 0.65; 95% confidence interval [CI], 0.57-0.73) or BRACETD (RR = 0.46; 95% CI, 0.42-0.53). Similarly, CDI6M was higher for patients starting natalizumab compared with fingolimod (hazard ratio [HR] = 1.25; 95% CI, 1.01-1.55) and BRACETD (HR = 1.46; 95% CI, 1.16-1.85). In patients starting fingolimod, we found a lower ARR (RR = 0.72; 95% CI, 0.65-0.80) compared with starting BRACETD, but no difference in CDI6M (HR = 1.17; 95% CI, 0.91-1.50). Differences in CDW6M were not found between the treatment groups. In the base-case cost-effectiveness analysis, natalizumab dominated fingolimod (0.302 higher quality-adjusted life-years [QALYs] and £17,141 lower predicted lifetime costs). Similar cost-effectiveness results were observed across sensitivity analyses.

CONCLUSIONS:

This MSBase Registry analysis suggests that natalizumab improves clinical outcomes when compared with fingolimod, which translates to higher QALYs and lower costs in UK patients with RES-RRMS.

2024-02-13·Neurology

Adverse Events Associated With Disease-Modifying Drugs for Multiple Sclerosis

Article

作者: Fisk, John D ; Zhu, Feng ; Ekuma, Okechukwu ; Yao, Shenzhen ; Marrie, Ruth Ann ; Zhao, Yinshan ; Ng, Huah Shin ; Lu, Xinya ; Tremlett, Helen ; Evans, Charity

BACKGROUND AND OBJECTIVES:

It is not possible to fully establish the safety of a disease-modifying drug (DMD) for multiple sclerosis (MS) from randomized controlled trials as only very common adverse events occurring over the short-term can be captured, and the quality of reporting has been variable. We examined the relationship between the DMDs for MS and potential adverse events in a multiregion population-based study.

METHODS:

We identified people with MS using linked administrative health data from 4 Canadian provinces. MS cases were followed from the most recent of first MS or related demyelinating disease event on January 1, 1996, until the earliest of emigration, death, or December 31, 2017. DMD exposure primarily comprised β-interferon, glatiramer acetate, natalizumab, fingolimod, dimethyl fumarate, teriflunomide, and alemtuzumab. We examined associations between DMD exposure and infection-related hospitalizations and physician visits using recurrent events proportional means models and between DMD exposure and 15 broad categories of incident adverse events using stratified multivariate Cox proportional hazard models.

RESULTS:

We identified 35,894 people with MS. While virtually all DMDs were associated with a 42%-61% lower risk of infection-related hospitalizations, there was a modest increase in infection-related physician visits by 10%-33% for select DMDs. For incident adverse events, most elevated risks involved a second-generation DMD, with alemtuzumab's hazard of thyroid disorders being 19.42 (95% CI 9.29-36.51), hypertension 4.96 (95% CI 1.78-13.84), and cardiovascular disease 3.72 (95% CI 2.12-6.53). Natalizumab's highest risk was for cardiovascular disease (adjusted hazard ratio [aHR] 1.61; 95% CI 1.24-2.10). For the oral DMDs, fingolimod was associated with higher hazards of cerebrovascular (aHR 2.04; 95% CI 1.27-3.30) and ischemic heart diseases (aHR 1.64; 95% CI 1.10-2.44) and hypertension (aHR 1.73; 95% CI 1.30-2.31); teriflunomide with higher hazards of thyroid disorders (aHR 2.30; 95% CI 1.11-4.74), chronic liver disease (aHR 1.94; 95% CI 1.19-3.18), hypertension (aHR 1.76; 95% CI 1.32-2.37), and hyperlipidemia (aHR 1.61; 95% CI 1.07-2.44); and from complementary analyses (in 1 province), dimethyl fumarate with acute liver injury (aHR 6.55; 95% CI 1.96-21.87).

DISCUSSION:

Our study provides an extensive safety profile of several different DMDs used to treat MS in the real-world setting. Our findings not only complement those observed in short-term clinical trials but also provide new insights that help inform the risk-benefit profile of the DMDs used to treat MS in clinical practice. The results of this study highlight the continued need for long-term, independent safety studies of the DMDs used to treat MS.

CLASSIFICATION OF EVIDENCE:

This study provides Class III evidence that for patients with MS, while DMD exposure reduces the risk of infection-related hospitalizations, there are increased risks of infection-related physician visits and incident adverse events for select DMDs.

2024-02-01·Multiple Sclerosis and Related Disorders

Quantifying the administration and monitoring time burden of several disease-modifying therapies for relapsing multiple sclerosis in the United Kingdom: A time and motion study

Article

作者: Amin, Amerah ; De Cock, Erwin ; Ashton, Luke ; Lowndes, Claire ; Pendlebury, Jessica ; Kalra, Seema ; Leclerc, Stephanie ; Evans, Hannah ; Brownlee, Wallace ; Barker, Noreen ; Carod-Artal, Francisco Javier ; Rog, David

BACKGROUND:

The treatment landscape for relapsing multiple sclerosis (MS) has changed dramatically in recent decades, including an increasing number of high-efficacy disease-modifying therapies (DMTs) with varied administration and monitoring requirements. Coupled with greater focus on earlier treatment, these factors have resulted in stretching of the capacity of MS specialist services and allied healthcare professionals (HCPs). To assist with the effective planning of MS services in the UK NHS, this study quantified the administration and monitoring time burden associated with high-efficacy DMTs (alemtuzumab, cladribine tablets, fingolimod, natalizumab, and ocrelizumab) for relapsing MS.

METHODS:

A Time and Motion (T&M) study was conducted across four MS centres in the UK, over 3-4 months per centre (Aug 2019-Feb 2021). Time dedicated by HCPs (including but not limited to neurologists, MS specialist nurses, infusion nurses, and healthcare assistants) to pre-specified drug administration and monitoring activities, elicited during pre-study interviews at each centre, was assessed for each of the selected DMTs. Administration activities included: installing peripheral access; pre-medication administration (if needed); preparing drug for infusion; infusion initiation, monitoring, and disconnection; and patient monitoring post-infusion. Monitoring activities included: booking appointments for blood draws; blood draw; retrieval and review of blood results; maintaining blood records and follow-up with the patient; checking availability of MRI results and follow-up with the patient; booking appointments for neurologist or nurse consultations; and checking patient files prior to clinic visits. A T&M model was built using observational T&M study results, data obtained through pre-study interviews, as well as stipulated monitoring intervals from relevant Summaries of Product Characteristics for the selected DMTs, to estimate active HCP time with each DMT, extrapolated over a period of 4 years per-patient.

RESULTS:

For oral DMTs, projected total active HCP time (monitoring only) per-patient over 4 years was 14.7 h for cladribine tablets and 19.2 h for fingolimod. For infused DMTs, total time (administration and monitoring) for alemtuzumab was 37.7 h (6.0 and 31.6 h, respectively), 48.1 h for natalizumab (17.4 and 30.8 h, respectively), and 23.5 h for ocrelizumab (6.1 and 17.4 h, respectively).

CONCLUSIONS:

While active HCP time varied across centres, infused DMTs were projected to require the greatest amount of HCP time associated with administration and monitoring over 4 years versus oral DMTs. These findings may assist MS-specific HCPs in planning and delivering the equitable provision of DMT services for patients with relapsing MS.

155

项与那他珠单抗相关的新闻（医药）

2024-04-04

·PRNewswire

Cadenza Bio, Inc. Appoints Michael A. Panzara, MD, MPH, to its Board of Directors

OKLAHOMA CITY, April 4, 2024 /PRNewswire/ -- Cadenza Bio, Inc., a pioneering preclinical biotechnology company dedicated to developing innovative small-molecule drugs for the treatment of multiple sclerosis (MS) and other demyelinating and inflammatory diseases, proudly announces the appointment of Michael A. Panzara, MD, MPH, to its esteemed board of directors. Dr. Panzara brings over 22 years of invaluable biopharmaceutical experience to Cadenza Bio. He currently serves as chief medical officer at Neurvati Neurosciences, a neuroscience-focused biotechnology company working to advance the development of clinical-stage product candidates for neurological and neuropsychiatric disorders. Prior to his role at Neurvati, Dr. Panzara held key leadership positions at Wave Life Sciences, Sanofi, Genzyme, and Biogen, showcasing his deep understanding of neurological disorders and drug development. He also serves on the board of directors of Athira Pharma, Inc., a neurology-focused clinical-stage biopharmaceutical company. Over his career, Dr. Panzara oversaw development activities and global regulatory approvals for several MS drugs. He served as the head of the Multiple Sclerosis, Neurology, and Ophthalmology Therapeutic Area for Global Development at Sanofi Genzyme, where he oversaw global regulatory approvals of LEMTRADA® (alemtuzumab) and AUBAGIO® (teriflunomide) and was responsible for development strategy and oversight within these therapeutic areas. During his time at Biogen, he served as global clinical lead for the development of TYSABRI® (natalizumab) for MS and managed clinical development activities for all late-stage MS products including AVONEX® (interferon beta-1a), PLEGRIDY® (PEG-interferon beta-1a), and TECFIDERA® (dimethylfumarate). "We are delighted to welcome Dr. Panzara to our board of directors," said Dr. Carol Curtis, chief executive officer of Cadenza Bio. "His extensive experience in developing therapies for MS and other neurological disorders aligns perfectly with our mission at Cadenza Bio. Dr. Panzara's strategic insights and deep understanding of the industry will be invaluable as we continue to advance our innovative drug pipeline and work towards bringing transformative treatments to patients in need." Dr. Panzara received his undergraduate degree in biology from the University of Pennsylvania and his medical degree from Stanford University School of Medicine. He completed his neurology training at Massachusetts General Hospital and received postdoctoral training in immunology and rheumatology at Brigham and Women's Hospital. Additionally, Dr. Panzara earned his master of public health degree from the Harvard School of Public Health. With Dr. Panzara joining the board of directors, Cadenza Bio is in a stronger position to achieve its goal of developing groundbreaking therapies for MS and other demyelinating and inflammatory diseases. "I look forward to joining the board of directors at Cadenza Bio at such an exciting time in the growth of the company," said Dr. Panzara. "Their approach in developing innovative dual-action therapeutic agents with neuroprotective and immunomodulatory effects has great potential to significantly expand our ability to address the unmet needs that remain for many MS patients." For more information about Cadenza Bio and its groundbreaking research, please visit . About Cadenza Bio, Inc. Cadenza Bio, Inc. is a preclinical biotechnology company focused on developing innovative small-molecule drugs for the treatment of demyelinating and inflammatory diseases. The company's mission is to break the cycle of disease and transform lives by developing therapies that not only alleviate symptoms but also halt progression, promote repair, and restore quality of life for patients. Cadenza Bio's MS drug pipeline, emerging from a collaboration between leading researchers, demonstrates promising preclinical results and offers hope for patients suffering from these debilitating conditions. SOURCE Cadenza Bio, Inc.

高管变更

2024-03-26

·BioSpace

BioLineRx Reports 2023 Financial Results and Recent Corporate and Portfolio Updates

Reported significant commercial progress for APHEXDA® -- secured payer coverage representing ~95% of covered lives in the U.S.; continued progress on formulary approvals at targeted major transplant centers; received Healthcare Common Procedure Coding System (HCPCS) J-Code to facilitate Medicare reimbursement Announced first patient dosed in randomized Phase 2b clinical trial evaluating motixafortide in first-line pancreatic cancer Continued to support partner Gloria Biosciences in plans to execute pivotal bridging study of motixafortide in stem cell mobilization and Phase 2b randomized study in first-line pancreatic cancer in China Management to host conference call today, March 26, at 8:30 am EDT TEL AVIV, Israel, March 26, 2024 /PRNewswire/ -- BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a commercial stage biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases, today reported its financial results for the year ended December 31, 2023, and provided recent corporate and portfolio updates. "Following FDA approval of APHEXDA® in September, physicians and transplant centers have been very receptive to the value of our strong clinical data, and our commercial team has made substantial progress establishing relationships with transplant centers across the country," said Philip Serlin, Chief Executive Officer of BioLineRx. "This year will continue to be primarily a foundational period for the commercialization of APHEXDA. We are seeing substantial progress on Pharmacy & Therapeutics committee approvals -- the first step toward center adoption -- and are actively supporting centers as they build usage protocols and treat their first patients. Initial feedback on patient experiences has been positive, and we are already seeing repeat purchases. Notably, we have achieved payer coverage representing approximately 95% of covered lives in the U.S. to date, which we believe reflects the value that APHEXDA offers to payers and patients alike, particularly its ability to mobilize the targeted number of stem cells in fewer apheresis sessions. "Additionally, through a clinical collaboration with Washington University, we are actively evaluating the potential of motixafortide to support gene therapy for patients with sickle cell disease, a treatment process that requires significant quantities of hematopoietic stem cells. We anticipate data from this proof-of-concept Phase 1 study in patients with sickle cell disease in the second half of this year. "At the same time, we are making significant progress advancing clinical programs evaluating motixafortide in pancreatic cancer, which if ultimately approved in combination with PD-1 inhibitors, would serve a much larger patient population and provide confidence for expanding into additional solid tumors. In pancreatic cancer, our enthusiasm is bolstered by the compelling data presented last fall from the single-arm pilot phase of the Phase 2b trial sponsored by Columbia University. The first patient has now been dosed in the randomized Phase 2b portion of that study, and we are also working with Gloria Biosciences on the design and execution of a similar randomized Phase 2b combination trial of motixafortide and zimberelimab in pancreatic cancer in China. "Our vision of bringing a best-in-class stem cell mobilization agent to market, as well as advancing development in pancreatic cancer and other solid tumor areas with major unmet needs, is being actively realized. We look forward to the exciting, continued execution progress that our commercial and development teams will make this year," Mr. Serlin concluded. Corporate Updates Launched APHEXDA (motixafortide) in the U.S. Announced closing of exclusive license agreement that includes development and commercialization rights to motixafortide across all indications in the Asia region, as well as a strategic equity investment Strengthened motixafortide intellectual property estate with notice of allowance for U.S. patent covering method of manufacturing motixafortide suitable for large scale production; the patent supplements existing Orphan Drug Designation in the U.S. and Europe for the treatment of pancreatic cancer, as well as Orphan Drug market exclusivity for autologous stem cell mobilization in multiple myeloma patients in the U.S. following last year's FDA approval of APHEXDA APHEXDA Launch Updates Reported positive coverage decisions by payers representing ~95% of all covered lives in the U.S. Received inclusion of APHEXDA in the National Comprehensive Cancer Network (NCCN) guidelines for Hematopoietic Cell Transplantation Achieved "on formulary" status for APHEXDA within targeted top 80 transplantation centers (which perform 85% of all U.S. transplants) managing ~20% of stem cell transplant procedures at these institutions; anticipate similar on formulary status of ~35% at end of Q2 2024 and ~60% at year-end 2024 Received Healthcare Common Procedure Coding System (HCPCS) J-Code to facilitate Medicare reimbursement for APHEXDA to transplant centers treating Medicare beneficiaries Clinical Portfolio Updates Motixafortide (selective inhibitor of CXCR4 chemokine receptor) Multiple Myeloma Presented posters at both the American Society of Hematology (ASH) 65th Annual Meeting on December 10, 2023, and the 2024 Tandem Meetings on February 21-24, 2024. The posters reviewed combination premedication benefits in the Phase 3 GENESIS trial, extended PD effect of elevated CD34+ cells in peripheral blood, and a post-hoc subgroup analysis of impaired HSC mobilization patients that demonstrated a consistent benefit of motixafortide + G-CSF over placebo + G-CSF mobilization for all patients Supported collaboration partner Gloria Biosciences with stem cell mobilization bridging study IND filing in February with the Center for Drug Evaluation of the National Medical Products Administration in China. Anticipate regulatory action in May 2024 and initiation of pivotal clinical trial in 2H 2024 Pancreatic Ductal Adenocarcinoma (mPDAC) Announced first patient dosed in a randomized, investigator-initiated Phase 2b clinical trial in collaboration with Columbia University assessing motixafortide in combination with the PD-1 inhibitor cemiplimab and standard-of-care chemotherapy as first-line treatment in patients with metastatic pancreatic cancer Advanced plans with collaboration partner Gloria Biosciences on a Phase 2b randomized clinical trial in China assessing motixafortide in combination with the PD-1 inhibitor zimberelimab and standard-of-care chemotherapy as first-line treatment in patients with metastatic pancreatic cancer. Anticipate clinical trial initiation in 2025 Sickle Cell Disease (SCD) & Gene Therapy Continued to enroll patients into a clinical trial in collaboration with Washington University School of Medicine in St. Louis to evaluate motixafortide as monotherapy and in combination with natalizumab for stem cell mobilization for gene therapies in sickle cell disease. Anticipate data in 2H 2024 Financial Results for Year Ended December 31, 2023 Total revenues for the year ended December 31, 2023, were $4.8 million, compared to no revenues for the year ended December 31, 2022. Revenues in 2023 (all of which were recorded in the fourth quarter) primarily reflect a portion of the upfront payment from the Gloria Biosciences license agreement, of which $4.6 million was recognized in 2023, as well as $0.2 million of revenues from product sales of APHEXDA in the U.S. Cost of revenues for the year ended December 31, 2023, amounted to $3.7 million, compared to no cost of revenues for the year ended December 31, 2022. The cost of revenues in 2023 (all of which was recorded in the fourth quarter) primarily reflects a $3.0 million sub-license fee to the upstream licensor of motixafortide payable on closing of the exclusive license agreement in Asia, as well as amortization of an intangible asset in respect of these license revenues in the amount of $0.5 million. Cost of product sales were insignificant, representing approximately 6% of related sales. Research and development expenses for the year ended December 31, 2023, were $12.5 million, compared to $17.6 million for the year ended December 31, 2022. The decrease resulted primarily from lower expenses related to motixafortide NDA supporting activities, as well as lower expenses associated with completion of the AGI-134 study Sales and marketing expenses for the year ended December 31, 2023, were $25.3 million, compared to $6.5 million for the year ended December 31, 2022. The increase resulted primarily from the ramp-up of pre-commercialization and commercialization activities related to motixafortide General and administrative expenses for the year ended December 31, 2023, were $6.3 million, compared to $5.1 million for the year ended December 31, 2022. The increase resulted primarily from an increase in payroll and related expenses associated with a small headcount increase during the 2022 period, as well as an increase in professional services and legal expenses Non-operating expenses for the year ended December 31, 2023, were $10.8 million, compared to non-operating income of $5.7 million for the year ended December 31, 2022. Non-operating expenses and income primarily relate to the non-cash revaluation of outstanding warrants resulting from changes in the company's share price during the respective periods Net loss for the year ended December 31, 2023 was $60.6 million, compared to $25.0 million for the year ended December 31, 2022. The net loss for 2023 included $17.8 million in non-cash expenses, specifically an expense of $11.1 million for the revaluation of warrants and a one-time $6.7 million impairment of intangible assets associated with discontinuation of the AGI-134 development program. The net loss for 2022 included $6.4 million in non-cash income specifically related to the revaluation of warrants. As of December 31, 2023, the Company had cash, cash equivalents, and short-term bank deposits of $43.0 million. The Company anticipates that this amount and other available resources, including amounts available under a debt facility with Kreos Capital, will be sufficient to fund operations, as currently planned, into 2025 A copy of the Company's annual report on Form 20-F for the year ended December 31, 2023 has been filed with the U.S. Securities and Exchange Commission at and posted on the Company's investor relations website at Company will deliver a hard copy of its annual report, including its complete audited consolidated financial statements, free of charge, to its shareholders upon request at IR@BioLineRx.com. Conference Call and Webcast Information To access the conference call, please dial +1-888-281-1167 from the U.S. or +972-3-918-0685 internationally. A live webcast and a replay of the call can be accessed through the event page on the Company's website. Please allow extra time prior to the call to visit the site and download any necessary software to listen to the live broadcast. The call replay will be available approximately two hours after completion of the live conference call. A dial-in replay of the call will be available until March 28, 2024; please dial +1-888-295-2634 from the US or +972-3-925-5904 internationally. About BioLineRx BioLineRx Ltd. (NASDAQ/TASE: BLRX) is a commercial stage biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases. The company's first approved product is APHEXDA® (motixafortide) with an indication in the U.S. for stem cell mobilization for autologous transplantation in multiple myeloma. BioLineRx is advancing a pipeline of investigational medicines for patients with sickle cell disease, pancreatic cancer, and other solid tumors. Headquartered in Israel, and with operations in the U.S., the company is driving innovative therapeutics with end-to-end expertise in development and commercialization, ensuring life-changing discoveries move beyond the bench to the bedside. Learn more about who we are, what we do, and how we do it at , or on Twitter and LinkedIn. Forward Looking Statement Various statements in this release concerning BioLineRx's future expectations constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include words such as "anticipates," "believes," "could," "estimates," "expects," "intends," "may," "plans," "potential," "predicts," "projects," "should," "will," and "would," and describe opinions about future events. These include statements regarding management's expectations, beliefs and intentions regarding, among other things, the potential benefits of APHEXDA, the execution of the launch of APHEXDA and the plans and objectives of management for future operations and expectations and commercial potential of motixafortide, as well as its potential investigational uses. These forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause the actual results, performance or achievements of BioLineRx to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Factors that could cause BioLineRx's actual results to differ materially from those expressed or implied in such forward-looking statements include, but are not limited to: the initiation, timing, progress and results of BioLineRx's preclinical studies, clinical trials, and other therapeutic candidate development efforts; BioLineRx's ability to advance its therapeutic candidates into clinical trials or to successfully complete its preclinical studies or clinical trials; whether BioLineRx's collaboration partners will be able to execute on collaboration goals in a timely manner; whether the clinical trial results for APHEXDA will be predictive of real-world results; BioLineRx's receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings and approvals; the clinical development, commercialization and market acceptance of BioLineRx's therapeutic candidates, including the degree and pace of market uptake of APHEXDA for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients; whether access to APHEXDA is achieved in a commercially viable manner and whether APHEXDA receives adequate reimbursement from third-party payors; BioLineRx's ability to establish, operationalize and maintain corporate collaborations; BioLineRx's ability to integrate new therapeutic candidates and new personnel; the interpretation of the properties and characteristics of BioLineRx's therapeutic candidates and of the results obtained with its therapeutic candidates in preclinical studies or clinical trials; the implementation of BioLineRx's business model and strategic plans for its business and therapeutic candidates; the scope of protection BioLineRx is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; estimates of BioLineRx's expenses, future revenues, capital requirements and its needs for and ability to access sufficient additional financing, including any unexpected costs or delays in the commercial launch of APHEXDA; risks related to changes in healthcare laws, rules and regulations in the United States or elsewhere; competitive companies, technologies and BioLineRx's industry; statements as to the impact of the political and security situation in Israel on BioLineRx's business; and the impact of the COVID-19 pandemic, the Russian invasion of Ukraine, the declared war by Israel against Hamas and the military campaigns against Hamas and other terrorist organizations, which may exacerbate the magnitude of the factors discussed above. These and other factors are more fully discussed in the "Risk Factors" section of BioLineRx's most recent annual report on Form 20-F filed with the Securities and Exchange Commission on March 26, 2024. In addition, any forward-looking statements represent BioLineRx's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. BioLineRx does not assume any obligation to update any forward-looking statements unless required by law. Contacts: United States John Lacey BioLineRx IR@biolinerx.com Israel Moran Meir LifeSci Advisors, LLC moran@lifesciadvisors.com Logo - View original content: SOURCE BioLineRx Ltd. Company Codes: NASDAQ-SMALL:BLRX, TelAviv:BLRX

临床结果引进/卖出临床2期ASH会议上市批准

2024-03-14

·赛柏蓝

2024年专利悬崖Top10品种

编者按：本文来自药智头条，作者葵花籽；赛柏蓝授权转载，编辑yuki“专利悬崖”意指药品专利保护期届满后，其销售额与利润大幅下滑的现象。此种现象如同一道无形的悬崖，原研药即便在光辉成就之下，亦无法回避这一严峻现实。对于原研药企而言，在寻求新增长点与巩固专利“护城河”的过程中，均面临着诸多挑战。利拉鲁肽、达沙替尼、那他珠单抗等多款年销售额超5亿美元的大品种都将在今年先后失去美国专利保护。2024年在美专利到期的十大药物资料来源：Fierce Pharma01 达沙替尼（Sprycel）适应症：慢性粒细胞白血病研发企业：BMS2023年美国销售额：14.5亿美元生物类似药上市时间：2024年9月达沙替尼是百时美施贵宝（BMS）肿瘤学主打产品之一，是一种针对癌细胞中特定蛋白质并阻止癌细胞生长的药物。BMS财报显示，达沙替尼2023年全球销售额约为19.3亿美元，其中14.5亿美元来自美国市场。达沙替尼于2006年首次获FDA批准，用于对先前治疗药物（包括伊马替尼）具有耐药性或不耐受的费城染色体阳性慢性髓系白血病慢性期（Ph+CML-CP）成人患者以及用于对先前治疗药物具有耐药性或不耐受的Ph+ALL成人患者。BMS在一份年度证券文件中解释说，由于与Apotex和一些未披露名称的公司达成了和解协议，某些仿制药获准在2024年9月上市，或在某些情况下提前上市。据悉，目前Teva、Biocon、Lupin、Dr.Reddy's Laboratories、Alebmic的仿制药已获得FDA暂定批准。02那他珠单抗（Tysabri）适应症：多发性硬化症、克罗恩病研发企业：渤健2023年美国销售额：9.98亿美元生物类似药上市时间：2024年下半年那他珠单抗于2004年获得FDA批准用于治疗多发性硬化症，2008年获批用于治疗克罗恩病。该药在2009年销售额高达11亿美元。根据渤健2023年第四季度财报，2023年该药在美国的销售额为9.98亿美元，较2022年的11.2亿美元下降约11%。在特拉华州联邦法院驳回百健对山德士的专利侵权诉讼约两个月后，山德士于2023年8月获得了美国首个、也是迄今为止唯一一个那他珠单抗生物类似药的批准。03米拉贝隆（Myrbetriq）适应症：膀胱过度活动症研发企业：安斯泰来2023年美国销售额：6.4亿美元生物类似药上市时间：2024年5月2012年6月，米拉贝隆在美国获批上市。2023年6月，美国特拉华州地区法院作出裁决，宣布该药2030年的一项关键专利无效，这促使安斯泰来公开回应，并强调该药在2024年5月前仍受专利保护。不久之后，安斯泰来又获得了一项2030年的膀胱过度活动症药物专利，并发起了新一轮针对仿制药公司的诉讼。安斯泰来寻求获得FDA禁令，禁止生物类似药在该专利到期前上市。FDA的桔皮书显示，米拉贝隆的监管专属期将于2024年9月到期。该药的部分专利将于2024年5月到期。与此同时，Lupin和Alkem两家公司的米拉贝隆仿制药已获得FDA批准，此外，Aurobindo的仿制药也获得了初步批准。04利拉鲁肽（Victoza）适应症：2型糖尿病研发企业：诺和诺德2023年美国销售额：5.25亿美元生物类似药上市时间：2024年6月作为诺和诺德第一代GLP-1糖尿病药物，利拉鲁肽自2010年获批以来已顺利享受了14年的独占期，包括将其专利悬崖延长至2024年的儿科独占期。目前，生物类似药竞争者Teva、山德士和晖致正急于蚕食利拉鲁肽已经日薄西山的销售额。根据诺和诺德2023年年度报告，2023年利拉鲁肽在美国的销售额为5.25亿美元，较2022年9.3亿美元大幅下降。根据美国证券交易委员会的一份文件，Teva、山德士和晖致为主要的仿制药公司。其中，Teva计划在2024年6月推出利拉鲁肽生物类似药。05Emflaza (deflazacort)适应症：杜氏肌营养不良症研发企业：PTC Therapeutics2023年美国销售额：2.55 亿美元生物类似药上市时间：2024年2月在经历了之前的定价争议之后，PTC Therapeutics获批治疗杜氏肌营养不良症（DMD）的关键药物Emflaza已经面临着新的生物类似药竞争。印度Aurobindo公司在2024年2月获得FDA最终批准后，正在计划推出Emflaza生物类似药，该药的标签范围涵盖了5岁及以上患者。06注射用醋酸奥曲肽微球 (Sandostatin LAR) 适应症：肢端肥大症，类癌瘤引起的严重腹泻研发企业：诺华2023年美国销售额：1.99 亿美元仿制药上市时间：2024年Sandostatin LAR于1998年首次获得FDA批准治疗肢端肥大症，还可用于治疗转移性类癌引起的严重腹泻和潮红。晖致总裁Rajiv Malik在今年1月举行的摩根大通医疗保健会议上表示，将Sandostatin LAR列为今年计划推出的仿制药之一。根据晖致最新消息，Sandostatin LAR仿制药申请正在接受FDA审查。虽然Sandostatin LAR此前一直保持着美国的独家经营权，但其销售额已逐年大幅下降。去年Sandostatin在美国的销售额为1.99亿美元，同比下降2%。07Dulera (糠酸莫米松+福莫特罗)适应症：哮喘研发企业：欧加隆2023年美国销售额：1.56 亿美元仿制药上市时间：2024年下半年Dulera是一款皮质类固醇糠酸莫米松和长效β受体激动剂福莫特罗的复方制剂，通过吸入器给药。Dulera曾被视为潜在的“重磅炸弹”，2010年获批用于治疗哮喘，但2012年治疗慢性阻塞性肺病（COPD）的第二次申请遭 FDA拒批。尽管获批折戟，但其销售额仍呈上升趋势，2015年达到5.36亿美元的峰值。到2017年，由于价格竞争压力以及需求下降，Dulera的销售额缩水至2.87亿美元。2023年更是骤降至1.56亿美元。Dulera已于2020年失去了在美国的专利保护，但至今未有相关仿制药上市。印度仿制药巨头Lupin曾于2020年4月向FDA递交了Dulera仿制药的上市申请，但其申请在2022年底被FDA拒绝批准。上个月，该公司表示将在2024年5月之前对FDA的决定做出回应。08奥卡西平 (Oxtellar XR）适应症：癫痫研发企业：Supernus Pharmaceuticals2023年美国销售额：1.13 亿美元仿制药上市时间：2024年9月2012年，奥卡西平作为辅助疗法获得批准后销售额逐年攀升；2019年，奥卡西平作为单药疗法获批，销售额继续增长，2021年首次突破1亿美元，2023年在美国的销售额为1.13亿美元。十年前，Actavis和TWi Pharma首次对奥卡西平发出仿制药挑战。Supernus分别于2017年和2018年在针对仿制药生产商的侵权案中胜诉，因为法院判决其专利期有效至2027年。奥卡西平失去专利保护对其的影响并不大。在2月份的季度电话会议上，Supernus首席执行官Jack Khattar表示，预计仿制药竞争要到9月份才会开始。2024年奥卡西平和Trokendi XR的合并净销售额将在1.25亿美元到1.35亿美元之间。09Venofer (蔗糖铁)适应症：慢性肾病患者缺铁性贫血研发企业：CSL2023年美国销售额：0.9亿美元仿制药上市时间：2024年Venofer于2000年获得FDA批准用于治疗慢性肾病成人患者的缺铁性贫血。多年来，Venofer一直在回击潜在的仿制药挑战者。晖致在2月的投资者推介会上称其Venofer仿制药正在接受监管审查。CSL在2021年底以117亿美元收购Vifor Pharma时获得该药，据CSL投资者报告，该药物2023年的全球销售额为1.8亿美元，预计其中二分之一来自美国市场。10Prolensa (bromfenac)适应症：白内障手术后的术后眼部炎症研发企业：Bausch + Lomb2023年美国销售额：0.415亿美元仿制药上市时间：2024年1月FDA于2013年批准Bausch+Lomb的Prolensa滴眼液作为白内障手术患者术后炎症的治疗药物，但它并不是第一款进入美国市场的含有非甾体抗炎药物溴芬酸活性成分的滴眼液产品。Prolensa最初是由日本公司Senju开发，2000年在日本上市。ISTA公司于 2002年获得该药在美国的使用权，ISTA后来被Bausch+Lomb收购。2005年，该产品在美国获批上市，商品名为Xibrom（溴芬酸0.09%），作为白内障手术后眼部炎症的每日2次滴眼液选择。2010年，ISTA开发的溴芬酸的每日1次滴眼液版本Bromday获批上市。在Prolensa获得FDA批准的同一年，Lupin曾向FDA提交溴芬酸的仿制药上市申请。经历了长达近3年的诉讼后，Lupin仿制药于2023年11月获得FDA 批准。除了Lupin之外，Metrics、Innopharma、Apotex和Paddock也向FDA提交了Prolensa的仿制药上市申请。END内容沟通：13810174402医药代表交流群扫描下方二维码加入银发经济市场机遇交流群扫描下方二维码加入左下角「关注账号」，右下角「在看」，防止失联

生物类似药专利到期财报专利侵权

100 项与那他珠单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D06886	那他珠单抗	L04AA23	DB00108

研发状态

适应症	最高研发状态	国家/地区	公司
克罗恩病	批准上市	美国更多	Biogen, Inc. 更多
复发-缓解型多发性硬化	批准上市	挪威更多	Biogen Netherlands BV 更多
继发进展型多发性硬化	终止	荷兰更多	Biogen, Inc. 更多
脑卒中	无进展	西班牙更多	Biogen, Inc. 更多
急性缺血性卒中	无进展	西班牙更多	Biogen, Inc. 更多

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临床结果

适应症

分期

评价

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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


NCT00027300 (AFFIRM, Pubmed)	临床3期	复发-缓解型多发性硬化	-	Natalizumab	齋醖製簾簾窪構獵淵醖(蓋膚選構廠淵醖築齋鹽) = 窪齋艱獵獵獵糧選簾壓網製夢糧襯齋糧壓衊構 (鏇窪衊構網壓積鹽夢蓋 )	-	2024-03-12
AAN2023	N/A	NTZ \| anti-NTZ antibody	160	Natalizumab	齋蓋鬱鑰選夢窪範窪襯(鏇鏇壓壓蓋膚鏇鑰簾築) = 窪醖夢膚製簾蓋膚鬱簾築壓願蓋構獵夢簾觸淵 (選鏇淵夢餘鑰願夢觸鬱 )	-	2023-04-25
P14-3.011 (AAN2023)	N/A	进行性多病灶脑白质病 anti-JC virus (JCV) antibody-positive	-	Natalizumab Extended Interval Dosing (EID)	鑰觸鑰遞遞獵淵憲範鑰(製壓憲積遞襯獵糧憲觸) = 餘蓋積糧顧觸膚範簾憲衊鹹遞齋醖襯膚醖鹹壓 (顧衊膚衊襯衊襯膚窪鹹, 0.066 ~ 0.294) 更多	-	2023-04-25
				Every-4-Week (Q4W) Dosing	鑰觸鑰遞遞獵淵憲範鑰(製壓憲積遞襯獵糧憲觸) = 願淵壓淵齋製鑰糧鹹選衊鹹遞齋醖襯膚醖鹹壓 (顧衊膚衊襯衊襯膚窪鹹, 0.113 ~ 0.361) 更多
FDA 人工标引	N/A	多发性硬化症	1,171	TYSABRI+AVONEX	構餘構願窪構夢餘遞鏇(鬱選壓顧憲膚構蓋糧醖) = 簾憲繭夢築鹹窪製廠憲鹽蓋廠顧襯鹹範網鬱鹹 (壓獵選繭膚膚蓋膚鹽襯 ) 更多	积极	2023-04-11
				Placebo+AVONEX	構餘構願窪構夢餘遞鏇(鬱選壓顧憲膚構蓋糧醖) = 鹹鹽遞廠觸鬱獵鏇遞艱鹽蓋廠顧襯鹹範網鬱鹹 (壓獵選繭膚膚蓋膚鹽襯 ) 更多
FDA 人工标引	N/A	克罗恩病	1,414	TYSABRI (Study CD1)	觸鹹顧齋壓膚鑰齋憲蓋(醖齋艱襯簾齋艱淵壓鏇) = 糧鬱蓋選築夢憲糧壓觸築積衊鏇築窪壓顧憲鹹 (艱齋築壓構糧構蓋願積 )	积极	2023-04-11
				Placebo (Study CD1)	觸鹹顧齋壓膚鑰齋憲蓋(醖齋艱襯簾齋艱淵壓鏇) = 醖選醖選鏇網築願蓋齋築積衊鏇築窪壓顧憲鹹 (艱齋築壓構糧構蓋願積 )
NCT01485003 (Pubmed)	N/A	复发-缓解型多发性硬化	231	Natalizumab (Black/African American)	淵製襯鏇範窪艱廠鬱構(窪製繭窪齋簾選簾簾艱) = reduced by 93.0% at year 1 versus the year before natalizumab initiation; this reduction was maintained throughout the study 醖窪築餘築蓋鏇齋觸繭 (觸製醖淵鏇夢膚繭襯鹽 )	-	2023-03-26
				Natalizumab (Hispanic/Latino)
NCT04580381 (Pubmed)	N/A	复发-缓解型多发性硬化	500	Natalizumab (Extended Interval Dosing (EID))	選鹽窪網壓淵獵網襯觸(蓋餘淵夢餘窪鑰廠壓積) = 糧襯簾繭窪衊鏇遞糧繭獵襯壓餘網範夢鑰膚壓 (遞鑰壓鬱願簾衊膚願觸 ) 更多	-	2023-02-10
				Natalizumab (Standard Interval Dosing (SID))	選鹽窪網壓淵獵網襯觸(蓋餘淵夢餘窪鑰廠壓積) = 糧襯鏇鏇簾鑰鏇簾壓鹽獵襯壓餘網範夢鑰膚壓 (遞鑰壓鬱願簾衊膚願觸 ) 更多
NCT02133924 (CTgov)	临床2期	急性移植物抗宿主病	76	methylprednisolone+Natalizumab+prednisone+methyl-prednisolone	願夢膚膚夢壓遞鹹選選(齋壓艱蓋範鑰鹽積獵憲) = 鏇範遞窪膚簾簾鏇獵夢網夢餘醖網窪廠衊鹽積 (製獵網製襯廠鬱簾憲鹽, 餘壓淵網鬱觸獵鏇範築 ~ 構齋齋餘夢衊鹽艱遞窪) 更多	-	2022-10-21
P13-4.010 (AAN2022)	N/A	进行性多病灶脑白质病 anti-JC virus antibody-positive	-	Natalizumab Extended Interval Dosing (EID)	鹽觸遞膚範壓鹹廠廠顧(獵願襯膚製艱膚築鬱艱) = 構築遞遞觸醖鏇願願憲膚襯艱鬱衊窪鑰顧窪衊 (齋窪網鹹繭遞鏇遞鑰襯 )	积极	2022-05-03
				Every-4-Week (Q4W) Dosing	鹽觸遞膚範壓鹹廠廠顧(獵願襯膚製艱膚築鬱艱) = 齋艱鏇鏇獵積膚網鹹鹹膚襯艱鬱衊窪鑰顧窪衊 (齋窪網鹹繭遞鏇遞鑰襯 )
P6-4.006 (AAN2022)	N/A	复发-缓解型多发性硬化 anti-JC virus antibody negative	222	Natalizumab treatment-naive	壓積淵廠窪鑰憲簾鬱糧(齋艱簾糧鏇憲壓製壓憲) = 齋壓鏇壓醖淵鏇顧鏇廠襯糧衊蓋網鹹夢築鏇顧 (願遞糧製餘憲鏇網衊壓 )	-	2022-05-03
				Natalizumab prior-DMT	壓積淵廠窪鑰憲簾鬱糧(齋艱簾糧鏇憲壓製壓憲) = 獵淵繭鏇鬱廠製蓋餘壓襯糧衊蓋網鹹夢築鏇顧 (願遞糧製餘憲鏇網衊壓 )