On September 25, 2023 Glycotope GmbH (Glycotope) and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association reported to have signed an agreement to explore the potential of combining Glycotope’s antibodies against protein/carbohydrate combined glyco-epitopes (GlycoTargets) with chimeric antigen receptor (CAR) technology developed by the Max Delbrück Center (Press release, Glycotope, SEP 25, 2023, View Source [SID1234635384]).

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CARs are engineered synthetic receptors that function to redirect lymphocytes, most commonly T-cells, to recognise and eliminate cells expressing a specific target antigen. These cell-based therapies have demonstrated exciting results in clinical trials and are rapidly becoming powerful alternatives to conventional treatments for hematologic cancers in particular. However, in some indications, including harder to treat cancers with solid tumors, success has been limited. A major problem facing drug developers is the selection of suitable antigens that are only expressed on tumors, and can therefore be targeted safely. In the scope of the newly established collaboration, highly tumor-specific antibodies developed by Glycotope will be combined with the CAR technology of the Max Delbrück Center to analyze their suitability for the treatment of solid tumors.

"CAR-T cells have dramatically improved the treatment of hematologic malignancies. In stark contrast, CAR-T cells lack efficacy against solid tumors, which by far outnumber incidence and mortality rates of leukemia and lymphoma. Epidemiologically, breast, lung, prostate, and colon cancers are the most common "killers" which cannot be successfully targeted using current T cell therapies," said Dr Armin Rehm, who heads the Translational Tumorimmunology Lab at the Max Delbrück Center. "But antibodies can recognize tumor-associated aberrant glycosylation, making it an attractive and tumor-specific target structure.This feature, together with a broad tumor-specific expression, paves the way for the generation of glycan-redirected CAR-T and NK cells. Thus, we are joining forces for a new generation of CAR-T and NK cells," said Dr Höpken, Head of the Lab Environmental Regulation in Autoimmunity and Cancer at the Max Delbrück Center, and Dr Rehm.

"We are pleased to have gained another renowned collaboration partner and look forward to working with the experienced scientists from Uta’s and Armin’s groups to evaluate how our targeting approach can help advance cellular therapies for solid tumors," added Dr Patrik Kehler, CSO at Glycotope.

Glycotope’s antibodies target specific tumor-associated carbohydrate structures or protein/carbohydrate combined glyco-epitopes (GlycoTargets). Targeting these specific antigens enables broad indication range, long-term treatment potential and reduced on-target/off tumor toxicity, key elements of highly potent therapies. Based on this unrivalled tumor-specificity, Glycotope’s antibodies are highly suitable for a multi-function platform approach with independent modes of action to provide a tailored therapy format for as many patients as possible.

The CAR program at the Max Delbrück Center includes several proprietary antibody binders targeting hematologic tumors. This program involves the development of a full preclinical validation, a clinical scale automated manufacturing platform, and the initiation of two phase I/II clinical trials in collaboration with clinical partners. A comprehensive molecular toolbox of modular CAR components enables rapid integration of new antibody binders. Extensive experience in CAR design, retroviral engineering for CAR transfer, regulatory advice by authorities, and established methodologies to generate T cell and NK cell effector populations for in vitro and in vivo testing will facilitate the implementation of innovative antibodies in our next-generation CAR platform, targeting tumor-associated glycan structures.

On September 25, 2023 Genmab A/S (Nasdaq: GMAB) reported that the European Commission (EC) has granted conditional marketing authorization for TEPKINLY (epcoritamab) as a monotherapy 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 (Press release, Genmab, SEP 25, 2023, View Source [SID1234635382]). TEPKINLY is the first and only subcutaneous T-cell engaging bispecific antibody approved for the treatment of this patient population in the European Union (EU), as well as Liechtenstein, Norway and Iceland.

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DLBCL is the most common type of B-cell non-Hodgkin’s lymphoma worldwide. While patients may have access to chemoimmunotherapy regimens to treat their disease, they face limited treatment options, with few readily available, off-the-shelf medicines, especially for those whose disease has relapsed or become refractory to prior treatments.i

"With TEPKINLY, people in Europe living with relapsed or refractory diffuse large B-cell lymphoma who are in need of additional treatment options now have a readily available, innovative therapeutic option for this aggressive cancer," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "Today’s approval underscores our commitment to bringing our bispecific antibody to more patients worldwide. We’re excited to continue working with our partner AbbVie to further explore epcoritamab as potential core therapy across B-cell malignancies."

This conditional approval is supported by data from the pivotal EPCORE NHL-1 phase 1/2 open-label, multi-cohort, multi-center, single-arm trial evaluating the preliminary efficacy and safety of TEPKINLY in patients with R/R large B-cell lymphoma (LBCL), including its subtype DLBCL. In this study, DLBCL patients treated with TEPKINLY (n=139) achieved an overall response rate of 62 percent (n=86) and a complete response rate of 39 percent (n=54), with a median duration of response of 15.5 months (range: 9.7, not reached).

Results from the trial showed that TEPKINLY demonstrated a manageable safety profile across the LBCL patient cohort (n=167), which included the DLBCL patient population. The most common adverse reactions (≥ 20 percent) were cytokine release syndrome, fatigue, neutropenia, injection site reaction, musculoskeletal pain, abdominal pain, pyrexia, nausea and diarrhea.

"Relapsed or refractory DLBCL is an aggressive cancer and patients can face a difficult and emotional treatment journey. At this point in the journey, a patient may have had multiple lines of therapy and will already have experienced relapse," said Anna Sureda, M.D., Ph.D., head of clinical hematology department, Institut Català d’Oncologia – L’Hospitalet, Barcelona, Spain. "This European Commission approval represents an important moment for the DLBCL patient community and brings with it a potential opportunity for effective disease management for a condition with limited available treatment options."

Conditional marketing authorization is granted to medicines that address an unmet medical need, where the benefit of its immediate availability to patients outweighs the risk of limited data availability, and where confirmatory comprehensive data will need to be provided subsequently to maintain the marketing authorization.ii

Epcoritamab is being co-developed by AbbVie and Genmab as part of the companies’ oncology collaboration. The companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization. AbbVie will continue to pursue regulatory submissions for epcoritamab across international markets throughout the year.

About the EPCORE NHL-1 Trial
EPCORE NHL-1 is an open-label, multi-center preliminary efficacy and safety trial of epcoritamabthat includes a phase 1 first-in-human, dose escalation part; a phase 2a expansion part; and a dose optimization part. The trial was designed to evaluate subcutaneous epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin’s lymphoma (NHL), including large B-cell lymphoma (LBCL) and diffuse large B-cell lymphoma (DLBCL).iii Data from the dose escalation part of the study, which determined the recommended phase 2 dose, were published in September 2021.iv In the phase 2 expansion part, additional patients were treated with epcoritamab to further explore the efficacy and safety of epcoritamab in three cohorts of patients with different types of relapsed or refractory (R/R) B-cell NHLs who had limited therapeutic options.iii

The median number of prior therapies was three (range: 2 to 11), with 30 percent receiving two prior therapies, 30 percent receiving three prior therapies, and 40 percent receiving four or more prior therapies. Eighteen percent had prior autologous hematopoietic stem cell transplantation (HSCT), and 39 percent had prior chimeric antigen receptor (CAR) T-cell therapy. Eighty-two percent of patients had disease refractory to last therapy and 29 percent of patients were refractory to CAR T-cell therapy.

The primary endpoint of the phase 2 expansion part was overall response rate as assessed by an independent review committee. Secondary efficacy endpoints included duration of response, complete response rate, progression-free survival, overall survival, time to response, time to next therapy, and rate of minimal residual disease negativity. More information can be found on www.clinicaltrials.gov.

About TEPKINLY (epcoritamab)
Epcoritamab is an IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T-cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T-cells and CD20 on B-cells and induces T-cell mediated killing of CD20+ cells.v CD20 is expressed on B-cells and is a clinically validated therapeutic target in many B-cell malignancies, including DLBCL, follicular lymphoma, mantle cell lymphoma and chronic lymphocytic leukemia.vi,vii

Epcoritamab-bysp (EPKINLYTM) was approved under accelerated approval in the United States in May 2023. Continued approval is contingent upon verification and description of clinical benefit in a confirmatory trial(s). For more information, please see the Full Prescribing Information and Medication Guide, including Important Warnings.

Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes three ongoing phase 3, open-label, randomized trials including a trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL (NCT: 04628494) compared to investigators choice chemotherapy, a phase 3, trial evaluating epcoritamab in combination with R-CHOP in adult participants with newly diagnosed DLBCL (NCT: 05578976), and a phase 3, open-label clinical trial evaluating epcoritamab in combination in patients with R/R follicular lymphoma (FL) (NCT: 05409066). Epcoritamab is not approved to treat newly diagnosed patients with DLBCL or FL. The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit clinicaltrials.gov for more information.

EU Indications and Important Safety Information about Tepkinly q (epcoritamab)

Indications
Tepkinly (epcoritamab) as monotherapy is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy.

Important Safety Information

Contraindications
Hypersensitivity to the active substance or to any of the excipients.

Special warnings and precautions for use
Cytokine release syndrome (CRS)
CRS, which may be life-threatening or fatal, occurred in patients receiving Tepkinly. The most common signs and symptoms of CRS include pyrexia, hypotension and hypoxia. Other signs and symptoms of CRS in more than two patients include chills, tachycardia, headache and dyspnoea.

Most CRS events occurred in Cycle 1 and were associated with the first full dose of Tepkinly. Administer prophylactic corticosteroids to mitigate the risk of CRS. Patients should be monitored for signs and symptoms of CRS following Tepkinly administration. Patients should be hospitalised for 24 hours after administration of the Cycle 1 Day 15 dose of 48 mg to monitor for signs and symptoms of CRS. At the first signs or symptoms of CRS, institute treatment of supportive care with tocilizumab and/or corticosteroids as appropriate. Patients should be counselled on the signs and symptoms associated with CRS and patients should be instructed to contact their healthcare professional and seek immediate medical attention should signs or symptoms occur at any time. Management of CRS may require either temporary delay or discontinuation of Tepkinly based on the severity of CRS.

Immune effector cell-associated neurotoxicity syndrome (ICANS)
ICANS, including a fatal event, have occurred in patients receiving Tepkinly. ICANS may manifest as aphasia, altered level of consciousness, impairment of cognitive skills, motor weakness, seizures, and cerebral oedema. The majority of cases of ICANS occurred within Cycle 1 of Tepkinly treatment, however some occurred with delayed onset. Patients should be monitored for signs and symptoms of ICANS following Tepkinly administration. Patients should be hospitalised for 24 hours after administration of the Cycle 1 Day 15 dose of 48 mg to monitor for signs and symptoms of ICANS. At the first signs or symptoms of ICANS treatment with corticosteroids and non-sedating-anti-seizure medicinal products should be instituted as appropriate. Patients should be counselled on the signs and symptoms of ICANS and that the onset of events may be delayed. Patients should be instructed to contact their healthcare professional and seek immediate medical attention should signs or symptoms occur at any time. Tepkinly should be delayed or discontinued as recommended.

Serious infections
Treatment with Tepkinly may lead to an increased risk of infections. Serious or fatal infections were observed in patients treated with Tepkinly in clinical studies. Administration of Tepkinly should be avoided in patients with clinically significant active systemic infections. As appropriate, prophylactic antimicrobials should be administered prior to and during treatment with Tepkinly. Patients should be monitored for signs and symptoms of infection, before and after Tepkinly administration, and treated appropriately. In the event of febrile neutropenia, patients should be evaluated for infection and managed with antibiotics, fluids and other supportive care, according to local guidelines.

Tumour Lysis Syndrome (TLS)
TLS has been reported in patients receiving Tepkinly. Patients at an increased risk for TLS are recommended to receive hydration and prophylactic treatment with a uric acid lowering agent. Patients should be monitored for signs or symptoms of TLS, especially patients with high tumour burden or rapidly proliferative tumours, and patients with reduced renal function. Patients should be monitored for blood chemistries and abnormalities should be managed promptly.

Tumour flare
Tumour flare has been reported in patients treated with Tepkinly. Manifestations could include localized pain and swelling. Consistent with the mechanism of action of Tepkinly, tumour flare is likely due to the influx of T-cells into tumour sites following Tepkinly administration. There are no specific risk factors for tumour flare that have been identified; however, there is a heightened risk of compromise and morbidity due to mass effect secondary to tumour flare in patients with bulky tumours located in close proximity to airways and/or a vital organ. Patients treated with Tepkinly should be monitored and evaluated for tumour flare at critical anatomical sites.

CD20-negative disease
There are limited data available on patients with CD20-negative DLBCL treated with Tepkinly, and it is possible that patients with CD20-negative DLBCL may have less benefit compared to patients with CD20-positive DLBCL. The potential risks and benefits associated with treatment of patients with CD20-negative DLBCL with Tepkinly should be considered.

Immunisation
Live and/or live-attenuated vaccines should not be given during Tepkinly therapy. Studies have not been conducted in patients who received live vaccines.

Fertility, pregnancy and lactation
Tepkinly is not recommended during pregnancy and in women of childbearing potential not using contraception.

Effects on ability to drive and use machines
Tepkinly has minor influence on the ability to drive and use machines. Due to the potential for ICANS, patients should be advised to exercise caution while (or avoid if symptomatic) driving, cycling or using heavy or potentially dangerous machines.

Undesirable effects
Summary of the safety profile
The most common adverse reactions (≥ 20%) were CRS, fatigue, neutropenia, injection site reactions, musculoskeletal pain, abdominal pain, pyrexia, nausea, and diarrhoea.

Serious adverse reactions occurred in 52% of patients. The most frequent serious adverse reaction (≥ 10%) was cytokine release syndrome (31%). Seven patients (4.2%) experienced a fatal adverse reaction (pneumonia in 3 (1.8%) patients, viral infection in 3 (1.8%) patients and ICANS in 1 (0.6%) patient). Adverse reactions that led to discontinuation occurred in 6.6% of patients. Discontinuation of Tepkinly due to pneumonia occurred in 6 (3.6%) patients, viral infection in 3 (1.8%) patients, and CRS, ICANS, or fatigue in 1 (0.6%) patient each. Dose delays due to adverse reactions occurred in 32% of patients. Adverse reactions leading to dose delays (≥ 3%) were viral infections (9.6%), CRS (7.2%), neutropenia (4.8%), pyrexia (3.0%), and thrombocytopenia (3.0%).

This is not a complete summary of all safety information.
See Tepkinly full Summary of Product Characteristics (SmPC) at www.ema.europa.eu
Globally, prescribing information varies; refer to the individual country product label for complete information.

On September 25, 2023 Genmab A/S (Nasdaq: GMAB) reported that the Japan Ministry of Health, Labour and Welfare has approved EPKINLYTM (epcoritamab) as the first and only T-cell engaging bispecific antibody treatment in Japan of adult patients with certain types of relapsed or refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL) and follicular lymphoma grade 3B (FL3B), after two or more lines of systemic therapy (Press release, Genmab, SEP 25, 2023, View Source [SID1234635381]). Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ oncology collaboration.

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"Despite recent advances in the treatment of LBCL, the prognosis for patients with relapsed/refractory LBCL remains generally poor, and there is a need for additional treatment options for patients whose condition has worsened after multiple lines of treatment," said Koji Izutsu, MD, PhD, principal investigator of the phase 1/2 EPCORE NHL-3 trial in Japan and Head of the Hematology Department, National Cancer Center Hospital. "In the EPCORE NHL-3 trial, subcutaneous epcoritamab monotherapy demonstrated responses in a considerable number of patients with relapsed/refractory DLBCL, indicating that this approval is of great significance."

The approval of EPKINLY in Japan is based on the results from two open-label, multi-center studies designed to evaluate the safety and preliminary efficacy of EPKINLY monotherapy in patients with R/R LBCL. In the phase 1/2 EPCORE NHL-1 trial, 157 patients with relapsed or refractory LBCL demonstrated an overall response rate (ORR) of 63 percent ([95 percent confidence interval (CI): 55.0-70.6]) and a complete response (CR) rate of 39 percent (data cutoff: January 31, 2022). Of 157 patients treated with EPKINLY, 130 (82.8 percent) experienced treatment related side effects. The most common side effects (>15 percent) included cytokine release syndrome (49.7 percent), injection site reactions (19.7 percent), and neutropenia (17.8 percent).

In the phase 1/2 EPCORE NHL-3 trial, 36 patients with relapsed or refractory DLBCL after two or more lines of treatment demonstrated similar results with an ORR of 56 percent ([95 percent CI: 38.1-72.1]) and a CR rate of 44 percent (data cutoff: January 31, 2022). Of 36 patients treated with EPKINLY, 36 (100 percent) experienced treatment related side effects. The most common side effects (>15 percent) included cytokine release syndrome (83.3 percent), injection site reactions (58.3 percent), neutropenia (30.6 percent), lymphopenia (19.4 percent), decreased appetite (19.4 percent), thrombocytopenia (19.4 percent), and rash (19.4 percent).

"This approval marks an important milestone for patients in Japan with relapsed/refractory large B-cell lymphoma who are in need of alternative therapeutic options and who may now have access to EPKINLY, the first approved T-cell engaging bispecific antibody," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "We are working closely with AbbVie to deliver EPKINLY to patients in Japan as quickly as possible and we remain committed to continue evaluating epcoritamab as a potential core therapy across B-cell malignancies."

About the EPCORETM NHL-3 Trial
EPCORETM NHL-3 is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab including a phase 1 first-in-human, dose escalation part; and a phase 2 expansion part. The trial was designed to evaluate subcutaneous epcoritamab in Japanese patients with relapsed, progressive or refractory mature B-NHL, including DLBCL. In the phase 2 expansion part, additional patients are treated with epcoritamab to further explore the safety and efficacy of epcoritamab in patients with R/R DLBCL and R/R FL who had limited therapeutic options.

In the study, 56 percent of the patients had primary refractory disease and 81 percent of patients were refractory to their last therapy. The median number of prior therapies was three (range: 2 to 8), with 44 percent of patients receiving two prior therapies, 25 percent receiving three prior therapies, and 31 percent receiving four or more prior therapies. Nineteen percent had prior autologous stem cell transplantation (ASCT), no one had prior chimeric antigen receptor (CAR) T-cell therapy.

About the EPCORETM NHL-1 Trial
EPCORE NHL-1 is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab that includes a phase 1 first-in-human, dose escalation part; a phase 2a expansion part; and a dose optimization part. The trial was designed to evaluate subcutaneous epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-cell NHL, including large B-cell lymphoma (LBCL) and DLBCL.iii Data from the dose escalation part of the study, which determined the recommended phase 2 dose, were published in September 2021.iv In the phase 2 expansion part, additional patients were treated with epcoritamab to further explore the safety and efficacy of epcoritamab in three cohorts of patients with different types of relapsed/refractory B-cell NHLs who had limited therapeutic options.iii

The primary endpoint of the phase 2 expansion part was overall response rate as assessed by an independent review committee. Secondary efficacy endpoints included duration of response, complete response rate, progression-free survival, overall survival, time to response, time to next therapy, and rate of minimal residual disease negativity.

About Large B-cell Lymphoma (LBCL)
LBCL is a type of non-Hodgkin’s lymphoma (NHL), a cancer that develops in the lymphatic system, and includes several disease types such as DLBCL, HGBCL, and PMBCL, which are classified as fast-growing, aggressive lymphomas. The total number of patients with NHL, which accounts for more than 90 percent of malignant lymphoma in Japan, is estimated to be approximately 124,000, and DLBCL is reported to account for approximately 30 to 40 percent of NHL.i,ii,iii

About Follicular Lymphoma (FL)
FL is the second most frequent B-cell lymphoma after DLBCL, and accounts for 10 to 20 percent of NHL. Grade 3B disease, which is reported to account for 5 to 10 percent of FL, is treated according to aggressive lymphoma.iv,v

About EPKINLYTM (epcoritamab)
Epcoritamab is an IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology and administered subcutaneously. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response towards target cell types. EPKINLY is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell mediated killing of CD20+ cells.vi

Epcoritamab-bysp (EPKINLYTM) was approved in the United States in May 2023 and is indicated for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma (HGBL) after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes three ongoing phase 3, open-label, randomized trials including a trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL (NCT: 04628494) compared to investigators choice chemotherapy, a phase 3, trial evaluating epcoritamab in combination with R-CHOP in adult participants with newly diagnosed DLBCL (NCT: 05578976), and a phase 3, open-label clinical trial evaluating epcoritamab in combination in patients with R/R follicular lymphoma (FL) (NCT: 05409066). Epcoritamab is not approved to treat newly diagnosed patients with DLBCL or FL. The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit clinicaltrials.gov for more information.

EPKINLY (epcoritamab-bysp) U.S. IMPORTANT SAFETY INFORMATION

Important Warnings—EPKINLY can cause serious side effects, including:

Cytokine Release Syndrome (CRS). CRS is common during treatment with EPKINLY and can be serious or life-threatening. Tell your healthcare provider or get medical help right away if you develop symptoms of CRS, including fever of 100.4°F (38°C) or higher, dizziness or lightheadedness, trouble breathing, chills, fast heartbeat, feeling anxious, headache, confusion, shaking (tremors), or problems with balance and movement, such as trouble walking.

Due to the risk of CRS, you will receive EPKINLY on a "step-up" dosing schedule. The step-up dosing schedule is when you receive smaller "step-up" doses of EPKINLY on day 1 and day 8 of your first cycle of treatment (cycle 1). You will receive your first full dose of EPKINLY on day 15 of cycle 1. If your dose of EPKINLY is delayed for any reason, you may need to repeat the step-up dosing schedule. Before each dose in cycle 1, you will receive medicines to help reduce your risk of CRS. Your healthcare provider will decide if you need to receive medicine to help reduce your risk of CRS with future cycles.

Neurologic problems. EPKINLY can cause serious neurologic problems that can be life-threatening and lead to death. Neurologic problems may happen days or weeks after you receive EPKINLY. Your healthcare provider may refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you develop any symptoms of neurologic problems, including trouble speaking or writing, confusion and disorientation, drowsiness, tiredness or lack of energy, muscle weakness, shaking (tremors), seizures, or memory loss.
Due to the risk of CRS and neurologic problems, you should be hospitalized for 24 hours after receiving your first full dose of EPKINLY on day 15 of cycle 1. Your healthcare provider will monitor you for symptoms of CRS and neurologic problems during treatment with EPKINLY, as well as other side effects, and treat you if needed. Your healthcare provider may temporarily stop or completely stop your treatment with EPKINLY if you develop CRS, neurologic problems, or any other side effects that are severe.

Do not drive or use heavy or potentially dangerous machinery if you develop dizziness, confusion, tremors, drowsiness, or any other symptoms that impair consciousness until your symptoms go away. These may be symptoms of CRS or neurologic problems.

EPKINLY can also cause other serious side effects, including:

Infections. EPKINLY can cause serious infections that may lead to death. Your healthcare provider will check you for symptoms of infection before and during treatment. Tell your healthcare provider right away if you develop any symptoms of infection during treatment, including fever of 100.4°F (38°C) or higher, cough, chest pain, tiredness, shortness of breath, painful rash, sore throat, pain during urination, or feeling weak or generally unwell.
Low blood cell counts. Low blood cell counts are common during treatment with EPKINLY and can be serious or severe. Your healthcare provider will check your blood cell counts during treatment. EPKINLY may cause low blood cell counts, including low white blood cell counts (neutropenia), which can increase your risk for infection; low red blood cell counts (anemia), which can cause tiredness and shortness of breath; and low platelet counts (thrombocytopenia), which can cause bruising or bleeding problems.
Your healthcare provider may temporarily stop or completely stop treatment with EPKINLY if you develop certain side effects.

Before you receive EPKINLY, tell your healthcare provider about all of your medical conditions, including if you:

have an infection.
are pregnant or plan to become pregnant. EPKINLY may harm your unborn baby. Females who are able to become pregnant: Your healthcare provider should do a pregnancy test before you start treatment with EPKINLY. You should use effective birth control (contraception) during treatment and for 4 months after your last dose of EPKINLY. Tell your healthcare provider if you become pregnant or think that you may be pregnant during treatment with EPKINLY.
are breastfeeding or plan to breastfeed. It is not known if EPKINLY passes into your breast milk. Do not breastfeed during treatment with EPKINLY and for 4 months after your last dose of EPKINLY.
Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of EPKINLY include CRS, tiredness, muscle and bone pain, injection site reactions, fever, stomach-area (abdominal) pain, nausea, and diarrhea.

These are not all the possible side effects of EPKINLY. Call your doctor for medical advice about side effects.

You are encouraged to report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch or to Genmab US, Inc. at 1-855-4GENMAB (1-855-443-6622).

Please see the Full Prescribing Information and Medication Guide, including Important Warnings.

On September 25, 2023 Defence Therapeutics Inc. ("Defence" or the "Company"), a Canadian biopharmaceutical company specialized in the development of immune-oncology vaccines and drug delivery technologies, reported that its encapsulation strategy used to generate Accum-mRNA lipid nanoparticles (LNPs) results in an antibody response that is twice as potent as standard mRNA LNPs (Press release, Defence Therapeutics, SEP 25, 2023, View Source;utm_medium=rss&utm_campaign=defences-accum-mrna-lipid-nanoparticles-elicit-antibody-response-2x-stronger-than-standard-mrna-vaccines [SID1234635380]). These results constitute a strong basis for conducting additional tests to optimize Defence’s mRNA vaccine pipeline.

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This in vivo study had two main objectives: testing multiple LNP formulations and comparing their induced immune responses to standard mRNA. All vaccines were delivered as part of a prime-boost vaccination protocol with animal bleeding performed every two weeks over a total period of 4 weeks and antibody titers quantified by ELISA. Amongst the tested groups, one Accum-containing LNP formulation stood-up triggering a higher antibody compared to the remaining groups.

"The use of mRNA vaccines now expanding rapidly into cancer therapeutics will expand exponentially over the next decade due to their established potency and ease of manufacturing. Defence will thus strive in applying its platform of Accum technology in mRNA vaccination opportunities, which will have a great impact on the induced immune responses", says Mr. Plouffe, CEO of Defence Therapeutics.

Defence will design additional studies, currently now being prepared to test different concentrations of the selected LNPs. Once the optimal dosing is identified, a validation study will be conducted in cancer-bearing mice to test their therapeutic potency. In this case, animals will be transplanted with a solid tumor expressing an experimental antigen followed by a prime-boost vaccination administered alone or in combination with immune-checkpoint blockers such as anti-PD-1.

Accum has been tested in various applications including protein- and cell-based vaccination modalities and was discovered to significantly boost their therapeutic potency. Defence is therefore convinced that Accum will increase the stability of mRNA molecules by enhancing structural integrity of the molecule, and augment their bio-accumulation and efficient translation in target cells resulting in a stronger immune-reactivity as shown with its latest LNP vaccination study.

On September 25, 2023 Coherus BioSciences, Inc. ("Coherus", NASDAQ: CHRS), a commercial-stage biopharmaceutical company focused on the research, development, and commercialization of innovative immunotherapies to treat cancer, reported that the U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) regarding the Biologics License Application (BLA) supplement for UDENYCA ONBODY, the company’s on-body injector (OBI) presentation of UDENYCA (pegfilgrastim-cbqv), solely due to an ongoing review of inspection findings at a third-party filler (Press release, Coherus Biosciences, SEP 25, 2023, View Source [SID1234635379]). The CRL did not identify any issues with the UDENYCA ONBODY clinical efficacy or safety, trial design, labeling, drug substance manufacturing, or device design or manufacturing, and no additional data or trials have been requested. Coherus is committed to working closely with the FDA and the third-party filler to bring UDENYCA ONBODY to cancer patients requiring pegfilgrastim treatment as quickly as possible.

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Coherus also announced completion of FDA’s toripalimab inspections
Coherus also announced today that the FDA has completed the clinical study site inspections of three clinical sites in China that enrolled subjects in the two pivotal clinical trials supporting the toripalimab BLA for the treatment of metastatic or recurrent nasopharyngeal carcinoma (NPC) as first-line treatment or as second or greater line treatment. Only one site received an FDA Form 483, with one observation noted. Coherus believes the observation is readily addressable. Coherus continues to anticipate potential approval for toripalimab by year end 2023.

"We are pleased the FDA has completed the review elements for the OBI and toripalimab applications," said Dr. Theresa LaVallee, Coherus Chief Development Officer. "We will work with the third-party filler to address the issues and resubmit the UDENYCA ONBODY application as quickly as possible. Having completed all the required review elements of the toripalimab BLA, we will continue to work collaboratively with the FDA to bring toripalimab, with its substantial improvement in survival compared to chemotherapy, to NPC patients. NPC is a rare cancer with high unmet medical need that has no drugs approved for treatment of this disease in the U.S."