On March 26, 2021 Kintor Pharmaceutical Limited (stock code 9939.HK, "Kintor Pharmaceutical" or the "Company"), a clinical-stage biotechnology company developing small molecule and biological therapeutics, reported its business highlights and financial results for the year ended December 31, 2020 (Press release, Suzhou Kintor Pharmaceuticals, MAR 26, 2021, View Source [SID1234577217]).

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Dr. Youzhi Tong, co-founder, chairman, and CEO of Kintor Pharmaceutical, said, "In 2020, despite the global COVID-19 pandemic and subsequent public health crisis , the Kintor team overcame numerous challenges and continued making breakthroughs in research and development, and progress in clinical operations and commercial collaborations. On May 22, the Company was officially listed on the main board of the Hong Kong Stock Exchange, raising approximately US$240 million, which will support the Company’s long-term goals in developing and commercializing important therapeutics for unmet medical needs.

The Company’s new investigational drug, proxalutamide, has expanded its indication to COVID-19. Clinical research has found that it may be an important tool in treating COVID-19 patients with mild, moderate, severe, and critical symptoms. In an investigator-initiated clinical trial in Brazil, results announced showed that among patients treated with proxalutamide the hospitalization rate of male patients with mild or moderate symptoms was reduced by 100%, while that of female patients was reduced by 90%; the mortality rate of severely-ill patients was reduced by 92%, cutting the length of stay by 9 days.

In addition, the Company collected positive data in a Taiwan-based Phase II clinical trial of the combination therapy of ALK-1 monoclonal antibody and nivolumab to treat metastatic hepatocellular carcinoma (HCC). The trial results showed an objective response rate (ORR) of 40%. The Phase II clinical trial of the combination therapy of ALK-1 monoclonal antibody and nivolumab for the second line therapy of HCC has been approved by the U.S. Food and Drug Administration(FDA), and we are in the process of recruiting patients.

In 2020, the Company established partnerships with six companies. We entered into an exclusive license agreement with the American firm, Gensun for the development and commercialization of the dual-target antibody PD-L1/TGF-β in Greater China. We will be collaborating in the field of monoclonal antibody and bispecific antibody of biological medicine. We also reached a collaboration agreement with Alphamab Oncology to jointly promote the clinical research of ALK-1monoclonal antibody GT90001 combined with recombinant humanized PD-L1/CTLA-4 bispecific antibody KN046 for the treatment of hepatocellular carcinoma andother tumors globally. In August, Kintor Pharmaceutical opened a Good Manufacturing Plant (GMP).

In the face of the COVID-19 pandemic, we at Kintor Pharmaceutical, are deeply aware of the great responsibilities we shoulder. We are gratified to see that proxalutamide is showing great promise in clinical trials for the treatment of COVID-19. The Kintor team has worked on proxalutamide for more than ten years. At the same time, I am pleased that we have received this Phase III clinical trial approval from the FDA. This has been the first Phase III clinical trial approval from the FDA since Kintor’s 2009 founding.

Looking ahead to 2021, Kintor Pharmaceutical will continue its efforts to advance the developmentand commercialization of proxalutamide, as a safe and effective treatment for COVID-19.

In the future, the Company will accelerate the global clinical development of our existing product pipeline, continue to strengthen international and domestic partnerships, and fulfill our mission of "focusing on the research, development and commercialization of a large number of indications with unmet clinical needs." We will continue to work on benefiting more patients and creating long-term value for shareholders. "

Recent Business Progress Highlights

1. Product Pipeline Progress

Currently, the company has six products in clinical development. A number of clinical trials have made important progress:

Proxalutamide (GT0918, AR antagonist), a new generation of AR antagonist

COVID-19 (Brazil and U.S.): In July 2020, the Company signed a clinical trial research agreement with Applied Biology, a U.S. company, to collaborate in the clinical research of proxalutamide for the treatment of COVID-19 in Brazil. On January 7, 2021, the Company announced the final clinical research results of an investigator-initiated trial of proxalutamide in the treatment of male patients with mild and moderate COVID-19 infections. The results of the trial demonstrated the short-term use of proxalutamide is safe and can effectively prevent the deterioration of infection in males from mild to severe COVID-19 infections. In addition, hospitalization rates were reduced by 100%..

On January 10, 2021, data released by the company showed that proxalutamide can significantly inhibit the deterioration of female patients with COVID-19 from mild to severe, and reduce the risk of hospitalization by 90%.

On January 28, 2021, the Brazilian Institutional Review Board approved the clinical trial of proxalutamide in the treatment of severely ill patients with COVID-19 infections and provided support in the allocation of medical resources to further develop the treatment.

On March 11, 2021, the Company announced the results of a clinical study on proxalutamide in the treatment of hospitalized patients with COVID-19 infections. The study results showed the mortality rate of patients treated with proxalutamide was 92% lower than that of the control group, and the length of hospital stay was shortened by 9 days.

On March 4, 2021, the U.S. Food and Drug Administration granted proxalutamide a Phase III clinical trial license for the treatment of patients with mild and moderate COVID-19 infections in the United States. Enrollment of patients will start in second quarter.

Metastatic castration-resistant prostate cancer (China): Two Phase III clinical trials of proxalutamide as a second-line therapy for metastatic castration-resistant prostate cancer (mCRPC) and a combination of proxalutamide and Abiraterone as a first-line therapy are currently underway in China. In February 2021, the Company released the data of the Phase II clinical trial at American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) in respect of the safety and tolerability of Proxalutamide in mCRPC patients who had failed standard chemotherapy (including Docetaxel) or were unable to tolerate or unwilling to receive standard chemotherapy .

The Phase III clinical trial of proxalutamide monotherapy finished recruiting patients on August 4, 2020. We expect to release results later in 2021.

Metastatic castration-resistant prostate cancer (U.S.): On July 16, 2020, the Phase II clinical trial of proxalutamide in the treatment of metastatic castration-resistant prostate completed patient enrollment in the United States. The clinical study results showed that proxalutamide was generally safe and effective on mCRPC patients progressed after the treatment with existing drugs such as enzalutamide and abiraterone. In February 2021, the Company announced the preliminary analysis of the Phase II study at American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium(ASCO GU) in respect of the safety and tolerability of proxalutamide in mCRPC patients who had progressed on either abiraterone(Abi) or enzalutamide(Enza).

AR+ metastatic breast cancer (China): The Company is currently carrying out an open and multi-centre Phase Ic clinical trial to evaluate the safety, pharmacokinetic characteristics and initial efficacy of proxalutamide in combination with exemestane, letrozole and fulvestrant in patients with AR+ metastatic breast cancer.

Expected milestones in 2021

We will continue to advance the clinical development of proxalutamide for the treatment of COVID-19 infection in 2021 .

In addition, we will continue to advance the clinical development and regulatory process of proxalutamide for the treatment of mCRPC as a single agent and in combination with abiraterone in 2021.

Pyrilutamide (KX-826), AR antagonist forexternal use

Androgenetic alopecia (China): On December 29, 2020, the recruitment of patients for the Phase II clinical trial of pyrilutamide in China was completed. On September 17, 2020, the Company’s application of new drug research for pyrilutamide gel formulation for the indication of androgenetic alopecia was approved by the National Medical Products Administration (NMPA).

Androgenetic alopecia (U.S.): In August 2020, the Company completed the Phase Ib clinical trial of pyrilutamide in the U.S. The analysis and evaluation of the trial data are in progress.

Acne (China): On September 17, 2020, the Company’s application of new drug research for the acne indications of the pyrilutamide gel formulation was approved by the National Medical Products Administration (NMPA).

Expected milestones in 2021

The company expects to complete Phase II clinical research report and release data of pyrilutamide in China for androgenetic alopecia in the third quarter of 2021.

In the first half of 2021, data from the Phase Ib clinical research of pyrilutamidein the U.S. for androgenetic alopecia will be completed and released.

In the second quarter of 2021, the Company expects to complete the first enrollment of Phase I clinical trials of acne for pyrilutamide in China. The Phase I clinical trials are expected to be completed in 2021.

ALK-1 (GT90001), a new anti-angiogenesisinhibitor

Metastatic hepatocellular carcinoma (Taiwan): The Company is carrying out Phase II clinical trials of ALK-1 monoclonal antibody and nivolumab (PD-1) in Taiwan, China for the treatment for metastatic hepatocellular carcinoma. In January 2021, the Company announced the Taiwanese clinical trial data of ALK-1 monoclonal antibody and nivolumab combined with second-line treatment of metastatic hepatocellular carcinoma at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium(ASCO GI). The results showed the treatment was safe and that 40% of patients observed partial remission.

Metastatic hepatocellular carcinoma (U.S.): On February 11, 2021, FDA approved GT90001 combined with nivolumab for the second-line treatment for advanced hepatocellular carcinoma in the Phase II clinical trial. Enrollment of patients is currently underway.

Detorsertib (GT0486), PI3K/mTOR signaling pathway inhibitor

Metastatic solid tumor (China): The company obtained an IND approval in the PRC in August 2019. A Phase I clinical trial is currently underway.

Expected milestones in 2021

The Phase I clinical trial of GT20029 in China will be completed in 2021.

GT1708F (Hedgehog/SMOinhibitor), hedgehog signal transduction pathway inhibitor

Leukemia and Basal Cell Carcinoma (China): The company obtained China’s IND approval in February 2020.

Basalcell carcinoma (U.S.): In November 2020, the U.S.FDA accepted the company’s SMO antagonist for clinical trials in the treatment of basal cell carcinoma.

Expected milestones in 2021

The Phase I clinical trial of GT1708F for leukemia in China will be completed in 2021.

GT20029, PROTAC-AR degrader

Androgenetic alopecia and acne (China): In February 2021, the IND application was accepted by the Chinese Center for Drug Evaluation (CDE) for the treatment of androgenetic alopecia and acne. It is the world’s first external AR degradation agent based on PROTAC technology.

Expected milestones in 2021

The Phase I clinical trial of GT20029 in China will be initiated in2021.

In addition to the above clinical-stage drugs, the Company is developing a variety of pre-clinical-stage drugs, including c-Myc inhibitors for the treatment of blood cancer and PD-L1/TGF-β dual target antibodies for the treatment of various solid tumors as well as other indications.

2. Production Base

Suzhou: The Company’s first GMP plant is located at No. 20 Songbei Road, Industrial Park, Suzhou, Jiangsu Province. It covers an area of about 20,000 square meters. It was put into operation in August 2020 for the commercial production of proxalutamide and pyrilutamide. In November 2020, the factory obtained the"Drug Manufacturing License."

Pinghu: The production base for crude drug and preparations in Pinghu, Zhejiang Province, covers an area of 40,000 square meters. The design of the project has been completed, and construction is expected to start in the third quarter of 2021. The construction will be completed before the end of 2022.

3. Commercial Collaboration

Pyrilutamide commercial collaboration:

On 20 June 2020, the Company and Jingdong Healthcare entered into a framework agreement pursuant to which the parties will embark on in-depth collaboration for thesales and marketing of pyrilutamide on the online pharmaceutical retail platform JD.com Pharmacy operated by JD Healthcare.

In March 2020, the Company signed a collaboration agreement with Sinopharm Holding Co., Ltd.,and will carry out all-round collaboration in product design, business channel expansion, terminal services, and other aspects.

Collaboration with Alphamab Oncology

In July 2020, the Company and Alphamab Oncology reached a collaboration agreement to jointly develop the combination therapy of PD-L1/CTLA-4 bispecific antibody KN046 andALK-1 monoclonal antibody GT90001 in HCC globally.

Collaboration with Gensun, US

In August 2020, the Company entered into an exclusive license agreement with an American company, Gensun Biopharma, for the PD-L1/TGF-β dual target antibody GS19, Inc. Kintor Pharmaceutical obtained the exclusive right to carry out clinical development and commercialization with GS19 in the Greater China region.

Collaboration with MabPlex International

In September 2020, the company signed a strategic collaboration agreement with MabPlex International Co., Ltd., and the two parties launched a full range of collaboration on the development and production of bio-macromolecule drugs.

Collaboration with Biotheus

In October 2020, the Company and Biotheus (Zhuhai) Co., Ltd. reached astrategic collaboration agreement on the development of biological drugs.

4. Layout of Globalization

*Establishment of New Beijing Subsidiary: Clinical and Government Affairs

*Establishment of New Guangdong Subsidiary: Macromolecular R&D and Production Base

2020 Annual Financial Performance

As of December 31, 2020, the Company’s research and development costs increased by RMB 114.8 million, up 53.6%, from RMB 214 million for the twelve months ended December 31, 2019 to RMB 328.8 million for the twelve months ended December 31, 2020. The main reason for the increase in R&D expenditure is that the Company continued to increase R&D investment, accelerated the advancement of multiple clinical trials in the product pipeline, increased R&D and clinical operating staff, and the expenditure of equity incentive plans.

As of December 31, 2019, the Company’s cash and cash equivalents amounted to RMB 195.5 million compared with RMB 1389.0 million as of December 31, 2020, representing an increase of RMB 1193.5 million, which was mainly due to the IPO fund-raising and bank loans.

As of December 31, 2020, the Company has used RMB 218.5 million of bank financing, with RMB 101.0 million left.

On March 26, 2021 Boston Scientific Corporation (NYSE: BSX) reported that it will webcast its conference call discussing financial results and business highlights for the first quarter ending March 31, 2021 on Wednesday, April 28, 2021 at 8:00 a.m. EDT (Press release, Boston Scientific, MAR 26, 2021, View Source [SID1234577216]). The call will be hosted by Mike Mahoney, chairman and chief executive officer, and Dan Brennan, executive vice president and chief financial officer. The company will issue a news release announcing financial results for the first quarter on April 28 prior to the conference call.

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On May 5, 2021, Susie Lisa, vice president, Investor Relations and Lauren Tengler, director, Investor Relations will participate in a 40-minute question-and-answer session with the host analyst at the Truist Securities 2021 Life Sciences Summit. The session will begin at approximately 10:30 a.m. EDT.

A live webcast and replay of the webcast for each event will be accessible at investors.bostonscientific.com. The replay will be available beginning approximately one hour following the completion of each event.

On March 26, 2021 Genscript Biotech (HKEX: 1548.HK) (GenScript), a global leading biotech company, reported its audited financial results for the year ended December 31, 2020 (Press release, GenScript, MAR 26, 2021, View Source [SID1234577215]).

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"In 2020, the outbreak of COVID-19 pandemic presented both challenges and opportunities to the life science community. Thanks to concerted efforts of all GenScript people, the Group delivered historically strong results amid the outbreak," said Patrick Liu, Rotating CEO of GenScript. "In the past year, our business segments tided over difficulties, turned challenges into opportunities and achieved many breakthroughs. In the future, we will move forward with dedication and create more value for both our investors and customers. We are committed to our mission of "making people and nature healthier through biotechnology" and strive for human wellbeing."

Financial Results Highlits for the Year Ended December 31, 2020

Revenue

In 2020, the Group recorded revenue of approximately US$390.8 million, representing an increase of 42.9% from approximately US$273.4 million in 2019. This was primarily attributable to (i) the strong growth in business of specially-functioned protein and antibody which meet market demands on key products related to COVID-19, (ii) the continuing increase from life-science services and products from major strategic customers and new competitive services and products, (iii) the increase of contract revenue derived from Legend’s collaboration with Janssen with new milestone achieved, and (iv) the increase in both the number of customers and their purchase volume of industrial synthetic biology products.

Gross Profit

In 2020, the Group’s gross profit increased by 41.9% to approximately US$255.9 million from approximately US$180.3 million in 2019. The increase in gross profit was primarily attributable to the (i) strong growth in life-science and biologics development business and high gross margin products, especially for COVID-19, and (ii) significant improvement on capacity utilization of materials and labor efficiency in industrial synthetic biology products.

Selling and distribution expenses

The selling and distribution expenses increased by 52.4% to approximately US$107.3 million in 2020 from approximately US$70.4 million in 2019. This was mainly attributable to the (i) increased investment into the commercial talent pool by recruiting more experienced personnel and improving incentive packages, and (ii) increased expenses for the global expansion of our business.

Administrative expenses

In 2020, the administrative expenses increased by 63.3% to approximately US$90.3 million from US$55.3 million in 2019. This was mainly caused by (i) competitive compensation package for our employees including shared-based payment provided to recruit experienced talents for all business segments, (ii) the reinforcement of some key administrative functions such as information technology, supply chain and finance to build up capable and professional administrative team to support the Group’s overall business expansion, and (iii) the expansion of the European and Asia- Pacific Regional centers to accelerate the Group’s global market penetration.

Research and development expenses

The research and development expenses increased by 41.6% to approximately US$263.4 million in 2020 from approximately US$186.0 million in 2019. This was mainly due to the (i) investment in COVID-19 related projects and other new challenging research and development projects, which significantly strengthened our competitiveness in the market and improved our production efficiency, (ii) increase in clinical trial expenses and preclinical study costs, especially in the cell therapy segment, and (iii) increase in compensation package including shared-based payment for research and development personnel.

On March 26, 2021 Bristol Myers Squibb (NYSE: BMY) and bluebird bio, Inc. (Nasdaq: BLUE) reported that the U.S. Food and Drug Administration (FDA) has approved Abecma (idecabtagene vicleucel; ide-cel) as the first B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody (Press release, Bristol-Myers Squibb, MAR 26, 2021, View Source [SID1234577212]). Abecma is a personalized immune cell therapy approved as a one-time infusion with a recommended dose range of 300 to 460 x 106 CAR-positive T cells.1 As an anti-BCMA CAR T cell therapy, Abecma recognizes and binds to BCMA, a protein that is nearly universally expressed on cancer cells in multiple myeloma, leading to the death of BCMA-expressing cells.2 Please see the Important Safety Information section below, including Boxed WARNINGS for Abecma regarding Cytokine Release Syndrome (CRS), Neurologic Toxicities (NT), Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), and Prolonged Cytopenia.

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"CAR T cell therapies have shown transformational potential for the treatment of hematologic malignancies, and we, with our partners at bluebird bio, are proud to bring the first CAR T cell therapy to appropriate triple-class exposed patients with relapsed or refractory multiple myeloma, offering the chance for durable response," said Samit Hirawat, M.D., chief medical officer, Bristol Myers Squibb. "Bristol Myers Squibb is now the only company with two approved CAR T cell therapies with distinct targets of CD19 and BCMA. As our second FDA-approved CAR T cell therapy, Abecma underscores our commitment to deliver on the promise of cell therapies for patients who are battling aggressive and advanced blood cancers with limited effective treatment options."

"Our journey to today’s approval of Abecma started nearly a decade ago with pioneering research at bluebird bio and has been driven ever since by our mission to provide patients with multiple myeloma a new approach to fight this relentless disease. This achievement would not have been possible without all of the patients, caregivers, investigators and healthcare staff who participated in our clinical studies, as well as the tremendous collaboration with the FDA," said Nick Leschly, chief bluebird, bluebird bio. "Today’s announcement represents an important milestone for bluebird bio, marking both our first approved treatment in oncology and our first approved treatment in the United States."

Despite advances in treatment, multiple myeloma remains an incurable disease characterized by periods of remission and relapse.3 Most patients experience relapse following initial therapies, and depth and duration of response as well as survival outcomes decrease with each successive treatment.4-9 Patients with relapsed or refractory multiple myeloma that have been exposed to all three major drug classes (triple-class exposed), including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, tend to demonstrate poor clinical outcomes with very low response rates (20% to 30%), short duration of response (2 to 4 months) and poor survival.5,10,11,12

"In the KarMMa study, ide-celelicited rapid responses in the majority of patients, and these deep and durable responses were observed in patients with triple-class exposed and refractory multiple myeloma," said Nikhil C. Munshi, M.D., Associate Director, The Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute, Boston, Massachusetts. "As a treating physician, I often work with patients with relapsed or refractory multiple myeloma who are in critical need of new therapies. Now, with the approval of ide-celas the first anti-BCMA CAR T cell therapy, we are excited to finally be able to offer patients a new, effective personalized treatment option that is delivered through a single infusion."

A network has been created to support rapid and dependable manufacturing of Abecma and ensure capacity to accommodate patient demand. Abecma will be manufactured for each individual patient using the patient’s own T cells at Bristol Myers Squibb’s state-of-the-art cellular immunotherapy manufacturing facility in Summit, New Jersey. The lentiviral vector, which is used to engineer the CAR T cells, was developed by bluebird bio. Abecma patients, caregivers and physician teams can access relevant information, manufacturing updates and patient and caregiver support through Cell Therapy 360, a digital service platform provided to optimize the Abecma patient and physician treatment experience. Various programs and resources will also be offered to help address the needs of patients and caregivers and provide support that allows for access to therapies, including Abecma. Due to the specialized nature of administering cell therapy, Abecma will be available at certified treatment centers throughout the country. A Risk Evaluation and Mitigation Strategy (REMS) program will be implemented at certified centers to support appropriate use of Abecma including training on the management of cytokine release syndrome and neurologic toxicities.

Abecma is being jointly developed and commercialized in the U.S. as part of a Co-Development, Co-Promotion and Profit Share Agreement between Bristol Myers Squibb and bluebird bio.

KarMMa Pivotal Trial Results

The FDA approval of Abecma is based on data from the pivotal Phase II KarMMa trial of 127 patients with relapsed or refractory multiple myeloma who had received at least three prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody. The efficacy evaluable population consists of 100 patients who received Abecma within the dose range of 300 to 460 x 106 CAR-positive T cells. Of these patients, 88% received four or more prior lines of therapy and 85% were triple-class refractory.1

In the study, the overall response rate (ORR) for the efficacy evaluable population (n=100) was 72% (95% CI: 62-81), and 28% of patients achieved a stringent complete response (sCR; 95% CI: 19-38).1 Responses were rapid and durable, with a median time to response of 30 days (range: 15 to 88 days) and median duration of response of 11 months (95% CI: 10.3 – 11.4) for all responders and 19 months (95% CI: 11.4 – NE) for those who achieved sCR. Of the 28 patients who achieved sCR, an estimated 65% (95% CI: 42% – 81%) had remission lasting at least 12 months.1

In patients treated with Abecma in the KarMMa study, the safety profile was well-established with mostly low-grade occurrence of cytokine release syndrome (CRS) and neurotoxicity (NT), and predictable early onset and resolution. CRS of any grade occurred in 85% (108/127) of patients using the Lee grading system.1,13 Grade >3 CRS occurred in 9% (12/127) of patients, with Grade 5 CRS reported in one patient (0.8%). The median time to onset of CRS was one day (range: 1-23 days) and the median duration of CRS was seven days (range: 1-63 days). The most common manifestations of any grade CRS included pyrexia (98%), hypotension (41%), tachycardia (35%), chills (31%), hypoxia (20%), fatigue (12%), and headache (10%). NT of any grade occurred in 28% (36/127) of patients, including Grade ≥3 events in 4% (5/127) of patients. One patient had ongoing Grade 2 NT at the time of death. The median time to onset of NT was two days (range: 1-42 days). NT resolved in 33 of 36 patients (92%) with a median time to resolution of five days (range: 1-61 days). Hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS), potential complications related to excessive immune activation associated with CAR T cell therapies, occurred in 4% (5/127) of patients, including one patient who developed fatal multi-organ HLH/MAS with CRS and one patient with fatal bronchopulmonary aspergillosis, with HLH/MAS contributing to the fatal outcome. Three cases of Grade 2 HLH/MAS resolved. In the study, 41% (52/127) of patients experienced prolonged Grade 3 or 4 neutropenia and 49% (62/127) of patients experienced prolonged Grade 3 or 4 thrombocytopenia. Three patients underwent stem cell transplant for hematopoietic reconstitution due to prolonged cytopenia. Two of the three patients died from complications of prolonged cytopenia, which occurred in the setting of ongoing or prior severe CRS or HLH/MAS.1

The most common (≥20%) types of nonlaboratory adverse reactions included CRS, infections, fatigue, musculoskeletal pain, hypogammaglobulinemia, diarrhea, upper respiratory tract infection, nausea, viral infections, encephalopathy, edema, pyrexia, cough, headache, and decreased appetite. Serious adverse reactions occurred in 67% of patients, with the most common (≥5%) being CRS (18%), general physical health deterioration (10%), pneumonia (12%), infections (19%), viral infections (9%), sepsis (7%), and febrile neutropenia (6%). The most common Grade 3 or 4 nonlaboratory adverse reactions were febrile neutropenia (16%) and infections (14%). Fatal adverse reactions occurred in 6% of patients.1

Indication

ABECMA (idecabtagene vicleucel) is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.

Important Safety Information

BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, AND PROLONGED CYTOPENIA

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with ABECMA. Do not administer ABECMA to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurologic Toxicities, which may be severe or life-threatening, occurred following treatment with ABECMA, including concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with ABECMA. Provide supportive care and/or corticosteroids as needed.
Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS) including fatal and life-threatening reactions, occurred in patients following treatment with ABECMA. HLH/MAS can occur with CRS or neurologic toxicities.
Prolonged Cytopenia with bleeding and infection, including fatal outcomes following stem cell transplantation for hematopoietic recovery, occurred following treatment with ABECMA.
ABECMA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ABECMA REMS.
Cytokine Release Syndrome (CRS): CRS, including fatal or life-threatening reactions, occurred following treatment with ABECMA. CRS occurred in 85% (108/127) of patients receiving ABECMA. Grade 3 or higher CRS (Lee grading system) occurred in 9% (12/127) of patients, with Grade 5 CRS reported in one (0.8%) patient. The median time to onset of CRS, any grade, was 1 day (range: 1 – 23 days) and the median duration of CRS was 7 days (range: 1 – 63 days) in all patients including the patient who died. The most common manifestations of CRS included pyrexia (98%), hypotension (41%), tachycardia (35%), chills (31%), hypoxia (20%), fatigue (12%), and headache (10%). Grade 3 or higher events that may be associated with CRS include hypotension, hypoxia, hyperbilirubinemia, hypofibrinogenemia, acute respiratory distress syndrome (ARDS), atrial fibrillation, hepatocellular injury, metabolic acidosis, pulmonary edema, multiple organ dysfunction syndrome and HLH/MAS.

Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of HLH/MAS, and the physiology of the syndromes may overlap. HLH/MAS is a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS.

Fifty four percent (68/127) of patients received tocilizumab; 35% (45/127) received a single dose while 18% (23/127) received more than 1 dose of tocilizumab. Overall, across the dose levels, 15% (19/127) of patients received at least 1 dose of corticosteroids for treatment of CRS. All patients that received corticosteroids for CRS received tocilizumab.

Overall rate of CRS was 79% and rate of Grade 2 CRS was 23% in patients treated in the 300 x 106 CAR+ T cell dose cohort. For patients treated in the 450 x 106 CAR+ T cell dose cohort, the overall rate of CRS was 96% and rate of Grade 2 CRS was 40%. Rate of Grade 3 or higher CRS was similar across the dose range. The median duration of CRS for the 450 x 106 CAR+ T cell dose cohort was 7 days (range: 1-63 days) and for the 300 x 106 CAR+ T cell dose cohort was 6 days (range: 2-28 days). In the 450 x 106 CAR+ T cell dose cohort, 68% (36/53) of patients received tocilizumab and 23% (12/53) received at least 1 dose of corticosteroids for treatment of CRS. In the 300 x 106 CAR+ T cell dose cohort, 44% (31/70) of patients received tocilizumab and 10% (7/70) received corticosteroids. All patients that received corticosteroids for CRS also received tocilizumab. Ensure that a minimum of 2 doses of tocilizumab are available prior to infusion of ABECMA.

Monitor patients at least daily for 7 days following ABECMA infusion at the REMS-certified healthcare facility for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 4 weeks after infusion. At the first sign of CRS, institute treatment with supportive care, tocilizumab and/or corticosteroids as indicated.

Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time.

Neurologic Toxicities: Neurologic toxicities, which may be severe or life-threatening, occurred following treatment with ABECMA, including concurrently with CRS, after CRS resolution, or in the absence of CRS. CAR T cell-associated neurotoxicity occurred in 28% (36/127) of patients receiving ABECMA, including Grade 3 in 4% (5/127) of patients. One patient had ongoing Grade 2 neurotoxicity at the time of death. Two patients had ongoing Grade 1 tremor at the time of data cutoff. The median time to onset of neurotoxicity was 2 days (range: 1 – 42 days). CAR T cell-associated neurotoxicity resolved in 92% (33/36) of patients with a median duration of neurotoxicity was 5 days (range: 1 – 61 days). The median duration of neurotoxicity was 6 days (range: 1 – 578) in all patients including those with ongoing neurotoxicity at the time of death or data cut off. Thirty-four patients with neurotoxicity had CRS. Neurotoxicity had onset in 3 patients before, 29 patients during, and 2 patients after CRS. The rate of Grade 3 neurotoxicity was 8% in the 450 x 106 CAR+ T cell dose cohort and 1.4% in the 300 x 106 CAR+ T cell dose cohort. The most frequently reported (greater than or equal to 5%) manifestations of CAR T cell-associated neurotoxicity include encephalopathy (20%), tremor (9%), aphasia (7%), and delirium (6%). Grade 4 neurotoxicity and cerebral edema in 1 patient has been reported with ABECMA in another study in multiple myeloma. Grade 3 myelitis and Grade 3 parkinsonism have been reported after treatment with ABECMA in another study in multiple myeloma.

Monitor patients at least daily for 7 days following ABECMA infusion at the REMS-certified healthcare facility for signs and symptoms of neurologic toxicities. Rule out other causes of neurologic symptoms. Monitor patients for signs or symptoms of neurologic toxicities for at least 4 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed.

Counsel patients to seek immediate medical attention should signs or symptoms of neurologic toxicity occur at any time.

Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS): HLH/MAS occurred in 4% (5/127) of patients receiving ABECMA. One patient treated in the 300 x 106 CAR+ T cell dose cohort developed fatal multi-organ HLH/MAS with CRS. In another patient with fatal bronchopulmonary aspergillosis, HLH/MAS was contributory to the fatal outcome. Three cases of Grade 2 HLH/MAS resolved. The rate of HLH/MAS was 8% in the 450 x 106 CAR+ T cell dose cohort and 1% in the 300 x 106 CAR+ T cell dose cohort. All events of HLH/MAS had onset within 10 days of receiving ABECMA with a median onset of 7 days (range: 4-9 days) and occurred in the setting of ongoing or worsening CRS. Two patients with HLH/MAS had overlapping neurotoxicity. The manifestations of HLH/MAS include hypotension, hypoxia, multiple organ dysfunction, renal dysfunction, and cytopenia. HLH/MAS is a potentially life-threatening condition with a high mortality rate if not recognized early and treated. Treatment of HLH/MAS should be administered per institutional standards.

ABECMA REMS: Due to the risk of CRS and neurologic toxicities, ABECMA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ABECMA REMS. Further information is available at www.AbecmaREMS.com or 1‑888‑423‑5436.

Hypersensitivity Reactions: Allergic reactions may occur with the infusion of ABECMA. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO) in ABECMA.

Infections: ABECMA should not be administered to patients with active infections or inflammatory disorders. Severe, life-threatening, or fatal infections occurred in patients after ABECMA infusion. Infections (all grades) occurred in 70% of patients. Grade 3 or 4 infections occurred in 23% of patients. Overall, 4 patients had Grade 5 infections (3%); 2 patients (1.6%) had Grade 5 events of pneumonia, 1 patient (0.8%) had Grade 5 bronchopulmonary aspergillosis, and 1 patient (0.8%) had cytomegalovirus (CMV) pneumonia associated with Pneumocystis jirovecii. Monitor patients for signs and symptoms of infection before and after ABECMA infusion and treat appropriately. Administer prophylactic, preemptive, and/or therapeutic antimicrobials according to standard institutional guidelines.

Febrile neutropenia was observed in 16% (20/127) of patients after ABECMA 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.

Viral Reactivation: Cytomegalovirus (CMV) infection resulting in pneumonia and death has occurred following ABECMA administration. Monitor and treat for CMV reactivation in accordance with clinical guidelines. 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 plasma cells. Perform screening for CMV, HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) in accordance with clinical guidelines before collection of cells for manufacturing.

Prolonged Cytopenias: Patients may exhibit prolonged cytopenias following lymphodepleting chemotherapy and ABECMA infusion. In the KarMMa study, 41% of patients (52/127) experienced prolonged Grade 3 or 4 neutropenia and 49% (62/127) experienced prolonged Grade 3 or 4 thrombocytopenia that had not resolved by Month 1 following ABECMA infusion. Rate of prolonged neutropenia was 49% in the 450 x 106 CAR+ T cell dose cohort and 34% in the 300 x 106 CAR+ T cell dose cohort. In 83% (43/52) of patients who recovered from Grade 3 or 4 neutropenia after Month 1, the median time to recovery from ABECMA infusion was 1.9 months. In 65% (40/62) of patients who recovered from Grade 3 or 4 thrombocytopenia, the median time to recovery was 2.1 months. Median time to cytopenia recovery was similar across the 300 and 450 x 106 dose cohort.

Three patients underwent stem cell therapy for hematopoietic reconstitution due to prolonged cytopenia. Two of the three patients died from complications of prolonged cytopenia. Monitor blood counts prior to and after ABECMA infusion. Manage cytopenia with myeloid growth factor and blood product transfusion support according to institutional guidelines.

Hypogammaglobulinemia: Plasma cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with ABECMA. Hypogammaglobulinemia was reported as an adverse event in 21% (27/127) of patients; laboratory IgG levels fell below 500 mg/dl after infusion in 25% (32/127) of patients treated with ABECMA.

Monitor immunoglobulin levels after treatment with ABECMA and administer IVIG for IgG <400 mg/dl. Manage per local institutional guidelines, including infection precautions and antibiotic or antiviral prophylaxis.

The safety of immunization with live viral vaccines during or following ABECMA 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 ABECMA treatment, and until immune recovery following treatment with ABECMA.

Secondary Malignancies: Patients treated with ABECMA may develop secondary malignancies. Monitor life-long for secondary malignancies. If a secondary malignancy occurs, contact Bristol Myers Squibb at 1-888-805-4555 to obtain instructions on patient samples to collect for testing of secondary malignancy of T cell origin.

Effects on Ability to Drive and Operate Machinery: Due to the potential for neurologic events, including altered mental status or seizures, patients receiving ABECMA are at risk for altered or decreased consciousness or coordination in the 8 weeks following ABECMA infusion. 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: The most common nonlaboratory adverse reactions (incidence greater than or equal to 20%) include CRS, infections – pathogen unspecified, fatigue, musculoskeletal pain, hypogammaglobulinemia, diarrhea, upper respiratory tract infection, nausea, viral infections, encephalopathy, edema, pyrexia, cough, headache, and decreased appetite.

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.

On March 26, 2021 Spectrum Pharmaceuticals (NasdaqGS: SPPI) a biopharmaceutical company focused on novel and targeted oncology therapies, reported it will host a conference call to discuss the fourth quarter and full year 2020 financial results and provide a corporate update on Tuesday, March 30, 2021 at 4:30 p.m. Eastern/1:30 p.m. Pacific (Press release, Spectrum Pharmaceuticals, MAR 26, 2021, View Source [SID1234577211]).

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