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.

Start Date01 Jun 2024

Sponsor / Collaborator

The Case Comprehensive Cancer Center

NCT05658497 / RecruitingNot Applicable

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).

Start Date27 Oct 2023

Sponsor / Collaborator

Biogen, Inc.

NCT05618301 / RecruitingPhase 1IIT

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.

Start Date07 Jul 2023

Sponsor / Collaborator

Washington University School of Medicine

[+2]

100 Clinical Results associated with Natalizumab

100 Translational Medicine associated with Natalizumab

100 Patents (Medical) associated with Natalizumab

2,833

Literatures (Medical) associated with Natalizumab

31 Dec 2024·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

Author: Karabudak, R ; Girard, M ; Horakova, D ; Hodgkinson, S ; Castillo-Triviño ; Gerlach, O ; Gray, O ; Cartechini, E ; de Gans, K ; McCombe, P ; Spitaleri, D ; Solaro, C ; Sas, A ; Garber, J ; 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 ; Butzkueven, H ; Herring, W L ; 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.

13 Feb 2024·Neurology

Adverse Events Associated With Disease-Modifying Drugs for Multiple Sclerosis

Article

Author: Fisk, John D ; Zhu, Feng ; Ekuma, Okechukwu ; Yao, Shenzhen ; Marrie, Ruth Ann ; Ng, Huah Shin ; Lu, Xinya ; Zhao, Yinshan ; 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.

01 Feb 2024·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

Author: 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.

117

News (Medical) associated with Natalizumab

17 Jun 2024

·www.fiercebiotech.com

Siemens Healthineers nets European approval for blood test to predict MS relapse risks

Elevated levels of neurofilament light chain are also being studied across a range of neurological conditions, where damaged nerve cells serve as a hallmark of the disease, such as dementia, Alzheimer's and ALS. Siemens Healthineers received European approval for a blood test designed to help predict the risk of recurrence among patients with relapsing multiple sclerosis. The company’s CE-marked in vitro diagnostic measures the amount of neurofilament light chain proteins found in serum and plasma, which are released into the bloodstream when the brain’s neurons are under siege. When combined with MRI brain scans and other clinical lab tests, it aims to predict which adult patients may have a higher or lower risk of MS disease activity within the following two years. “Neurofilament light chain, or NfL, has emerged as a leading biomarker of nerve cell damage,” Siemens Healthineers’ head of diagnostics R&D, Dennis Gilbert, said in a statement. “Having access to a test that measures this protein capable of crossing the blood-brain barrier to support earlier prognostication of disease activity would be a critical scientific advancement for MS patients.” The test—run on the company’s Atellica IM and the ADVIA Centaur analyzers—is the result of a years-long collaboration with Novartis, which launched in 2020 shortly after the drugmaker received an FDA approval for its Kesimpta therapy for relapsing-remitting and secondary progressive MS. Novartis would also go on to collect the first U.S. green light for a biosimilar MS drug, with its version of Biogen’s blockbuster Tysabri. “While there is no cure for MS, treatments exist to decrease the frequency of relapses, thought to be associated with nerve cell damage and disease progression,” Gilbert said. “What patients still need is an easily accessible, cost-effective, and accurate blood-based test that would indicate early signs of neuronal injury and disease activity.” Elevated levels of neurofilament light chain, in both the blood and cerebrospinal fluid, are also being studied across a range of neurological conditions where damaged nerve cells serve as a hallmark of the disease—such as dementia and amyotrophic lateral sclerosis, the motor neuron disease commonly known as ALS. Meanwhile, NfL was incorporated into Labcorp’s blood test aimed at Alzheimer’s disease last fall, alongside measurements of hallmark amyloid and tau proteins.

28 May 2024

·www.prnewswire.com

BioLineRx Reports First Quarter 2024 Financial Results and Recent Corporate and Portfolio Updates

- Steady growth in APHEXDA® adoption in first full quarter post-approval - - Among top 80 transplant centers, secured APHEXDA formulary placement to date at institutions representing ~26% of stem cell transplant procedures performed - on track to reach stated goal of ~35% by end of Q2 - - Announced new data in abstract accepted at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting on pilot phase of ongoing Phase 2b pancreatic cancer clinical trial collaboration with Columbia University - - Collaboration partner Gloria Biosciences' motixafortide HSC mobilization bridging study IND was filed and approved by the Center for Drug Evaluation of the National Medical Products Administration in China. Anticipate clinical trial initiation 2H 2024 - - Completed debt and equity financing totaling $26 million to support U.S. commercialization of APHEXDA and advance lifecycle expansion activities - - Management to host conference call today, May 28, at 8:30 am EDT - TEL AVIV, Israel, May 28, 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 unaudited financial results for the first quarter ended March 31, 2024, and provided recent corporate and portfolio updates. "In this first full quarter post APHEXDA® approval, we were pleased by the steady growth in adoption and repeat purchases by transplant centers, which is consistent with our expectations during this foundational period," said Philip Serlin, Chief Executive Officer of BioLineRx. "This growth comes as we see continued increases in the number of transplant centers that have completed Pharmacy & Therapeutics committee reviews and granted approval for APHEXDA usage. As a reminder, end users of APHEXDA are well defined, with 80 of the 212 U.S. transplant centers performing approximately 85% of all transplant procedures. Importantly, among these top 80 transplant centers, we've secured formulary placement to date at institutions representing ~26% of stem cell transplant procedures performed, keeping us on track to reach our stated goal of 35% by the end of Q2. "In our major pipeline program in pancreatic cancer, we continue to see strong data emerge from the pilot phase of the Phase 2 PDAC trial sponsored by Columbia University. Last week we announced new data in an accepted ASCO abstract on paired pre- and on-treatment biopsy data that show a significant increase in CD8+ T-cell density in tumors from all 11 patients treated—further reinforcing our belief in the potential of the combination of motixafortide with a PD-1 inhibitor to treat this very challenging cancer with substantial unmet need. "Finally, we are also making great progress pursuing motixafortide's potential to support gene therapy for patients with sickle cell disease, which requires significant quantities of hematopoietic stem cells. This is an important growth program, and we are actively working with a number of leaders in the gene therapy field, while looking forward to the second half of this year when early data from our collaboration with Washington University in St. Louis is expected." Corporate Updates Accessed $20 million in non-dilutive debt financing from previously announced agreement with BlackRock EMEA Venture and Growth Lending (previously Kreos Capital) and completed a $6 million registered direct equity offering. Funds will be used to support ongoing commercialization of APHEXDA in the U.S. and to advance lifecycle expansion activities 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 protections offered by 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 Among top 80 transplant centers, secured formulary placement to date at institutions representing ~26% of stem cell transplant procedures performed – on track to reach stated goal of ~35% by end of Q2 and ~60% by year-end 2024 Granted "pass through" status from the Centers for Medicare and Medicaid Services (CMS), ensuring that reimbursement for APHEXDA for Medicare and certain commercial payers will be separate from payment bundling methodologies when administered in the hospital outpatient setting Clinical Portfolio Updates Motixafortide (selective inhibitor of CXCR4 chemokine receptor) Multiple Myeloma Presented posters at both the American Society for Apheresis 2024 Annual Meeting on April 17, 2024, and the International Society for Pharmacoeconomics and Outcomes Research on April 6, 2024. The posters reviewed apheresis center efficiency between CXCR4 antagonists, including APHEXDA, in patients with multiple myeloma, as well as economic model data on APHEXDA for HSC mobilization in patients with multiple myeloma Collaboration partner Gloria Biosciences' stem cell mobilization bridging study IND filed and approved by the Center for Drug Evaluation of the National Medical Products Administration in China. Anticipate initiation of pivotal clinical trial in 2H 2024 Pancreatic Ductal Adenocarcinoma (mPDAC) Announced new data in an abstract accepted at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting on the pilot phase of the ongoing CheMo4METPANC Phase 2 clinical trial collaboration with Columbia University, including new analysis of paired pre- and on-treatment biopsy samples. The presentation will be held on June 1, 2024 in Chicago, IL Announced first patient dosed in the randomized CheMo4METPANC Phase 2 clinical trial, an expansion of the pilot phase single-arm study, evaluating motixafortide in combination with the PD-1 inhibitor cemiplimab and standard-of-care chemotherapy as first-line treatment in 108 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 initial data in 2H 2024 First Quarter 2024 Financial Results Total revenue for the first three months ended March 31, 2024 was $6.9 million. The Company did not record any revenue during the first quarter of 2023. Revenue for the quarter reflect a portion of the upfront payment from the Gloria Biosciences license agreement and a milestone payment achieved under the same license agreement, which collectively amounted to $5.9 million, as well as $0.9 million of net revenue from product sales of APHEXDA in the U.S. Cost of revenue for the first three months ended March 31, 2024 was $1.5 million. The Company did not record any cost of revenue during the first quarter of 2023. The cost of revenue for the quarter primarily reflects sub-license fees on a milestone payment received under the Gloria Biosciences license agreement and royalties on net product sales of APHEXDA in the U.S., as well as amortization of intangible assets and cost of goods sold on product sales Research and development expenses for the first three months ended March 31, 2024 were $2.5 million, compared to $3.7 million for the same period in 2023. The decrease resulted primarily from lower expenses related to motixafortide New Drug Application (NDA) supporting activities, as well as termination of the development of AGI-134 Sales and marketing expenses for the first three months ended March 31, 2024 were $6.3 million, compared to $3.9 million for the same period in 2023. The increase resulted primarily from the ramp-up of commercialization activities related to motixafortide, including headcount costs associated with fully hired field team General and administrative expenses for the first three months ended March 31, 2024 were $1.4 million, compared to $1.3 million for the same period in 2023. The increase resulted primarily from a small increase in share-based compensation Non-operating income for the first three months ended March 31, 2024 was $4.5 million, compared to non-operating expenses of $2.9 million for the same period in 2023. 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 first three months ended March 31, 2024 was $0.7 million, compared to $12.2 million for the same period in 2023. The net loss for the 2024 period included $4.5 million in non-cash income, compared to non-operating expenses of $2.9 million for the same period in 2023, both specifically related to the revaluation of warrants As of March 31, 2024, the Company had cash, cash equivalents, and short-term bank deposits of $28.2 million. This amount does not include $6.0 million in gross proceeds received from a registered direct offering and a $20.0 million drawdown of the second tranche from the existing loan agreement with BlackRock, which were both completed in April 2024. The Company anticipates that this amount will be sufficient to fund operations, as currently planned, into 2025 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 May 30, 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 [email protected] Israel Moran Meir LifeSci Advisors, LLC [email protected] Logo - SOURCE BioLineRx Ltd.

License out/inOrphan DrugPhase 2Drug Approval

07 May 2024

·www.globenewswire.com

Sandoz reports first quarter 2024 sales

Ad hoc announcement pursuant to art. 53 SIX Swiss Exchange Listing Rules MEDIA RELEASE Strong first quarter performance, with net sales [1] of USD 2.5 billion, up 6% in constant currencies (up 5% in USD)Biosimilar business growing 21% in constant currencies All regions contributing to growthAcquisition of CIMERLI® (ranibizumab-eqrn) completed in March 2024 Basel, May 7, 2024 – Sandoz (SIX:SDZ/OTCQX:SDZNY), the global leader in generic and biosimilar medicines, today announced net sales for the first quarter 2024. Net sales were USD 2.5 billion, an increase of 6% in constant currencies compared to the same quarter of the prior year. Biosimilars saw another quarter of double-digit net sales growth, an increase of 21% in constant currencies. Generics sales remained in line with prior year levels. Richard Saynor, Chief Executive Officer of Sandoz, said: “We saw a strong start to the year as we report our 10th consecutive quarter of topline growth. The momentum in our business continues as demonstrated by double-digit growth in biosimilars and a positive contribution by all regions.” Mr. Saynor continued: “Biosimilars are a key element of performance, driven by strong results in our existing portfolio, demand for our recently launched product Hyrimoz® (adalimumab-adaz) in the US and the recent acquisition of CIMERLI® (ranibizumab-eqrn), which closed in early March. Generics remained in line with the strong prior year sales. Looking forward, we are confident in our ability to continue to grow our top line and meet our full-year net sales guidance of mid-single digits in constant currencies.” FIRST QUARTER NET SALES RESULTSNet sales for the first quarter were USD 2.5 billion, up 6% in constant currencies, compared to the first quarter of 2023. Volume contributed 10 percentage points of growth, partially offset by price erosion of 4 percentage points. Biosimilars were a key driver of growth in the quarter, while generics remained in line with the strong prior year sales. Net sales by business Three months ended March 31 Change % USD millions unless indicated otherwise 2024 2023 USD cc* Generics 1869 1868 0 1 Biosimilars 623 516 21 21 Net sales to third parties 2492 2384 5 6 *Constant currencies Generics overviewNet sales for the first quarter were USD 1.9 billion, up 1% in constant currencies, compared to the first quarter of 2023. Solid volume demand was partly offset by the impact from the withdrawal of apixaban in the Netherlands following a court decision in August 2023, an exceptional cough and cold season in the first half of 2023 and the timing of new launches in the US. Biosimilars overviewNet sales for the first quarter were USD 623 million, up 21% in constant currencies, compared to the first quarter of 2023. This strong double-digit biosimilar growth reflects the ongoing launch of Hyrimoz® high-concentration formulation, the acquisition of CIMERLI® as well as continued strong demand for our first-ever biosimilar, Omnitrope®. Net sales by region Three months ended March 31 Change % USD millions unless indicated otherwise 2024 2023 USD cc Europe 1326 1270 4 2 North America 524 496 6 6 International 642 618 4 12 Net sales to third parties 2492 2384 5 6 Europe overviewNet sales for the first quarter were USD 1.3 billion, up 2% in constant currencies, compared to the first quarter of 2023. Generic volume growth remained positive despite a strong prior year comparison from peak sales of apixaban and an exceptional cough and cold season. Biosimilars showed strong sales growth, led by demand for Omnitrope® and contribution from the recent launch of Tyruko® (natalizumab) in several key countries. North America overviewNet sales for the first quarter were USD 524 million, up 6% in constant currencies, compared to the first quarter of 2023. Growth was driven by the ongoing launch of Hyrimoz® in the US, continued demand for Omnitrope®, the acquisition of CIMERLI® which closed in early March, and the transfer of mature brands from our former parent in the fourth quarter of 2023. This was partly offset by a decline in generics sales due to the timing of new launches in the US. International overviewNet sales for the first quarter were USD 642 million, up 12% in constant currencies, compared to the first quarter of 2023. This was primarily a result of strong volume growth across both generics and biosimilars, the acquisition of Mycamine® in the prior year and favorable price dynamics. GUIDANCE 2024The company reiterates its full-year 2024 guidance, expecting net sales to grow mid-single digit in constant currencies versus prior year and core EBITDA margin around 20%. FIRST QUARTER STRATEGIC MILESTONESOn January 31, we announced the launch of Tyruko® in Germany. Developed by Polpharma Biologics, Tyruko® is the first and only biosimilar to treat relapsing remitting multiple sclerosis. The availability of Tyruko® is a crucial milestone in improving access to effective and safe therapies for those in Europe that need them most. On March 4, we announced the completion of the US biosimilar CIMERLI® acquisition from Coherus BioSciences, Inc, ahead of anticipated timelines. The acquisition builds on the leading Sandoz ophthalmic platform in the US and lays an even stronger foundation for future product launches. On March 5, we announced that Remco Steenbergen, currently a Sandoz Board member, will become a member of the Executive Committee and take on the responsibility of Sandoz CFO as of July 1, 2024. Remco will succeed Colin Bond who will step down from his position as of June 30, 2024, and retire in January 2025 per Swiss employment practice. Colin will be available for transition as a senior advisor through the end of 2024. On March 5, we also announced that the US Food and Drug Administration (FDA) approved Wyost® (denosumab-bbdz) and Jubbonti® (denosumab-bbdz), the first and only FDA-approved denosumab biosimilars, to treat all indications of the reference medicines including osteoporosis and cancer-related skeletal events. KEY LINKSWebcast – Live at 9am CETAnalyst Call PresentationAnalyst Consensus NON-IFRS MEASURES IN THIS DOCUMENT AS DEFINED BY SANDOZSandoz uses certain non-IFRS metrics when measuring performance, especially when measuring current period results against prior periods, including core results, constant currencies and free cash flow. Despite the use of these measures by management in setting goals and measuring Sandoz performance, these are non-IFRS measures that have no standardized meaning prescribed by IFRS Accounting Standards. As a result, such measures have limits in their usefulness to investors. Because of their non-standardized definitions, the non-IFRS measures (unlike IFRS measures) may not be comparable to the calculation of similar measures of other companies. These non-IFRS measures are presented solely to permit investors to more fully understand how Sandoz management assesses underlying performance. These non-IFRS measures are not, and should not be viewed as, a substitute for IFRS measures, and should be viewed in conjunction with IFRS financials. As an internal measure of Group performance, these non-IFRS measures have limitations, and Sandoz performance management process is not solely restricted to these metrics. The definitions of the non-IFRS financial metrics as used by Sandoz are as follows: Core resultsSandoz core results – including core EBITDA, core operating income, core net income and core earnings per share – exclude fully: The amortization and impairment charges of intangible assets other than software;Net gains and losses on fund investments and equity securities valued at fair value through profit and loss;Certain acquisition and divestment- related items;Tax liabilities for uncertain tax positions. The following items that exceed a threshold of USD 25 million are also excluded: Integration- and divestment- related income and expenses;Divestment gains and losses;Restructuring charges/releases and related items;Legal related items;Impairments of property, plant and equipment, software and financial assets;And income and expense items that management deems exceptional and that are or are expected to accumulate within the year to be over a USD 25 million threshold. Income tax impacts of such items are also excluded from core measures. Sandoz believes that investor understanding of its performance is enhanced by disclosing core measures of performance because, since core measures exclude items that can vary significantly from year to year, they enable a better comparison of business performance across years. For this same reason, Sandoz uses these core measures in addition to IFRS and other measures as important factors in assessing its performance. The following are examples of how these core measures are utilized: In addition to monthly reports containing financial information prepared under IFRS, senior management receives a monthly analysis incorporating these core measures;Annual budgets are prepared for both IFRS and core measures. As an internal measure of Sandoz performance, the core results measures have limitations, and the Sandoz performance management process is not solely restricted to these metrics. A limitation of the core results measures is that they provide a view of the Sandoz operations without including all events during a period, such as the effects of an acquisition, divestment, or amortization/impairments of purchased intangible assets, impairments to property, plant and equipment and restructurings and related items. Constant currenciesChanges in the relative values of non-US currencies to the US dollar can affect Sandoz financial results and financial position. To provide additional information that may be useful to investors, including changes in sales volume, Sandoz presents information about its net sales and various values relating to operating and net income that are adjusted for such foreign currency effects. Constant currency calculations have the goal of eliminating two exchange rate effects so that an estimate can be made of underlying changes in the consolidated income statement excluding the impact of fluctuations in exchanges rates: The impact of translating the income statements of consolidated entities from their non-USD functional currencies to USD;The impact of exchange rate movements on the major transactions of consolidated entities performed in currencies other than their functional currency. Sandoz calculates constant currency measures by translating the current year’s foreign currency values for sales and other income statement items into USD (excluding the IAS 29 “Financial Reporting in Hyperinflationary Economies” adjustments to the local currency income statements of subsidiaries operating in hyperinflationary economies), using the average exchange rates from the prior year and comparing them to the prior year values in USD. Sandoz uses these constant currency measures in evaluating its performance, since they may assist the Group in evaluating its ongoing performance from year to year. However, in performing its evaluation, Sandoz also considers equivalent measures of performance that are not affected by changes in the relative value of currencies. EBITDASandoz defines earnings before interest, tax, depreciation, and amortization (EBITDA) as operating income, excluding depreciation of property, plant and equipment and right-of-use assets, amortization of intangible assets, impairments of property, plant and equipment, right-of-use assets, and intangible assets. Core EBITDA marginSandoz defines core EBITDA margin as the percentage of core EBITDA over net sales to third parties. It is an indicator to measure the profitability of the Group. CurrenciesReferences to “USD” or “U.S. dollars” are to the lawful currency of the United States of America. RoundingCertain figures contained in the media release, including financial information presented in millions or thousands, certain operating data and percentages describing financial information or market shares, have been subject to rounding. Accordingly, in certain instances, the amounts shown as totals in tables or elsewhere may not conform exactly to the arithmetic total of the figures that precede them. In addition, certain percentages reflect calculations based upon the underlying information prior to rounding and, accordingly, may not conform exactly to the percentages that would be derived if the relevant calculations were based upon the rounded numbers. DISCLAIMERThis Media Release contains forward-looking statements, which offer no guarantee with regard to future performance. These statements are made on the basis of management’s views and assumptions regarding future events and business performance at the time the statements are made. They are subject to risks and uncertainties including, but not confined to, future global economic conditions, exchange rates, legal provisions, market conditions, activities by competitors and other factors outside of the control of Sandoz. Should one or more of these risks or uncertainties materialize or should underlying assumptions prove incorrect, actual outcomes may vary materially from those forecasted or expected. Each forward-looking statement speaks only as of the date of the particular statement, and Sandoz undertakes no obligation to publicly update or revise any forward-looking statements, except as required by law. ABOUT SANDOZSandoz (SIX: SDZ; OTCQX: SDZNY) is the global leader in generic and biosimilar medicines, with a growth strategy driven by its Purpose: pioneering access for patients. More than 20,000 people of more than 100 nationalities work together to ensure 800 million patient treatments are provided annually by Sandoz, generating substantial global healthcare savings and an even larger social impact. Its leading portfolio of approximately 1500 products addresses diseases from the common cold to cancer. Headquartered in Basel, Switzerland, Sandoz traces its heritage back to 1886. Its history of breakthroughs includes Calcium Sandoz in 1929, the world’s first oral penicillin in 1951, and the first biosimilar in 2006. CONTACTS Global Media Relations contacts Investor Relations contacts Global.MediaRelations@sandoz.com Investor.Relations@sandoz.com Joerg E. Allgaeuer+49 171 838 4838 Karen M. King+1 609 722 0982 Chris Lewis+49 174 244 9501 Laurent de Weck+41 61 529 14 85 SUPPORTING FINANCIAL INFORMATION Quarterly sales Q1 2024 USD millions unless indicated otherwise Q1 2024 Change % USD cc Generics 1869 0 1 Biosimilars 623 21 21 Net sales to third parties 2492 5 6 Europe 1326 4 2 North America 524 6 6 International 642 4 12 Net sales to third parties 2492 5 6 FY 2023 USD millions unless indicated otherwise Q1 2023 Change % Q2 2023 Change % Q3 2023 Change % Q4 2023 Change % USD cc USD cc USD cc USD cc Generics 1868 2 6 1850 4 6 1794 5 4 1920 6 6 Biosimilars 516 11 17 533 13 14 543 7 4 623 29 26 Net sales to third parties 2384 4 9 2383 5 8 2337 6 4 2543 11 10 Europe 1270 10 16 1277 14 12 1204 11 3 1272 10 4 North America 496 (5) (3) 508 (4) (2) 510 (4) (3) 615 20 20 International 618 (1) 4 598 (3) 8 623 3 12 656 4 14 Net sales to third parties 2384 4 9 2383 5 8 2337 6 4 2543 11 10 [ 1 ] Net sales in this document refer systematically to net sales to third parties. Attachment SANDOZ Q1 Sales Media Release

Executive ChangeAcquisitionDrug ApprovalBiosimilar

100 Deals associated with Natalizumab

External Link

KEGG	Wiki	ATC	Drug Bank
D06886	Natalizumab	L04AA23	DB00108

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Crohn Disease	US	Biogen, Inc.	14 Jan 2008
Multiple Sclerosis, Relapsing-Remitting	EU	Biogen Netherlands BV	27 Jun 2006
Multiple Sclerosis, Relapsing-Remitting	IS	Biogen Netherlands BV	27 Jun 2006
Multiple Sclerosis, Relapsing-Remitting	LI	Biogen Netherlands BV	27 Jun 2006
Multiple Sclerosis, Relapsing-Remitting	NO	Biogen Netherlands BV	27 Jun 2006
Multiple Sclerosis	US	Biogen, Inc.	23 Nov 2004

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Multiple Sclerosis, Secondary Progressive	Phase 3	US	Biogen, Inc.	13 Sep 2011
Multiple Sclerosis, Secondary Progressive	Phase 3	BE	Biogen, Inc.	13 Sep 2011
Multiple Sclerosis, Secondary Progressive	Phase 3	CA	Biogen, Inc.	13 Sep 2011
Multiple Sclerosis, Secondary Progressive	Phase 3	CZ	Biogen, Inc.	13 Sep 2011
Multiple Sclerosis, Secondary Progressive	Phase 3	DK	Biogen, Inc.	13 Sep 2011
Multiple Sclerosis, Secondary Progressive	Phase 3	FI	Biogen, Inc.	13 Sep 2011
Multiple Sclerosis, Secondary Progressive	Phase 3	FR	Biogen, Inc.	13 Sep 2011
Multiple Sclerosis, Secondary Progressive	Phase 3	DE	Biogen, Inc.	13 Sep 2011
Multiple Sclerosis, Secondary Progressive	Phase 3	IE	Biogen, Inc.	13 Sep 2011
Multiple Sclerosis, Secondary Progressive	Phase 3	IL	Biogen, Inc.	13 Sep 2011

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03689972 (NOVA, CTgov)	Phase 3	Multiple Sclerosis, Relapsing-Remitting	585	Natalizumab (Part 1: IV Q4W)	xijjukdnne(tvtdoztuqe) = zbfevrxhao ttrsthoyrp (stgjfddend, cmcdlsvsoq - dtnpqnsvns) View more	-	12 Jun 2024
				Natalizumab (Part 1: IV Q6W)	xijjukdnne(tvtdoztuqe) = whzekjyvjf ttrsthoyrp (stgjfddend, gkjmnguncj - cdgijgblrw) View more
NCT00027300 (AFFIRM, Pubmed)	Phase 3	Multiple Sclerosis, Relapsing-Remitting	-	Natalizumab	gctqamunle(jgolywbgxi) = dprwanvhno koycjqhjjh (tngkkewvlp )	-	12 Mar 2024
ACTRIMS2024	Not Applicable	Multiple sclerosis relapse	69	Natalizumab	hgvqgzqvqb(tikuouwyid) = zlqrwugido dfpijkuzix (xryhbvlqka ) View more	Positive	01 Mar 2024
				Ocrelizumab	hgvqgzqvqb(tikuouwyid) = ergplqgzcz dfpijkuzix (xryhbvlqka ) View more
ACTRIMS2024	Not Applicable	Multiple sclerosis relapse John Cunningham Virus (JCV) serology	-	Extended Interval Dosing (EID) Natalizumab	geknzkwpsy(zioggtfmxv) = dusgajniex mwruazquum (oggjaqmghi ) View more	Positive	29 Feb 2024
				Standard Interval Dosing (SID) Natalizumab	geknzkwpsy(zioggtfmxv) = aqcoynhwzq mwruazquum (oggjaqmghi ) View more
NCT05304520 (SISTER study, Pubmed)	Not Applicable	Multiple Sclerosis, Relapsing-Remitting	262	Subcutaneous natalizumab	cqspfbkplq(kzolzmfjzw) = bodinoerid broomgkfml (blmvourteu )	Positive	01 Jan 2024
				Intravenous natalizumab	cqspfbkplq(kzolzmfjzw) = yvmghmqqap broomgkfml (blmvourteu )
ECTRIMS2023	Not Applicable	Multiple Sclerosis	-	Natalizumab exposure during pregnancy	gfgtufcusm(vkosjbuniy) = exposed boys showed a median of 150 gram lower weight (at birth and at about 1 week and 3/6/12 months of age) than boys in controls, which was not statistically significant zyfhftmucw (qviqnmyqne ) View more	-	30 Sep 2023
				No disease modifying therapy pregnancy exposure
ECTRIMS2023	Not Applicable	Multiple Sclerosis, Relapsing-Remitting	86	Natalizumab IV	nkqcyrvotv(smrfcetibf) = fmzkckoetz bouzvirngr (iqjvcjvfgm ) View more	-	30 Sep 2023
				Natalizumab SC	fzmsentuho(nzcgbhvspv) = exkjfxkpth whooxpkfgp (vviwtljgpp )
ECTRIMS2023	Not Applicable	Leukoencephalopathy, Progressive Multifocal JC virus (JCV)	86	Natalizumab	jolyfcskaw(cgpbumzkdx) = jjstnvnorq rkhztwsqoc (ajlvhumbkc )	Positive	30 Sep 2023
ECTRIMS2023	Not Applicable	Multiple Sclerosis, Relapsing-Remitting	5,972	Natalizumab	tyabkvbigb(dxfchculuu): HR = 0.98 (95% CI, 0.84 - 1.14), P-Value = 0.8	-	30 Sep 2023
				Fingolimod
ECTRIMS2023	Not Applicable	Multiple Sclerosis, Relapsing-Remitting	661	Natalizumab (NTZ)	alnqtdgdof(eqvfqvofyr): HR = 1.75 (95% CI, 0.88 - 3.48), P-Value = 0.11	-	30 Sep 2023
				Ocrelizumab (OCR)

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