On March 27, 2022 Innovent Biologics, Inc. ("Innovent", HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, and Eli Lilly and Company ("Lilly",NYSE: LLY) reported that in light of both parties’ shared commitment to continue bringing innovative medicines to benefit Chinese patients and to leverage the strengths of each party in a win-win manner, parties will now expand the strategic partnership through (Press release, Innovent Biologics, MAR 27, 2022, View Source [SID1234611017]):

i) an agreement for Innovent to obtain the sole commercialization rights to import, market, promote, distribute and detail Cyramza (ramucirumab) and Retsevmo (selpercatinib) once approved in Mainland China, and
ii) a right of first negotiation granted to Innovent for potential future commercialization of Pirtobrutinib in Mainland China.

Cyramza (ramucirumab) was the first U.S. Food and Drug Administration (FDA) approved treatment for patients with advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma with disease progression on or after prior chemotherapy and the first FDA approved biomarker-driven therapy in patients with advanced hepatocellular carcinoma (HCC). In China, Cyramza (ramucirumab) in combination with paclitaxel was approved by National Medical Products Administration (NMPA) for second-line treatment in patients with advanced or metastatic GEJ adenocarcinoma in March 2022, making it the first and only drug approved for the second-line treatment of advanced gastric cancer in China. The New Drug Application (NDA) for Cyramza (ramucirumab) as second-line treatment in patients with HCC with baseline alpha-fetoprotein (AFP) ≥400ng/mL following first-line sorafenib was accepted by NMPA in September 2021. Gastric cancer and liver cancer are the third and fifth largest cancers in terms of incidence with a total of approximately 900,000 new cases yearly in China. Most of the patients experience disease progression on or after first-line treatment. There is an unmet medical need for new treatment options to improve outcomes in these patients.

Retsevmo (selpercatinib) is a highly selective and potent rearranged during transfection (RET) inhibitor. It was approved by FDA, under the brand name Retevmo, as the first therapy specifically indicated for the treatment of adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC), adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, and adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). In China, the NDA for Retsevmo (selpercatinib) for the above indications was accepted by NMPA and granted priority review in August 2021.

According to the agreement, Innovent has the sole commercialization rights for both Cyramza and Retsevmo, once approved in China, of which Innovent will be fully responsible for the pricing, importation, marketing, distribution and detailing of these two products. With a further expanded oncology product portfolio, Innovent intends to use its experienced oncology commercial team to leverage its broad commercial coverage in hospitals and pharmacies at various tiers to make these novel treatment options available to cancer patients in China.

In addition, Lilly has granted a right of first negotiation to Innovent for the potential future commercialization of pirtobrutinib in China. Pirtobrutinib is an investigational, oral, highly selective, non-covalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor being studied globally for the treatment of patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL).

Under the terms of the agreement, upon regulatory approvals of Cyramza in the hepatocellular carcinoma indication and Retsevmo in the non-small lung cancer indication, Innovent will make payments of US$45 million in total and then intends to commercialize Cyramza and Retsevmo in China.

Dr. Michael Yu, Founder, Chairman and CEO of Innovent, stated, "With our long-term strategic partnership with Lilly as a strong foundation, we are excited to further expand our productive relationship through this agreement. Innovent has built up a robust oncology pipeline of over 20 clinical stage assets, an industry-leading medical operations and regulatory affairs team, a broad commercial channel and a professional commercial team of about 3,000 people. Lilly and Innovent have jointly launched and marketed TYVYT (sintilimab) and HALPRYZA (rituximab biosimilar) successfully in China. The addition of Cyramza and Retsevmo, two potential differentiated products, will potentially further expand our oncology portfolio to seven commercialized products by this year, enabling us to provide integrated patient solutions with strong portfolio synergies while enhancing our franchise in large cancer indications including NSCLC, GC and HCC, and potentially in hematological malignancies as well. With Innovent and Lilly’s joint commitment and effort, we hope to make these new treatment options available to benefit more cancer patients in China as soon as possible."

Julio Gay-Ger, President and General Manager of Lilly China, said, "We are very proud of this agreement with Innovent, which is a key long-term strategic partner in China. Oncology is one of Lilly’s core therapeutic areas globally, in which the partnership between the two parties has seen rich fruits in the past several years. We are very confident that through this agreement, Innovent can bring forward Lilly’s innovative medicines to potentially be able to benefit Chinese patients with gastric cancer and lung cancer, helping them live better lives and help realize the ‘Healthy China 2030’goals."

On March 27, 2022 Ascletis Pharma Inc. (HKEX:1672) reported that the latest preclinical research results of the company’s two novel anti-cancer drug candidates, ASC61, an oral PD-L1 inhibitor and ASC60, an oral fatty acid synthase (FASN) inhibitor have been selected for presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 (the "2022 AACR (Free AACR Whitepaper) Annual Meeting"), and the abstracts have already been published on AACR (Free AACR Whitepaper)’s official website (Press release, Ascletis, MAR 27, 2022, View Source [SID1234611019]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The AACR (Free AACR Whitepaper) annual meeting is one of the world’s largest and long-standing scientific gatherings in the field of cancer research. Covering some of the most cutting-edge advances in all areas of oncology research and innovation, the annual event attracts tremendous interest from the global cancer research community. The AACR (Free AACR Whitepaper) annual meeting for this year will be held in New Orleans, Louisiana on April 8 to 13, 2022 CDT.

The abstracts selected for poster presentations at the 2022 AACR (Free AACR Whitepaper) Annual Meeting are as follows:

（1） ASC61

Abstract Title: In vivo efficacy evaluation of ASC61, an oral PD-L1 inhibitor, in two tumor mouse models

Presentation Type: Poster Presentation
Abstract Number: 5529
Session Category: Immunology
Session Title: Preclinical Immunotherapy
Presentation time: April 8, 2022, 12:00PM – 1:00 PM CDT
Presenter/Authors: Jinzi J. Wu, Handan He. Ascletis BioScience Co., Ltd.
ASC61 is an oral potent and highly selective PD-L1 small molecule inhibitor and blocks PD-1/PD-L1 interaction through inducing PD-L1 dimerization and internalization. Preclinical studies showed that ASC61 demonstrated significant antitumor efficacies and were well-tolerated in both syngeneic and humanized tumor mouse models. ASC61 was found to have favorably comparable antitumor activities as the U.S. Food and Drug Administration (FDA) approved PD-L1 therapeutic monoclonal antibody (mAb), Atezolizumab. The Phase I study of ASC61 in advanced solid tumors has received the U.S. IND approval by FDA, and the first patient is planned to be enrolled in the second quarter of 2022.

（2） ASC60

Abstract Title: Efficacy of ASC60, an oral fatty acid synthase inhibitor, in two tumor mouse models

Presentation Type: Poster Presentation
Abstract Number: 5466
Session Category: Experimental and Molecular Therapeutics
Session Title: Small Molecule Therapeutic Agents
Presentation time: April 8, 2022, 12:00PM – 1:00 PM CDT
Presenter/Authors: Jinzi J. Wu, Handan He. Ascletis BioScience Co., Ltd.
ASC60 is a potent, selective and safe oral small molecule inhibitor of FASN. ASC60 can disrupt metabolism and tumor-associated signal transduction in tumor cells through inhibition of de novo lipogenesis (DNL). Preclinical studies showed that ASC60 could suppress tumor growth and enhance the antitumor activities of mPD-1 antibody in tumor mouse models. The application of the Phase I study of ASC60 in patients with advanced solid tumors has been submitted to the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China (NMPA).

"It is our great pleasure to have the research results of our drug candidates selected by the AACR (Free AACR Whitepaper) annual meeting," said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis. "ASC61, an oral PD-L1 inhibitor, and ASC60, an oral FASN inhibitor, have better patient compliance and are easier to be combined with other oral anti-tumor drugs. These studies deepened our understanding of our drug candidates’ mechanism of actions and anti-tumor activities in animal models as well as advanced our clinical development of Company’s oncology pipelines. As we are advancing the Phase III clinical trial of ASC40, another FASN inhibitor, in combination with Bevacizumab for the treatment of recurrent glioblastoma (rGBM), we are exploring opportunities for all-oral combinations between ASC61 and ASC40 (or ASC60) as well as other oral anti-tumor drugs from our business partners."

On March 25, 2022 Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, reported upcoming presentations on two of its skin cancer gene expression profile (GEP) tests at the 2022 American Academy of Dermatology (AAD) Annual Meeting, being held in Boston, March 25-29, 2022 (Press release, Castle Biosciences, MAR 25, 2022, View Source [SID1234611003]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are pleased to once again have the opportunity to share data supporting the value of our tests in the management of patients with skin cancer," said Derek Maetzold, president and chief executive officer of Castle Biosciences. "Our data presentations at AAD highlight two of our proprietary GEP tests, DecisionDx-Melanoma and DecisionDx-SCC, and their ability to independently risk-stratify patients with melanoma or high-risk squamous cell carcinoma, respectively, to potentially guide better informed and more risk-aligned patient care."

DecisionDx-Melanoma

Title: "The 31-gene expression profile stratifies recurrence and metastasis risk in patients with cutaneous melanoma"
Poster number: 32344
Presenter: Abel Jarell, M.D., Northeast Dermatology Associates, P.C., Portsmouth, N.H.
Date: Saturday, March 26, 2022
Location: Poster Presentation Center 2 in the Exhibit Hall
Time: 3:30-3:35 p.m. Eastern time

DecisionDx-Melanoma is Castle’s 31-GEP test designed to use a patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as risk of sentinel lymph node positivity, independent of traditional staging factors. The test classifies a patient’s tumor as low risk of recurrence/metastasis (Class 1A), increased risk (Class 1B/2A) or high risk (Class 2B).

Consistent with previous studies, the poster reports that DecisionDx-Melanoma significantly stratified patients according to their metastatic risk (RFS, DMFS and MSS p<0.001). Further, the poster data demonstrates DecisionDx-Melanoma’s potential to guide patient care as a significant, independent predictor of metastatic recurrence compared to staging using the American Joint Committee on Cancer Staging Manual Eighth Edition (AJCC8) framework (high-risk Class 2B result: hazard ratio 5.38, p=0.014). Moreover, a high-risk Class 2B DecisionDx-Melanoma test result in Stage I and II patients (classified according to AJCC8 staging) was associated with lower patient survival (DMFS and MSS) than that of Stage III patients, showing that the DecisionDx-Melanoma test result provides additional risk information as a complement to existing melanoma management plans.

Additionally, combining a patient’s DecisionDx-Melanoma test result (specifically, a low-risk Class 1A test result) with sentinel lymph node (SLN) status, a commonly used prognostic indicator, was associated with improved recurrence outcomes compared to relying on a negative or positive SLN status alone (recurrence free was 98.0% for Class 1A/SLN negative vs. 93.8% for SLN negative alone, and 100% for Class 1A/SLN positive vs. 80.4% for SLN positive alone). Similar improvements in recurrence accuracy were observed in the high-risk Class 2B DecisionDx-Melanoma test result (recurrence free was 84.6% for Class 2B/SLN negative vs. 93.8% for SLN negative alone and 73.3% for Class 2B/SLN positive vs 80.4% for SLN positive alone). The results of the study provide further support for the ability of DecisionDx-Melanoma to provide independent risk-stratification to determine the likelihood that a patient’s cancer will spread or recur, as well as complement other risk assessment methods, to guide more precise and personalized patient care.

DecisionDx-SCC

Title: "Clinical usage data demonstrates appropriate utilization of the prognostic 40-gene expression profile (40-GEP) test for cutaneous squamous cell carcinoma with one or more risk factors"
Poster number: 35334
Presenter: Aaron S. Farberg, M.D., Baylor Scott & White Health System, Dallas
Date: Sunday, March 27, 2022
Location: Poster Presentation Center 1 in the Exhibit Hall
Time: 9:30-9:35 a.m. Eastern time

DecisionDx-SCC is Castle’s prognostic 40-GEP test designed to use a patient’s tumor biology to predict individual risk of metastasis for patients diagnosed with cutaneous squamous cell carcinoma (SCC) who have one or more high-risk factors. The test stratifies patients into one of three classes based on their biologic risk of metastasis: Class 1 (low risk), Class 2A (moderate risk) or Class 2B (high risk).

Clinical validity and utility of the DecisionDx-SCC test has been reported. Results of those studies indicate that the information provided by the test can improve stratification of high-risk SCC patients and, if incorporated into clinical assessments with any number of traditional clinicopathologic risk factors, could assist physicians in guiding more risk-appropriate surveillance and treatment decisions.

DecisionDx-SCC is validated for use in patients with high-risk SCC, defined as the presence of one or more clinicopathologic risk factors, and clinical data has demonstrated its ability to accurately and independently stratify patients according to their biologic risk of metastasis. Analysis of one year of real-world clinical data (2,503 DecisionDx-SCC test orders received between Aug. 31, 2020-Aug. 31, 2021) showed that the intended use population (high-risk SCC patients) aligns with the cases submitted for testing, indicating that physicians understand the appropriate use criteria for the test. Of note, within this high-risk population, nearly 70% of patients received a DecisionDx-SCC Class 1 test result, signifying that they have a biologically lower risk for metastasis. Overall, the current study data, combined with the presented previous validation data, indicates that the testing population aligns with a high-risk population.

About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as risk of sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 6,000 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in four archival risk of recurrence studies of 901 patients and six prospective risk of recurrence studies including more than 1,600 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results. To predict risk of recurrence and likelihood of sentinel lymph node positivity, the Company utilizes its proprietary algorithms, i31-ROR and i31-SLNB, to produce an Integrated Test Result. Through Dec. 31, 2021, DecisionDx-Melanoma has been ordered 90,154 times for use with patients with cutaneous melanoma.

About DecisionDx-SCC

DecisionDx-SCC is a 40-gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous squamous cell carcinoma metastasis for patients with one or more risk factors. The test result, in which patients are stratified into a Class 1 (low), 2A (moderate) or 2B (high) risk category, predicts individual metastatic risk to inform risk-appropriate management.

Peer-reviewed publications have demonstrated that DecisionDx-SCC is an independent predictor of metastatic risk and that integrating DecisionDx-SCC with current prognostic methods can add positive predictive value to clinician decisions regarding staging and management.

More information about the Castle tests can be found at www.CastleTestInfo.com.

On March 25, 2022 Bristol-Myers Squibb K.K. reported that the Ministry of Health, Labour and Welfare (MHLW) has accepted the supplemental New Drug Application for Breyanzi (lisocabtagene maraleucel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy for the second-line treatment of patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) (Press release, Bristol-Myers Squibb, MAR 25, 2022, View Source [SID1234610988]). This is the first CAR T cell therapy application filed for the second-line treatment of R/R LBCL in Japan.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The acceptance is based on the efficacy and safety data yielded by the TRANSFORM study in patients with R/R aggressive B-cell non-Hodgkin lymphoma conducted in Japan, the U.S. and the EU, and other studies.

LBCL comprises several disease types including diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common form of non-Hodgkin lymphoma in Japan, accounting for 30-40% of all B-cell cases diagnosed,1 and is especially prevalent among those in their 60s.2 There are currently no established standard-of-care treatment options for patients with R/R LBCL,3 which underscores the need for new treatments for this disease.

Makoto Sugita, Vice President, R&D Japan, Bristol-Myers Squibb K.K., commented, "I am pleased we are the first company in Japan to file an application for a cell therapy in second-line relapsed or refractory large B-cell lymphoma. This filing brings us one step closer to delivering a potentially practice-changing treatment for primary relapsed or refractory large B-cell lymphoma, making Breyanzi available to more patients in need, and underscores the advancements we’re making in cell therapy research to transform the lives of patients with difficult-to-treat blood cancers, including lymphoma."

Breyanzi is a CD19-directed CAR T cell therapy with a defined composition and 4-1BB costimulatory domain. Breyanzi is administered as a defined composition to reduce variability of the CD8 and CD4 component dose. The 4-1BB signaling domain enhances the expansion and persistence of the CAR T cells. Breyanzi has been designated as an orphan regenerative medicine product by the MHLW for aggressive B-cell non-Hodgkin lymphoma, and was approved in March 2021 for the treatment of patients with R/R LBCL and R/R follicular lymphoma. 4,5

Breyanzi U.S. FDA-Approved Indication

BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B.

Limitations of Use: BREYANZI is not indicated for the treatment of patients with primary central nervous system lymphoma.

U.S. Important Safety Information

BOXED WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving BREYANZI. Do not administer BREYANZI to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab with or without corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving BREYANZI, including concurrently with CRS, after CRS resolution or in the absence of CRS. Monitor for neurologic events after treatment with BREYANZI. Provide supportive care and/or corticosteroids as needed.
BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS.
Cytokine Release Syndrome (CRS)

CRS, including fatal or life-threatening reactions, occurred following treatment with BREYANZI. CRS occurred in 46% (122/268) of patients receiving BREYANZI, including ≥ Grade 3 (Lee grading system) CRS in 4% (11/268) of patients. One patient had fatal CRS and 2 had ongoing CRS at time of death. The median time to onset was 5 days (range: 1 to 15 days). CRS resolved in 119 of 122 patients (98%) with a median duration of 5 days (range: 1 to 17 days). Median duration of CRS was 5 days (range 1 to 30 days) in all patients, including those who died or had CRS ongoing at time of death.

Among patients with CRS, the most common manifestations of CRS include fever (93%), hypotension (49%), tachycardia (39%), chills (28%), and hypoxia (21%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, diffuse alveolar damage, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).

Ensure that 2 doses of tocilizumab are available prior to infusion of BREYANZI.

Sixty-one of 268 (23%) patients received tocilizumab and/or a corticosteroid for CRS after infusion of BREYANZI. Twenty-seven (10%) patients received tocilizumab only, 25 (9%) received tocilizumab and a corticosteroid, and 9 (3%) received corticosteroids only.

Neurologic Toxicities

Neurologic toxicities that were fatal or life-threatening, occurred following treatment with BREYANZI. CAR T cell-associated neurologic toxicities occurred in 35% (95/268) of patients receiving BREYANZI, including ≥ Grade 3 in 12% (31/268) of patients. Three patients had fatal neurologic toxicity and 7 had ongoing neurologic toxicity at time of death. The median time to onset of the first event was 8 days (range: 1 to 46 days). The onset of all neurologic events occurred within the first 8 weeks following BREYANZI infusion. Neurologic toxicities resolved in 81 of 95 patients (85%) with a median duration of 12 days (range: 1 to 87 days). Three of four patients with ongoing neurologic toxicity at data cutoff had tremor and one subject had encephalopathy. Median duration of neurologic toxicity was 15 days (range: 1 to 785 days) in all patients, including those with ongoing neurologic events at the time of death or at data cutoff.

Seventy-eight (78) of 95 (82%) patients with neurologic toxicity experienced CRS. Neurologic toxicity overlapped with CRS in 57 patients. The onset of neurologic toxicity was after onset of CRS in 30 patients, before CRS onset in 13 patients, same day as CRS onset in 7 patients, and same day as CRS resolution in 7 patients.

Neurologic toxicity resolved in three patients before the onset of CRS. Eighteen patients experienced neurologic toxicity after resolution of CRS.

The most common neurologic toxicities included encephalopathy (24%), tremor (14%), aphasia (9%), delirium (7%), headache (7%), dizziness (6%), and ataxia (6%). Serious events including cerebral edema and seizures occurred with BREYANZI. Fatal and serious cases of leukoencephalopathy, some attributable to fludarabine, have occurred in patients treated with BREYANZI.

CRS and Neurologic Toxicities Monitoring

Monitor patients daily at a certified healthcare facility during the first week following infusion, for signs and symptoms of CRS and neurologic toxicities. Monitor patients for signs and symptoms of CRS and neurologic toxicities for at least 4 weeks after infusion; evaluate and treat promptly. Counsel patients to seek immediate medical attention should signs or symptoms of CRS or neurologic toxicity occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.

BREYANZI REMS

Because of the risk of CRS and neurologic toxicities, BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS. The required components of the BREYANZI REMS are:

Healthcare facilities that dispense and administer BREYANZI must be enrolled and comply with the REMS requirements.
Certified healthcare facilities must have on-site, immediate access to tocilizumab.
Ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after BREYANZI infusion, if needed for treatment of CRS.
Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer BREYANZI are trained on the management of CRS and neurologic toxicities.
Further information is available at www.BreyanziREMS.com or contact Bristol Myers Squibb at 1-888-423-5436.

Hypersensitivity Reactions

Allergic reactions may occur with the infusion of BREYANZI. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO).

Serious Infections

Severe infections, including life-threatening or fatal infections, have occurred in patients after BREYANZI infusion. Infections (all grades) occurred in 45% (121/268) of patients. Grade 3 or higher infections occurred in 19% of patients. Grade 3 or higher infections with an unspecified pathogen occurred in 16% of patients, bacterial infections occurred in 5%, and viral and fungal infections occurred in 1.5% and 0.4% of patients, respectively. Monitor patients for signs and symptoms of infection before and after BREYANZI administration and treat appropriately. Administer prophylactic antimicrobials according to standard institutional guidelines.

Febrile neutropenia has been observed in 9% (24/268) of patients after BREYANZI infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated.

Avoid administration of BREYANZI in patients with clinically significant active systemic infections.

Viral reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells. Ten of the 11 patients in the TRANSCEND study with a prior history of HBV were treated with concurrent antiviral suppressive therapy to prevent HBV reactivation during and after treatment with BREYANZI. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

Prolonged Cytopenias

Patients may exhibit cytopenias not resolved for several weeks following lymphodepleting chemotherapy and BREYANZI infusion. Grade 3 or higher cytopenias persisted at Day 29 following BREYANZI infusion in 31% (84/268) of patients, and included thrombocytopenia (26%), neutropenia (14%), and anemia (3%). Monitor complete blood counts prior to and after BREYANZI administration.

Hypogammaglobulinemia

B-cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with BREYANZI. The adverse event of hypogammaglobulinemia was reported as an adverse reaction in 14% (37/268) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 21% (56/268) of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion, was reported in 32% (85/268) of patients. Monitor immunoglobulin levels after treatment with BREYANZI and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement as clinically indicated.

Live vaccines: The safety of immunization with live viral vaccines during or following BREYANZI treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during BREYANZI treatment, and until immune recovery following treatment with BREYANZI.

Secondary Malignancies

Patients treated with BREYANZI may develop secondary malignancies. Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Bristol Myers Squibb at 1-888-805-4555 for reporting and to obtain instructions on collection of patient samples for testing.

Effects on Ability to Drive and Use Machines

Due to the potential for neurologic events, including altered mental status or seizures, patients receiving BREYANZI are at risk for altered or decreased consciousness or impaired coordination in the 8 weeks following BREYANZI administration. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

Adverse Reactions

Serious adverse reactions occurred in 46% of patients. The most common nonlaboratory, serious adverse reactions (> 2%) were CRS, encephalopathy, sepsis, febrile neutropenia, aphasia, pneumonia, fever, hypotension, dizziness, and delirium. Fatal adverse reactions occurred in 4% of patients.

The most common nonlaboratory adverse reactions of any grade (≥ 20%) were fatigue, CRS, musculoskeletal pain, nausea, headache, encephalopathy, infections (pathogen unspecified), decreased appetite, diarrhea, hypotension, tachycardia, dizziness, cough, constipation, abdominal pain, vomiting, and edema.

Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future. Learn more about the science behind cell therapy and ongoing research at Bristol Myers Squibb here.

On March 25, 2022 The Janssen Pharmaceutical Companies of Johnson & Johnson reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended marketing authorisation of ciltacabtagene autoleucel (cilta-cel) for the treatment of adults with relapsed and refractory multiple myeloma, who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody and have demonstrated disease progression on the last therapy (Press release, Johnson & Johnson, MAR 25, 2022, View Source [SID1234611004]). In December 2017, Janssen Biotech, Inc. (Janssen) entered into an exclusive worldwide license and collaboration agreement with Legend Biotech USA, Inc. to develop and commercialise cilta-cel.1

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Cilta-cel is a chimeric antigen receptor T-cell (CAR-T) therapy featuring two B-cell maturation antigen (BCMA)-targeting single domain antibodies.2 CAR-T therapy is a highly personalised technology where a patient’s own T-cells are re-programmed to target and kill cancer cells – and is administered as a single infusion.3

Multiple myeloma is an incurable blood cancer, with around 50 percent of newly diagnosed patients not reaching five-year survival.4,5 Despite the development of additional treatment options in recent years, most people living with multiple myeloma face poor prognoses after being exposed to all three major drug classes, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody.6

"Although significant advances have been made in the treatment of multiple myeloma, it remains a heterogenous disease that is challenging to treat," said Edmond Chan MBChB M.D. (Res), EMEA Therapeutic Area Lead Haematology, Janssen-Cilag Limited. "Therapeutic innovations with novel mechanisms of action are urgently needed. Our focus is on bringing transformative treatments to the medical community, like cilta-cel, for patients with multiple myeloma in need of new options."

The positive CHMP Opinion is supported by data from the pivotal CARTITUDE-1 study. Results from the study were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2021 Annual Meeting (Abstract #549).2

"At Janssen, we are resolute in our commitment to advance science and improve outcomes for patients diagnosed with multiple myeloma," said Sen Zhuang, M.D., Ph.D., Vice President, Oncology Clinical Research, Janssen Research & Development, LLC. "Today’s CHMP positive opinion marks important progress in the ongoing clinical development and registration of cilta-cel, globally."

This CHMP Opinion follows the recent approval of cilta-cel by the United States (U.S.) Food and Drug Administration (FDA) in February 2022.

#ENDS#

About Ciltacabtagene Autoleucel (cilta-cel)
Cilta-cel is a B-cell maturation antigen (BCMA)-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient’s own T-cells with a transgene encoding a chimeric antigen receptor (CAR) that identifies and eliminates cells that express BCMA.2,3 BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B-cells and plasma cells.7,8 The cilta-cel CAR protein features two BCMA-targeting single domain antibodies designed to confer high avidity against human BCMA. 1 Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.9

In December 2017, Janssen Biotech, Inc. (Janssen) entered into an exclusive worldwide license and collaboration agreement with Legend Biotech to develop and commercialise cilta-cel.1

In April 2021, Janssen announced its submission of a Marketing Authorisation Application to the European Medicines Agency seeking approval of cilta-cel for the treatment of patients with relapsed and/or refractory multiple myeloma. In addition to United States (U.S.) Breakthrough Therapy Designation granted in December 2019, cilta-cel received a PRIority MEdicines (PRiME) designation from the European Commission (EC) in April 2019, and a Breakthrough Therapy Designation in China in August 2020. Janssen also received Orphan Drug Designation for cilta-cel from the EC in February 2020 and from the Pharmaceuticals and Medicinal Devices Agency (PMDA) in Japan in June 2020.

About Multiple Myeloma
Multiple myeloma is currently an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.4,10 When damaged, these plasma cells change and grow out of control.10 In Europe, more than 50,900 people were diagnosed with multiple myeloma in 2020, and more than 32,500 patients died.11 While some patients with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels or kidney failure.12