European Commission has approved INAQOVI® (oral decitabine and cedazuridine) for the treatment of adults with newly diagnosed acute myeloid leukaemia

LONDON, UK, and PLEASANTON, CA, USA, 19th September 2023 – Otsuka Pharmaceutical Europe Ltd. (Otsuka) and Astex Pharmaceuticals, Inc. (Astex) today announce that the European Commission (EC) has approved INAQOVI® (oral decitabine and cedazuridine) as monotherapy for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for standard induction chemotherapy. The EC decision applies to the European Economic Area (EEA), which includes the EU member states, Iceland, Liechtenstein and Norway. INAQOVI® is the first and only oral hypomethylating agent licensed in the EEA in this patient population.

The EC approval is based on the results from the Phase 3 ASCERTAIN clinical trial investigating the pharmacokinetic exposure equivalence of the novel oral fixed-dose combination versus intravenous (IV) decitabine in AML patients1. The ASCERTAIN study met its primary endpoint, with the orally administered decitabine and cedazuridine fixed-dose combination showing pharmacokinetic exposure equivalence to a standard 5-day regimen of IV decitabine using a two-cycle, cross-over study design. Safety findings for the fixed-dose combination of decitabine and cedazuridine were generally consistent with those anticipated for IV decitabine1.

The current treatment options for adults with AML range from hospital-administered IV chemotherapy infusions or, for those patients not eligible for chemotherapy, regimens based on parenterally administered hypomethylating agents, with treatment cycles typically extending for 5-7 days2. Fatigue can significantly restrict daily activities and impact a patient’s quality of life3. INAQOVI® may provide both patients and physicians with an oral treatment option in this patient population.

On 10th June 2022, the European Medicines Agency (EMA) agreed to a Paediatric Investigation Plan for the oral decitabine and cedazuridine fixed-dose combination, representing an important milestone for the prospect of furthering clinical studies in children with AML.

About decitabine and cedazuridine fixed-dose combination (INAQOVI®)

INAQOVI® is an orally administered, fixed-dose combination of the approved hypomethylating agent (HMA), decitabine (35 mg), together with cedazuridine (100 mg), an inhibitor of cytidine deaminase4-6. By inhibiting cytidine deaminase in the gut and liver, the fixed-dose combination is designed to allow for oral daily administration of decitabine over 5 days in a given cycle to achieve comparable systemic exposure to IV decitabine administered with the same dosing regimen7.

In the Phase 3 ASCERTAIN study, a total of 89 AML patients were randomised 1:1 to receive INAQOVI® (35 mg decitabine and 100 mg cedazuridine) orally in Cycle 1 and decitabine (20 mg/m2) intravenously in Cycle 2 (n=44) or the reverse sequence (n=45). Both INAQOVI® and IV decitabine were administered once daily on Days 1 through 5 of the 28-day cycle. Starting with Cycle 3, all patients received INAQOVI® orally once daily on Days 1 through 5 of each 28-day cycle until disease progression, death, or unacceptable toxicity6.

Primary endpoint results showed that patients receiving INAQOVI® achieved pharmacokinetic exposure equivalence of 99.64% (90% CI: 91.23, 108.8) to IV decitabine given at 20 mg/m2 for 5-days with a similar pharmacodynamic activity. Secondary findings showed a Median Overall Survival of 7.9 months (95% CI: 5.9, 13.0) and a Complete Response rate of 21.8% at 7.95 months median follow up1.

The most common adverse drug reaction (≥ 20%) was thrombocytopenia. The most common serious adverse reactions (≥ 20%) were febrile neutropenia and pneumonia. Permanent discontinuation occurred in 14% of patients while on treatment. The most frequent adverse reaction resulting in permanent discontinuation was pneumonia (5%)6.

 About acute myeloid leukaemia (AML)

AML is the most common form of acute leukaemia in adults8. The median age at diagnosis is approximately 70 years2. Within Europe, the incidence of AML is increasing, this may be attributed to the ageing population; AML incidence in Europe has risen from 3.48 in 1976 to 5.06 patients per 100,000 population in 20132. Across Europe and all age groups, AML is notably more common in males than in females2. The outlook for patients diagnosed with AML has improved over time due to improved care and treatment, however between the years of 2000 and 2007, 5-year survival for patients was just 17%2.

About Otsuka

Otsuka Pharmaceutical is a global healthcare company with the corporate philosophy “Otsuka-people creating new products for better health worldwide”. Otsuka researches, develops, manufactures, and markets innovative products, focusing on pharmaceutical products to meet unmet medical needs and nutraceutical products for the maintenance of everyday health. In pharmaceuticals, Otsuka is a leader in the challenging area of mental health and has research programmes in several under-addressed diseases including tuberculosis, a significant global public health issue.

Otsuka Europe employs around 550 people and focuses on psychiatric and neurologic disorders, infectious disease, nephrology, oncology, and digital medicines.

Otsuka Pharmaceutical Europe Ltd. is a part of Otsuka Pharmaceutical Company, Ltd., a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan.

The Otsuka group of companies employed 47,000 people worldwide with consolidated sales of approximately €12.4 billion and a spend of €1.67 billion on research and development in 2022. For further information on Otsuka, please visit www.otsuka-europe.com.

 About Astex

Astex Pharmaceuticals, Inc. is committed to the fight against cancer. Astex is developing a proprietary pipeline of novel therapies for the treatment of solid tumours and haematological malignancies. Astex is a member of the Otsuka group of companies. The group also includes Otsuka Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Taiho Oncology, Inc. Subject to regulatory approvals, Astex’s products will be commercialised in the U.S. and Canada by Taiho subsidiaries, and in the rest of the world by Otsuka subsidiaries.

TEVIMBRA Receives European Commission Approval for the Treatment of Advanced or Metastatic ESCC

BASEL, Switzerland & BEIJING & CAMBRIDGE, Mass.--(BUSINESS WIRE)--BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company, today announced that the European Commission (EC) has approved TEVIMBRA® (tislelizumab) as monotherapy for the treatment of adult patients with unresectable, locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) after prior platinum-based chemotherapy. Additionally, the U.S. Food and Drug Administration (FDA) accepted for review a Biologics License Application (BLA) for tislelizumab as a first-line treatment for patients with unresectable, recurrent, locally advanced, or metastatic ESCC.

“TEVIMBRA is the cornerstone of BeiGene’s solid tumor portfolio. We believe having full control of the development and commercialization of TEVIMBRA will allow us to rapidly accelerate our plans and reach more patients worldwide”

“We are excited to announce the European Commission approval and the FDA filing acceptance for tislelizumab, having recently regained full global rights to this important medicine. These are significant milestones for people with advanced or metastatic ESCC, as tislelizumab has been shown to deliver clinically meaningful survival benefit as monotherapy and in combination with chemotherapy in patients worldwide,” said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. “We are proud to bring this therapy to European patients and potentially to American patients and will continue to focus on ensuring that we develop tislelizumab to its full potential to address unmet clinical needs around the world.”

BeiGene has launched more than 20 potentially registration-enabling trials with TEVIMBRA, of which 10 Phase 3 randomized trials and four Phase 2 trials have already had positive readouts. Through these trials, TEVIMBRA has demonstrated its ability to safely deliver clinically meaningful improvements in survival benefits and quality of life for hundreds of thousands of cancer patients across a range of tumor types – in many cases, regardless of PD-L1 status – both as a monotherapy and in combination with other regimens. More than 750,000 patients have been prescribed TEVIMBRA to-date.

“TEVIMBRA is the cornerstone of BeiGene’s solid tumor portfolio. We believe having full control of the development and commercialization of TEVIMBRA will allow us to rapidly accelerate our plans and reach more patients worldwide,” said Josh Neiman, Chief Commercial Officer for North America and Europe at BeiGene. “We look forward to bringing TEVIMBRA to people living with advanced or metastatic ESCC, an aggressive disease with limited treatment options.”

TEVIMBRA Receives European Commission Approval for the Treatment of Advanced or Metastatic ESCC

The EC approval follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on positive results from BeiGene’s RATIONALE 302 study.

“The global RATIONALE 302 trial demonstrated the anti-PD-1 antibody tislelizumab prolonged the survival of patients with locally advanced or metastatic ESCC who had received prior systemic treatment, with no new safety signals identified,” said Prof. Florian Lordick, Director and Professor of Oncology of the University Cancer Center Leipzig, Germany. “The approval of tislelizumab in Europe is a noteworthy moment for patients, their caregivers and their physicians, due to the existing unmet need for new treatment options.”

RATIONALE 302 is a global, randomized, open-label, Phase 3 study (NCT03430843) designed to investigate the efficacy and safety of TEVIMBRA when compared with investigator’s choice chemotherapy as a second-line treatment for patients with unresectable, locally advanced or metastatic ESCC. The study enrolled 513 patients from 132 research sites in 11 countries in Europe, Asia and North America.

RATIONALE 302 met its primary endpoint in the intention-to-treat population with a statistically significant and clinically meaningful survival benefit for TEVIMBRA compared with chemotherapy (HR 0.70 [95% CI: 0.57 - 0.85]; one-sided P=0.0001; median overall survival 8.6 vs 6.3 months). The safety profile for TEVIMBRA was consistent with previous trials.i The marketing authorization application included safety data for 1,972 patients who received TEVIMBRA monotherapy across seven clinical trials.

U.S. FDA Accepts Biologics License Application in First-Line Advanced ESCC

The FDA has assigned a target action date in the second half of 2024, under the Prescription Drug User Fee Act. The FDA application is supported by previously announced results from RATIONALE 306 (NCT03783442), a randomized, placebo-controlled, double-blind, global Phase 3 trial evaluating the efficacy and safety of tislelizumab in combination with chemotherapy as a first-line treatment in patients with advanced or metastatic ESCC.

The FDA also granted tislelizumab Orphan Drug Designation (ODD) for the treatment of previously untreated advanced or metastatic ESCC. The FDA’s ODD is granted to investigational therapies intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the U.S.ii

About ESCC
Globally, esophageal cancer (EC) is the sixth most common cause of cancer-related deaths, and ESCC is the most common histologic subtype, accounting for more than 85% of ECs. An estimated 957,000 new EC cases are projected in 2040, an increase of nearly 60% from 2020 that underscores the need for additional effective treatments.iii EC is a rapidly fatal disease, and more than two-thirds of the patients have advanced or metastatic disease at the time of diagnosis, with a median survival of eight to 10 months and an expected five-year survival rate of less than five percent.iv

About TEVIMBRA (tislelizumab)
TEVIMBRA is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors. In pre-clinical studies, binding to Fcγ receptors on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells.

TEVIMBRA is currently under review by the U.S. Food and Drug Administration (FDA) and received approval by the European Commission (EC) for advanced or metastatic esophageal squamous cell carcinoma (ESCC) after prior chemotherapy. The EMA is reviewing a marketing authorization application for TEVIMBRA as a treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy, and in combination with chemotherapy for previously untreated locally advanced or metastatic NSCLC. Regulatory submissions for TEVIMBRA are also under review by authorities in the U.K., Australia, China, New Zealand, Brazil, Korea, Switzerland, Israel and Indonesia. Tislelizumab is approved as a treatment in 11 indications in China and is the leading PD-1 inhibitor in the country.

The tislelizumab development program encompasses 21 registration-enabling clinical trials in more than 30 countries and regions. To date, BeiGene has announced positive readouts from 10 Phase 3 pivotal studies across multiple tumor types and disease settings such as NSCLC, small cell lung cancer, gastric cancer, ESCC, hepatocellular cancer, and nasopharyngeal cancer. More information on the clinical trial program for tislelizumab can be found at: https://www.beigene.com/en-us/science-and-product-portfolio/pipeline.

About BeiGene
BeiGene is a global biotechnology company that is discovering and developing innovative oncology treatments that are more affordable and accessible to cancer patients worldwide. With a broad portfolio, we are expediting development of our diverse pipeline of novel therapeutics through our internal capabilities and collaborations. We are committed to radically improving access to medicines for far more patients who need them. Our growing global team of more than 10,000 colleagues spans five continents, with administrative offices in Basel, Beijing, and Cambridge, U.S. To learn more about BeiGene, please visit www.beigene.com and follow us on LinkedIn and X (formerly known as Twitter).

FDA grants accelerated approval to Pfizer's Elrexfio for r/r multiple myeloma

On August 14, 2023, the Food and Drug Administration granted accelerated approval to elranatamab-bcmm (Elrexfio, Pfizer, Inc.), a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, for adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

View full prescribing information for Elrexfio.

Efficacy was evaluated in MagnetisMM-3 (NCT04649359), an open-label, single-arm, multi-center study that included patients with relapsed/refractory MM who are refractory to at least one proteasome inhibitor, one immunomodulatory drug, and one anti-CD38 antibody. Patients had measurable disease by International Myeloma Working Group (IMWG) criteria at enrollment.

The main efficacy outcome measures were objective response rate (ORR) and duration of response (DOR), as assessed by a blinded independent central review based on IMWG criteria. The primary efficacy population consisted of 97 patients naïve to prior BCMA-directed therapy and who had previously received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The ORR in the 97 patients receiving the recommended dose was 57.7% (95% CI: 47.3%, 67.7%). With a median follow-up of 11.1 months among responders, the median DOR was not reached (95% CI: 12 months, not reached). The DOR rate at 6 months was 90.4% (95% CI: 78.4%, 95.9%) and at 9 months was 82.3% (95% CI: 67.1%, 90.9%).

The prescribing information for elranatamab-bcmm has a Boxed Warning for life threatening or fatal cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS). Among patients who received elranatamab-bcmm at the recommended dose, CRS occurred in 58% of patients, neurologic toxicity in 59%, and ICANS in 3.3%. Grade 3 CRS occurred in 0.5% of patients and Grade 3 or 4 neurologic toxicity occurred in 7%.

Because of the risks of CRS and neurologic toxicity, including ICANS, elranatamab-bcmm is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the ELREXFIO REMS.

The most common adverse reactions (≥20%) were CRS, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and pyrexia. The most common Grade 3 to 4 laboratory abnormalities (≥20%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets.

The recommended elranatamab-bcmm dosages include the following: “step-up dose 1” of 12 mg on Day 1, “step-up dose 2” of 32 mg on Day 4, followed by the first treatment dose of 76 mg on Day 8, and then 76 mg weekly, thereafter, through week 24. For patients who have received at least 24 weeks of elranatamab-bcmm and have achieved partial responses or better and maintained responses for at least 2 months, the dose interval should transition to an every two-week schedule. Elranatamab-bcmm may be continued until disease progression or unacceptable toxicity.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), the Brazilian Health Regulatory Agency (ANVISA), Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.

U.S. FDA Approves TALVEY™ (talquetamab-tgvs), a First-in-Class Bispecific Therapy for the Treatment of Patients with Heavily Pretreated Multiple Myeloma

Gavreto confirms benefit in NSCLC less than 3 years after initial accelerated approval

On August 9, 2023, the Food and Drug Administration granted regular approval to pralsetinib (Gavreto, Genentech, Inc.) for adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.

Pralsetinib was previously granted accelerated approval for the NSCLC indication on Sept. 4, 2020, based on initial overall response rate (ORR) and duration of response (DOR) in 114 patients enrolled in the ARROW trial (NCT03037385), a multicenter, open-label, multi-cohort trial. The conversion to regular approval was based on data from an additional 123 patients and 25 months of additional follow-up to assess durability of response.

View full prescribing information for Gavreto.

Efficacy was demonstrated in a total of 237 patients with locally advanced or metastatic RET fusion-positive NSCLC. Patients received pralsetinib until disease progression or unacceptable toxicity.

The primary efficacy measures were ORR and DOR as determined by a Blinded Independent Review Committee (BIRC). Among 107 treatment-naïve patients, ORR was 78% (95% CI: 68, 85) with a median DOR of 13.4 months (95% CI: 9.4, 23.1). Among 130 patients previously treated with platinum-based chemotherapy, ORR was 63% (95% CI: 54, 71) with a median DOR of 38.8 months (95% CI: 14.8, not estimable).

The most common adverse reactions (≥ 25%) were musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, pyrexia, and cough.

The recommended pralsetinib dose is 400 mg orally once daily. Pralsetinib is taken on an empty stomach (no food intake for at least 2 hours before and at least 1 hour after taking pralsetinib).

FDA Approves Daiichi Sankyo's NME quizartinib in frontline AML

On July 20, 2023, the Food and Drug Administration approved quizartinib (Vanflyta, Daiichi Sankyo, Inc.) with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3 internal tandem duplication (ITD)-positive, as detected by an FDA-approved test.

FDA also approved LeukoStrat CDx FLT3 Mutation Assay as a companion diagnostic for Vanflyta.

View full prescribing information for Vanflyta.

Efficacy of quizartinib with chemotherapy was evaluated in QuANTUM-First (NCT02668653), a randomized, double-blind, placebo-controlled trial of 539 patients with newly diagnosed FLT3-ITD positive AML. FLT3-ITD status was determined prospectively with a clinical trial assay and verified retrospectively with the companion diagnostic LeukoStrat CDx FLT3 Mutation Assay.

Patients were randomized (1:1) to receive quizartinib (n=268) or placebo (n=271) with induction and consolidation therapy and as maintenance monotherapy according to the initial assignment. There was no re-randomization at the initiation of post-consolidation therapy. Patients who proceeded to hematopoietic stem cell transplantation (HSCT) initiated maintenance therapy after HSCT recovery.

The main efficacy outcome measure was overall survival (OS), measured from randomization date until death by any cause. The primary analysis was conducted after a minimum follow-up of 24 months after the last patient was randomized. The trial demonstrated a statistically significant improvement in OS for the quizartinib arm [hazard ratio (HR) 0.78; 95% CI: 0.62, 0.98; 2‑sided p=0.0324]. The CR rate in the quizartinib arm was 55% (95% CI: 48.7, 60.9) with a median duration of 38.6 months (95% CI: 21.9, NE), and the CR rate in those receiving placebo was 55% (95% CI: 49.2, 61.4) with a median duration of 12.4 months (95% CI: 8.8, 22.7).

Quizartinib is not indicated as maintenance monotherapy following allogeneic HSCT. Improvement in OS with quizartinib has not been demonstrated in this setting.

A boxed warning for quizartinib notes QT prolongation, torsades de pointes, and cardiac arrest. Quizartinib is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the Vanflyta REMS. See the prescribing information for the full list of adverse reactions.

The recommended quizartinib dose is as follows:

• Induction: 35.4 mg orally once daily on Days 8-21 of “7 + 3” (cytarabine [100 or 200 mg/m2/day] on Days 1 to 7 plus daunorubicin [60 mg/m2/day] or idarubicin [12 mg/m2/day] on Days 1 to 3) and on Days 8-21 or 6-19 of an optional second induction (“7 + 3” or “5 + 2” [5 days cytarabine plus 2 days daunorubicin or idarubicin], respectively),

• b) Consolidation: 35.4 mg orally once daily on Days 6-19 of high‑dose cytarabine (1.5 to 3 g/m2 every 12 hours on Days 1, 3 and 5) for up to 4 cycles, and

• c) Maintenance: 26.5 mg orally once daily on Days 1 to 14 and 53 mg once daily, thereafter, for up to thirty-six 28-day cycles.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted priority review, fast track designation and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

EU approves Roche’s Columvi (glofitamab) CMA for r/r DLBCL; Orphan Maintained

• Columvi is the first CD20xCD3 T-cell-engaging bispecific antibody available in Europe to treat the most common and aggressive form of lymphoma

• Approval is based on results from the phase I/II NP30179 study, where Columvi given as a fixed course induced early and long-lasting complete responses in people with heavily pre-treated or refractory diffuse large B-cell lymphoma1

• Columvi is given for a fixed period of time and made to be readily available, providing patients with a treatment end date and treatment-free period

Basel, 11 July 2023 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the European Commission (EC) has granted conditional marketing authorisation for Columvi® (glofitamab) for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy. With this approval, Columvi is the first CD20xCD3 T-cell-engaging bispecific antibody available to treat people in Europe with the most common and aggressive form of lymphoma following multiple lines of therapy. Columvi has the potential to change the current standard of care in DLBCL. As well as inducing early and long-lasting responses in people with heavily pre-treated or refractory DLBCL, Columvi is designed to be given for a fixed period of time meaning that people have a target end date for their course of treatment and the possibility of a treatment-free period. It is also a chemotherapy-free treatment option that is off-the-shelf, meaning that people do not have to wait for cell collection and genetic engineering - a multistep process that can take several weeks - before starting treatment. This could be particularly important for patients who are at a high-risk of their disease progressing.

DLBCL is an aggressive (fast-growing) type of lymphoma and is one of the most prevalent types of blood cancer among adults.2 Each year in Europe, an estimated 36,000 people are diagnosed with DLBCL.3 While many patients with DLBCL are responsive to initial treatment, four out of ten are not cured with the current standard of care, frontline treatment, and the majority of patients who require subsequent lines of therapy have poor outcomes.4,5

“As pioneers in the development of innovative T-cell-engaging bispecific antibodies, we are delighted that we can now offer Columvi as the first approved treatment of its kind to people in Europe,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “We are confident that thanks to its off-the-shelf availability, fixed-duration regimen and durability, Columvi will positively transform the treatment experience for relapsed or refractory diffuse large B-cell lymphoma.”

“As the lead investigator for the NP30179 study, I have seen first-hand the early and long-lasting responses that Columvi can induce, when given to patients for a fixed period of time,” said Michael Dickinson, M.D., Ph.D., principal study investigator and Associate Professor, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Australia. “It is exciting that with this approval, patients in Europe with heavily pre-treated or refractory diffuse large B-cell lymphoma will now have a new, potentially practice-changing treatment option that will allow them time off of therapy to resume their routine activities, helping to alleviate some of the physical and emotional burdens caused by cancer treatment.”

The approval is based on positive results from a pivotal cohort in the phase I/II NP30179 study, where Columvi given as a fixed course induced early and long-lasting responses in people with R/R DLBCL. Overall, 83.3% of patients were refractory to their most recent therapy, 90% were refractory to any previous line of therapy, and about one-third (35.2%) had received prior CAR T-cell therapy. Results showed that Columvi given as a fixed course, induced a complete response (CR; a disappearance of all signs of cancer) in 35.2% (n =38/108) of people, and 50% (n=54/108) achieved an overall response (OR; the combination of CR and partial response, a decrease in the amount of cancer in their body). Among those who achieved a CR, 74.6% (95% CI: 59.19-89.93) continued to experience a response at 12 months, while the median duration of CR was not reached. The median follow-up for duration of response (DOR) was 12.8 months. Median time to first CR was 42 days (95% CI: 41-47). The most common adverse events (AEs) were cytokine release syndrome (CRS; 64.3%), neutropenia (a reduction in white blood cells [37.7%]), anaemia (30.5%) and thrombocytopenia (low blood platelet count [24.7%]). CRS was generally low grade (Grade 1: 48.1%; Grade 2: 12.3%). One patient discontinued treatment due to CRS.1

Additional data from a larger cohort in the NP30179 study, published in the New England Journal of Medicine reinforce the durability of Columvi. Fixed-duration Columvi resulted in early and long-lasting responses in people with heavily pre-treated or refractory DLBCL, with 39.4% of patients (n=61/155) achieving a CR and a median DOR of 18.4 months. Median time to CR was 42 days (95% CI: 42-44), with the majority of responses reported at the first scheduled response assessment (approximately 1.4 months after the start of treatment). Half of patients (51.6%; n=80/155) achieved an OR. The most common AE was CRS, which was generally low grade (Grade 1: 47.4%; Grade 2: 11.7%) and occurred at initial doses. Columvi-related AEs leading to treatment discontinuation occurred in 3.2% of patients.6

The U.S. Food and Drug Administration (FDA) recently approved Columvi for the treatment of adult patients with R/R DLBCL not otherwise specified or large B-cell lymphoma (LBCL) arising from FL, after two or more lines of systemic therapy for the treatment of people with R/R large B cell lymphoma. Columvi is also approved in Canada for the treatment of adult patients with R/R DLBCL not otherwise specified, DLBCL arising from follicular lymphoma (FL), or primary mediastinal B-cell lymphoma, who have received two or more lines of systemic therapy and are ineligible to receive or cannot receive CAR T-cell therapy or have previously received CAR T-cell therapy. Submissions to additional health authorities worldwide are ongoing.

Roche is continually building on its long-standing expertise in haematology by investigating innovative solutions that redefine treatment standards for patients and improve on existing standards of care. In a broad and industry-leading CD20xCD3 T-cell-engaging bispecific antibody clinical development programme, Roche is exploring the potential of both Columvi and Lunsumio® (mosunetuzumab) in earlier lines of treatment and in combination with other novel and chemotherapy-free agents, such as Polivy® (polatuzumab vedotin), with the goal of providing patients with long-lasting outcomes.

Roche continues to expand Columvi’s clinical development programme, which includes the phase III STARGLO trial, evaluating Columvi in combination with gemcitabine and oxaliplatin (GemOx) versus rituximab in combination with GemOx in patients with second-line plus DLBCL who are ineligible for autologous stem cell transplant. Additional phase III studies are also planned, including in first-line DLBCL.

About Columvi® (glofitamab)
Columvi is a CD20xCD3 T-cell-engaging bispecific antibody designed to target CD3 on the surface of T-cells and CD20 on the surface of B-cells. Columvi was designed with a novel 2:1 structural format. This T-cell-engaging bispecific antibody is engineered to have one region that binds to CD3, a protein on T-cells, a type of immune cell, and two regions that bind to CD20, a protein on B-cells, which can be healthy or malignant. This dual-targeting brings the T-cell in close proximity to the B-cell, activating the release of cancer cell-killing proteins from the T-cell. A clinical development programme for Columvi is ongoing, investigating the molecule as a monotherapy and in combination with other medicines for the treatment of people with B-cell non-Hodgkin lymphomas, including diffuse large B-cell lymphoma and other blood cancers.

About the NP30179 study
The NP30179 study [NCT03075696] is a phase I/II, multicentre, open-label, dose-escalation and expansion study evaluating the safety, efficacy and pharmacokinetics of Columvi® (glofitamab) in people with relapsed or refractory diffuse large B-cell lymphoma. Outcome measures include complete response rate by an independent review committee (primary endpoint), overall response rate, duration of response, progression-free survival, safety, and tolerability (secondary endpoints).

About diffuse large B-cell lymphoma (DLBCL)
DLBCL is the most common form of non-Hodgkin lymphoma (NHL), accounting for about one in three cases of NHL.2 DLBCL is an aggressive (fast-growing) type of NHL.2 While it is generally responsive to treatment in the frontline, as many as 40% of people will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short.4,5 Improving treatments earlier in the course of the disease and providing needed alternative options could help to improve long-term outcomes. Each year in Europe, it is estimated that 36,000 people are diagnosed with DLBCL.3

About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for more than 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera®/Rituxan® (rituximab), Gazyva®/Gazyvaro® (obinutuzumab), Polivy® (polatuzumab vedotin), Venclexta®/Venclyxto® (venetoclax) in collaboration with AbbVie, Hemlibra® (emicizumab), Lunsumio® (mosunetuzumab) and Columvi® (glofitamab). Our pipeline of investigational haematology medicines includes a T-cell-engaging bispecific antibody cevostamab, targeting both FcRH5 and CD3; Tecentriq® (atezolizumab), a monoclonal antibody designed to bind with PD-L1 and crovalimab, an anti-C5 antibody engineered to optimise complement inhibition. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.

FDA converts BLINCYTO (blinatumomab) to full approval for the treatment of adults and pediatric patients with MRD-positive ALL

Conversion From Accelerated to Full Approval

Reinforces BLINCYTO as Standard of Care for Patients With Minimal Residual Disease at Baseline After Remission

THOUSAND OAKS, Calif., June 21, 2023 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental Biologics License Application (sBLA) for BLINCYTO® (blinatumomab) for the treatment of adults and pediatric patients with CD19-positive B-cell precursor acute lymphoblastic leukemia (B-ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%, based on additional data from two Phase 3 studies that were submitted. The approval converts BLINCYTO's accelerated approval to a full approval. 

"We are pleased the FDA has granted full approval for BLINCYTO, the first FDA-approved CD19-directed CD3 T-cell engager BiTE® immunotherapy and the first to be FDA-approved for MRD in 2018," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "Today's full approval underscores the clinical benefit of BLINCYTO for people living with B-ALL, and we look forward to exploring how we can continue to make a significant impact for these patients."

 Amgen continues to advance a robust development program for BLINCYTO, including studies aimed at treating patients with MRD-negative B-ALL, trials designed to minimize chemotherapy, and the clinical investigation of a subcutaneous formulation, all intended to help address remaining unmet needs for patients.

"In a Phase 2 study, roughly 80% of adult patients treated with blinatumomab experienced a complete MRD response," said principal investigator Elias Jabbour, M.D., Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston. "The FDA's decision to grant a full approval for blinatumomab further validates the use of this therapy to treat adults and children with B-cell precursor ALL with MRD present following a remission, which is a strong predictor of relapse in this patient population."

About BLINCYTO® (blinatumomab)
BLINCYTO is a BiTE® (bispecific T-cell engager) immuno-oncology therapy that targets CD19 surface antigens on B cells. BiTE molecules fight cancer by helping the body's immune system detect and target malignant cells by engaging T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. By bringing T cells near cancer cells, the T cells can inject toxins and trigger cancer cell death (apoptosis). BiTE immuno-oncology therapies are currently being investigated for their potential to treat a wide variety of cancers.

BLINCYTO was granted breakthrough therapy and priority review designations by the U.S. Food and Drug Administration and is approved in the U.S. for the treatment of:

• CD19-positive B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% in adults and pediatric patients.

• relapsed or refractory CD19-positive B-cell precursor ALL in adults and pediatric patients.

In the European Union (EU), BLINCYTO is indicated as monotherapy for the treatment of:

• adults with Philadelphia chromosome-negative CD19 positive relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL).

• adults with Philadelphia chromosome-negative CD19 positive B-precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%.

• pediatric patients aged 1 year or older with Philadelphia chromosome negative CD19 positive B-precursor ALL which is refractory or in relapse after receiving at least two prior therapies or in relapse after receiving prior allogeneic hematopoietic stem cell transplantation.

IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES

• Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® and treat with corticosteroids as recommended.

• Neurological toxicities, which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® as recommended.

Contraindications

BLINCYTO® is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Warnings and Precautions

• Cytokine Release Syndrome (CRS): CRS, which may be life-threatening or fatal, occurred in 15% of patients with R/R ALL and in 7% of patients with MRD-positive ALL. The median time to onset of CRS is 2 days after the start of infusion and the median time to resolution of CRS was 5 days among cases that resolved. Closely monitor and advise patients to contact their healthcare professional for signs and symptoms of serious adverse events such as fever, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), and disseminated intravascular coagulation (DIC). The manifestations of CRS after treatment with BLINCYTO® overlap with those of infusion reactions, capillary leak syndrome, and hemophagocytic histiocytosis/macrophage activation syndrome. If severe CRS occurs, interrupt BLINCYTO® until CRS resolves. Discontinue BLINCYTO® permanently if life-threatening CRS occurs. Administer corticosteroids for severe or life-threatening CRS. 

• Neurological Toxicities: Approximately 65% of patients receiving BLINCYTO® in clinical trials experienced neurological toxicities. The median time to the first event was within the first 2 weeks of BLINCYTO® treatment and the majority of events resolved. The most common (≥ 10%) manifestations of neurological toxicity were headache and tremor. Severe, life-threatening, or fatal neurological toxicities occurred in approximately 13% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. Manifestations of neurological toxicity included cranial nerve disorders. Monitor patients for signs or symptoms and interrupt or discontinue BLINCYTO® as outlined in the PI. 

• Infections: Approximately 25% of patients receiving BLINCYTO® in clinical trials experienced serious infections such as sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-site infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO® as needed.

• Tumor Lysis Syndrome (TLS), which may be life-threatening or fatal, has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on-treatment hydration, should be used during BLINCYTO® treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO® as needed to manage these events.

• Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters (including, but not limited to, white blood cell count and absolute neutrophil count) during BLINCYTO® infusion and interrupt BLINCYTO® if prolonged neutropenia occurs.

• Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures, patients receiving BLINCYTO® are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO® is being administered.

• Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO® treatment with a median time to onset of 3 days. In patients receiving BLINCYTO®, although the majority of these events were observed in the setting of CRS, some cases of elevated liver enzymes were observed outside the setting of CRS, with a median time to onset of 19 days. Grade 3 or greater elevations in liver enzymes occurred in approximately 7% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase, and TBILI prior to the start of and during BLINCYTO® treatment. BLINCYTO® treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN.

• Pancreatitis: Fatal pancreatitis has been reported in patients receiving BLINCYTO® in combination with dexamethasone in clinical trials and the post-marketing setting. Evaluate patients who develop signs and symptoms of pancreatitis and interrupt or discontinue BLINCYTO® and dexamethasone as needed.

• Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO®, especially in patients previously treated with cranial irradiation and antileukemic chemotherapy.

• Preparation and administration errors have occurred with BLINCYTO® treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).

• Immunization: Vaccination with live virus vaccines is not recommended for at least 2 weeks prior to the start of BLINCYTO® treatment, during treatment, and until immune recovery following last cycle of BLINCYTO®

• Benzyl Alcohol Toxicity in Neonates: Serious adverse reactions, including fatal reactions and the "gasping syndrome," have been reported in very low birth weight (VLBW) neonates born weighing less than 1500 g, and early preterm neonates (infants born less than 34 weeks gestational age) who received intravenous drugs containing benzyl alcohol as a preservative. Early preterm VLBW neonates may be more likely to develop these reactions, because they may be less able to metabolize benzyl alcohol.
  
  Use the preservative-free preparations of BLINCYTO® where possible in neonates. When prescribing BLINCYTO® (with preservative) for neonatal patients, consider the combined daily metabolic load of benzyl alcohol from all sources including BLINCYTO® (with preservative), other products containing benzyl alcohol or other excipients (e.g., ethanol, propylene glycol) which compete with benzyl alcohol for the same metabolic pathway.
  
  Monitor neonatal patients receiving BLINCYTO® (with preservative) for new or worsening metabolic acidosis. The minimum amount of benzyl alcohol at which serious adverse reactions may occur in neonates is not known. The BLINCYTO® 7-Day bag (with preservative) contains 7.4 mg of benzyl alcohol per mL.

• Embryo-Fetal Toxicity: Based on its mechanism of action, BLINCYTO® may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with BLINCYTO® and for 48 hours after the last dose.

 Adverse Reactions

• The most common adverse reactions (≥ 20%) are pyrexia, infusion-related reactions, infections (pathogen unspecified), headache, neutropenia, anemia, and thrombocytopenia.

Dosage and Administration Guidelines

• BLINCYTO® is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm.

• It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).

Please see BLINCYTO® full Prescribing Information, including BOXED WARNINGS, at www.BLINCYTO.com.

About BiTE® Technology

BiTE® (bispecific T-cell engager) technology is a targeted immuno-oncology platform that is designed to engage patient's own T cells to any tumor-specific antigen, activating the cytotoxic potential of T cells to eliminate detectable cancer. The BiTE immuno-oncology platform has the potential to treat different tumor types through tumor-specific antigens. The BiTE platform has a goal of leading to off-the-shelf solutions, which have the potential to make innovative T cell treatment available to all providers when their patients need it. Amgen is advancing more than a dozen BiTE molecules across a broad range of hematologic malignancies and solid tumors, further investigating BiTE technology with the goal of enhancing patient experience and therapeutic potential. To learn more about BiTE technology, visit www.AmgenBiTETechnology.com.

About Amgen 

Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology. 

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential. 

Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average and is also part of the Nasdaq-100 index. In 2022, Amgen was named one of the "World's Best Employers" by Forbes and one of "America's 100 Most Sustainable Companies" by Barron's.

For more information, visit Amgen.com and follow us on Twitter, LinkedIn, Instagram, TikTok and YouTube.

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