On December 29, 2021 The Janssen Pharmaceutical Companies of Johnson & Johnson reported the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) seeking approval of teclistamab for the treatment of patients with relapsed or refractory (R/R) multiple myeloma (Press release, Johnson & Johnson, DEC 29, 2021, View Source [SID1234597842]). Teclistamab is an investigational, off-the-shelf, T-cell redirecting, bispecific antibody targeting both B-cell maturation antigen (BCMA) and CD3.

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"Despite all the gains that have been made in treating multiple myeloma, the unmet need still remains very high. Our relentless pursuit of treatments for this disease continues with the same sense of urgency that we have always had," said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. "We look forward to working with the FDA in their review of our teclistamab submission."

The BLA submission for teclistamab is supported by data from MajesTEC-1 (NCT04557098, NCT03145181), an open-label, multicenter clinical trial evaluating the safety and efficacy of teclistamab in adults with R/R multiple myeloma. In the study, investigators assessed efficacy outcomes, including overall response rate, very good partial response and complete response using International Myeloma Working Group (IMWG) criteria, as well as the safety profile of teclistamab. Updated MajesTEC-1 data were recently presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting.1

"The deep expertise, creativity and persistence of the entire Janssen R&D organization enabled the expeditious advancement of teclistamab for multiple myeloma," said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, Johnson & Johnson. "Today’s submission is another important step in our commitment to bring to patients truly transformational medicines that profoundly impact their health."

Multiple myeloma is an incurable blood cancer that affects white blood cells called plasma cells, which are found in the bone marrow and normally make antibodies which fight infection.2,3 When these plasma cells become malignant and develop into multiple myeloma, these myeloma cells proliferate and replace normal cells in the bone marrow. In 2021, it is estimated that nearly 35,000 people will be diagnosed and more than 12,000 will die from this disease in the U.S.4 While some patients with multiple myeloma initially have no symptoms, many patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.5

About Teclistamab
Teclistamab is an investigational, off-the-shelf, T-cell redirecting, bispecific antibody targeting both BCMA (B-cell maturation antigen) and CD3, the T-cell receptor. BCMA is expressed at high levels on multiple myeloma cells.6,7,8,9,10 Teclistamab redirects CD3-positive T-cells to BCMA-expressing myeloma cells to induce killing of tumor cells.5

Teclistamab is currently being evaluated in several monotherapy and combination studies. In 2020, the European Commission and the U.S. FDA each granted teclistamab Orphan Drug Designation for the treatment of multiple myeloma. In January 2021 and June 2021, teclistamab received a PRIority MEdicines (PRIME) designation by the European Medicines Agency (EMA) and Breakthrough Therapy Designation (BTD) by the U.S. FDA, respectively. PRIME offers enhanced interaction and early dialogue to optimize drug development plans and speed up evaluation of cutting-edge, scientific advances that target a high unmet medical need.11 The U.S. FDA grants BTD to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition and is based on preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.12

On December 28, 2021 CStone Pharmaceuticals ("CStone", HKEX: 2616), a leading biopharmaceutical company focused on research, development, and commercialization of innovative immuno-oncology therapies and precision medicines, reported that the new drug application (NDA) of first-in-class precision therapy AYVAKIT (avapritinib) has been approved in Hong Kong, China for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA D842V mutation (Press release, CStone Pharmaceauticals, DEC 28, 2021, View Source [SID1234597807]). The drug is the first precision therapy approved in Hong Kong, China for the treatment of patients with PDGFRA D842V mutant GIST.

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Discovered by CStone’s partner Blueprint Medicines, AYVAKIT is a potent, selective and orally available inhibitor of KIT and PDGFRA mutant kinases. CStone has an exclusive collaboration and license agreement with Blueprint Medicines for the development and commercialization of AYVAKIT and certain other drug candidates in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for AYVAKIT in the rest of the world.

Dr. Frank Jiang, Chairman and CEO of CStone, said, "AYVAKIT is CStone’s first product approval in Hong Kong, China. Earlier this year, AYVAKIT was also approved in Mainland China and Taiwan. We are very glad to provide this innovative treatment to more GIST patients whose tumors harbor the PDGFRA D842V mutation. CStone is committed to bringing forward effective, innovative therapies to patients around the world. In the future, we will strive to accelerate the development of novel therapies to fulfill the unmet medical needs of more cancer patients."

The Hong Kong Department of Health (DOH) has approved AYVAKIT based on data from the NAVIGATOR study, an open-label, dose-escalation/dose-expansion phase I study designed to evaluate the safety and efficacy of AYVAKIT in patients with unresectable or metastatic GIST. In December 2020, the European Journal of Cancer (EJC) published updated data from the NAVIGATOR study enrolling PDGFRA D842V mutant GIST patients. In 38 patients with PDGFRA D842V mutant GIST who received a starting dose of 300 mg or 400 mg once daily, the overall response rate (ORR) was 95% (36/38 patients). In 28 of these patients who had a starting dose of 300 mg once daily, the ORR was 96% (27/28 patients). The disease control rate (DCR) of all dose groups was 100%. The median duration of response (DOR) of all dose groups was 27.6 months. The most common treatment-emergent adverse events were anemia, increased blood bilirubin, decreased white blood cell count, increased blood creatine phosphokinase, increased aspartate aminotransferase, face edema, eyelid edema, decreased neutrophil count and hair color changes. The data showed that AYVAKIT demonstrated robust, durable, and deep clinical activity, with a generally well-tolerated safety profile.

About Gastrointestinal Stromal Tumor (GIST)

GIST is a sarcoma, or tumor of bone or connective tissue, of the GI tract. Tumors arise from cells in the wall of the GI tract and occur most often in the stomach or small intestine. Most patients are diagnosed between the ages of 50 to 80, and diagnosis is typically triggered by GI bleeding, incidental findings during surgery or imaging, and in rare cases, tumor rupture or GI obstruction. About 5 to 6 percent of primary GIST cases are caused by a PDGFRA D842V mutation, the most common PDGFRA exon 18 mutation.

About AYVAKIT (avapritinib)

AYVAKIT (avapritinib) is a kinase inhibitor approved by the Department of Health (DOH), Hong Kong, China and Taiwan Food and Drug Administration (TFDA) under the brand name AYVAKIT for the treatment of adults with unresectable or metastatic GIST harboring a PDGFRA D842V mutation. The National Medical Products Administration (NMPA) of China has approved AYVAKIT for the treatment of adults with unresectable or metastatic GIST harboring the PDGFRA exon 18 mutation, including PDGFRA D842V mutations.

The U.S. Food and Drug Administration (FDA) has approved AYVAKIT for the treatment of two indications: adults with advanced systemic mastocytosis (Advanced SM), including aggressive SM (ASM), SM with an associated hematological neoplasm (SM-AHN) and mast cell leukemia (MCL), and adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. This medicine is approved by the European Commission under the brand name AYVAKYT for the treatment of adults with unresectable or metastatic GIST harboring the PDGFRA D842V mutation. AYVAKIT/AYVAKYT is not approved for the treatment of any other indication in the U.S., Europe or Greater China, or for any indication in any other jurisdiction by any other health authority.

Blueprint Medicines is developing AYVAKIT globally for the treatment of advanced and non-advanced SM. The FDA granted breakthrough therapy designation to AYVAKIT for the treatment of advanced SM, including the subtypes of ASM, SM-AHN, and MCL, and for the treatment of moderate to severe indolent SM.

On December 28, 2021 PharmaCyte Biotech, Inc. (NASDAQ: PMCB), a biotechnology company focused on developing cellular therapies for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that it has successfully completed a 36-month stability study of the cells from its Master Cell Bank (MCB) (Press release, PharmaCyte Biotech, DEC 28, 2021, View Source [SID1234597810]). These cells will be encapsulated and then used to treat locally advanced, inoperable pancreatic cancer (LAPC). This stability study is one of the items that the U.S. Food and Drug Administration (FDA) requires PharmaCyte to complete for its clinical trial product, CypCaps, in an effort to lift the FDA’s clinical hold. This means that the cells used to produce the CypCaps have a shelf life of at least 36 months when stored in a vapor phase of liquid nitrogen. Vapor phase temperature for liquid nitrogen is between -140°C and -180°C.

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PharmaCyte’s Chief Executive Officer, Kenneth L. Waggoner, said of the completed 36-month stability study, "The ongoing study to determine the maximum shelf life of the MCB cells has reached another important milestone. Cells from our MCB successfully completed the required tests to prove that the cells are stable and remain active after being stored frozen for 36 months in a vapor phase of liquid nitrogen.

"Analysis of the cells from our MCB after 36 months showed that the cells passed all of the specified tests, including cell viability, identity testing, sterility, enzyme activity and cell potency as well as pH, label check and appearance of the cells.

"This study will continue in order to determine the maximum shelf life of the cells from our MCB. It is distinct from the other ongoing stability study on the shelf life of our CypCaps that continue to be stored at approximately -80°C. While the storage temperatures are different for the MCB cells and the CypCap cells, the tests for both stability studies are the same."

This ongoing stability study was initiated prior to the submission of PharmaCyte’s Investigational New Drug Application (IND) to the FDA. The information and data obtained from this stability study and other studies will form part of PharmaCyte’s Complete IND Submission of information that PharmaCyte will provide to the FDA to have the clinical hold lifted.

To learn more about PharmaCyte’s pancreatic cancer treatment and how it works inside the body to treat locally advanced inoperable pancreatic cancer, we encourage you to watch the Company’s documentary video complete with medical animations at: View Source

On December 28, 2021 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that the European Medicines Agency (EMA) has validated the Type II Variation application for trastuzumab deruxtecan for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received one or more prior anti-HER2-based regimens (Press release, Daiichi Sankyo, DEC 28, 2021, View Source [SID1234597811]).

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Trastuzumab deruxtecan is a HER2 directed antibody drug conjugate (ADC) being jointly developed by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

Validation confirms that the application is complete and commences the scientific review process by the EMA’s Committee for Medicinal Products for Human Use (CHMP). This application is based on data from the DESTINY-Breast03 phase 3 trial presented at the 2021 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress.

Breast cancer is the most common cancer worldwide, with more than two million cases diagnosed in 2020, resulting in nearly 685,000 deaths globally.1 In Europe, approximately 531,000 cases of breast cancer are diagnosed annually.2 Approximately one in five cases of breast cancer are considered HER2 positive.3 Despite initial treatment with trastuzumab and a taxane, patients with HER2 positive metastatic breast cancer will often experience disease progression.4 More treatment options are needed to further delay progression and extend survival.4,5,6

"We are excited to have submitted a second application this year seeking approval for trastuzumab deruxtecan for a potential third indication in Europe," said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. "With this specific application, we look forward to working closely with the EMA to support the review of trastuzumab deruxtecan to be used in an earlier setting for patients with HER2 positive metastatic breast cancer."

In DESTINY-Breast03, trastuzumab deruxtecan demonstrated a 72% reduction in the risk of disease progression or death compared to trastuzumab emtansine (T-DM1) (hazard ratio [HR] = 0.28; 95% confidence interval [CI]: 0.22-0.37; p=7.8×10-22) in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. The median progression-free survival (PFS) for patients treated with trastuzumab deruxtecan was not reached (95% CI: 18.5-NE) compared to 6.8 months for T-DM1 (95% CI: 5.6-8.2) as assessed by blinded independent central review (BICR). In the secondary endpoint analysis of PFS assessed by investigators, patients treated with trastuzumab deruxtecan experienced an improvement in PFS of 25.1 months (95% CI: 22.1-NE) compared to 7.2 months (95% CI: 6.8-8.3) for T-DM1 (HR=0.26; 95% CI: 0.20-0.35). There was a strong trend towards improved overall survival (OS) with trastuzumab deruxtecan (HR=0.56; 95% CI: 0.36-0.86; p=0.007172), however this analysis is not yet mature and is not statistically significant. Nearly all patients treated with trastuzumab deruxtecan were alive at one year (94.1%; 95% CI: 90.3-96.4) compared to 85.9% of patients treated with T-DM1 (95% CI: 80.9-89.7). Confirmed objective response rate (ORR) was more than doubled in the trastuzumab deruxtecan arm versus the T-DM1 arm (79.7% [n=208; 95% CI: 74.3-84.4] versus 34.2% [n=90; 95% CI: 28.5-40.3]).

The safety profile of the most common adverse events with trastuzumab deruxtecan in DESTINY-Breast03 was consistent with previous clinical trials with no new safety concerns identified. The most common grade 3 or higher drug-related treatment emergent adverse events in the trastuzumab deruxtecan arm were neutropenia (19.1%), thrombocytopenia (7.0%), leukopenia (6.6%), nausea (6.6%), anemia (5.8%), fatigue (5.1%), vomiting (1.6%), increase in ALT (1.6%), decreased appetite (1.2%), increase in AST (0.8%), diarrhea (0.4%) and alopecia (0.4%). Overall, 10.5% of patients had interstitial lung disease (ILD) or pneumonitis related to treatment as determined by an independent adjudication committee. The majority of ILD events (9.7%) were low grade (grade 1 (2.7%) or grade 2 (7.0%)) with two grade 3 (0.8%) events reported. No grade 4 or grade 5 ILD or pneumonitis events occurred.

About HER2 Positive Breast Cancer

Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide.1 More than two million cases of breast cancer were diagnosed in 2020, resulting in nearly 685,000 deaths globally.1 In Europe, approximately 531,000 cases of breast cancer are diagnosed annually.2

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancers.7 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.8 Approximately one in five cases of breast cancer are considered HER2 positive.3

Despite initial treatment with trastuzumab and a taxane, patients with HER2 positive metastatic breast cancer will often experience disease progression.4 More treatment options are needed to further delay progression and extend survival.4,5,6

About DESTINY-Breast03

DESTINY-Breast03 is a global, head-to-head, randomized, open-label, pivotal phase 3 trial evaluating the efficacy and safety of trastuzumab deruxtecan (5.4 mg/kg) versus T-DM1 in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. The primary efficacy endpoint of DESTINY-Breast03 is PFS based on BICR. Secondary efficacy endpoints include OS, ORR, duration of response, PFS based on investigator assessment and safety. DESTINY-Breast03 enrolled 524 patients at multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

About Trastuzumab Deruxtecan

Trastuzumab deruxtecan (fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, trastuzumab deruxtecan is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. Trastuzumab deruxtecan consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Trastuzumab deruxtecan (5.4 mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.

A supplemental New Drug Application is under review in Japan for the treatment of adult patients with HER2 positive unresectable or recurrent breast cancer previously treated with trastuzumab and a taxane, based on the results from the DESTINY-Breast03 trial.

Trastuzumab deruxtecan (6.4 mg/kg) is also approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

A Type II Variation is currently under review by the EMA for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or GEJ adenocarcinoma who have received a prior anti-HER2-based regimen.

About the Trastuzumab Deruxtecan Clinical Development Program

A comprehensive global development program is underway evaluating the efficacy and safety of trastuzumab deruxtecan monotherapy across multiple HER2 targetable cancers including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Trastuzumab deruxtecan was highlighted in the Clinical Cancer Advances 2021 report as one of two significant advancements in the "ASCO Clinical Advance of the Year: Molecular Profiling Driving Progress in GI Cancers," based on data from both the DESTINY-Gastric01 and DESTINY-CRC01 trials, as well as one of the targeted therapy advances of the year in NSCLC based on the interim results of the HER2 mutant cohort of the DESTINY-Lung01 trial.

Trastuzumab deruxtecan recently received its fourth Breakthrough Therapy Designation in the U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received one or more prior anti-HER2-based regimens.

About the Daiichi Sankyo and AstraZeneca Collaboration

Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize trastuzumab deruxtecan in March 2019 and datopotamab deruxtecan (Dato-DXd) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of trastuzumab deruxtecan and datopotamab deruxtecan.

About Daiichi Sankyo in Oncology

The oncology portfolio of Daiichi Sankyo is powered by our team of world-class scientists that push beyond traditional thinking to create transformative medicines for people with cancer. Anchored by our DXd antibody drug conjugate (ADC) technology, our research engines include biologics, medicinal chemistry, modality and other research laboratories in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in the U.S. We also work alongside leading academic and business collaborators to further advance the understanding of cancer as Daiichi Sankyo builds towards our ambitious goal of becoming a global leader in oncology by 2025.

On December 28, 2021 Castle Biosciences, Inc. (Nasdaq: CSTL), a company applying innovative diagnostics to transform disease management and improve patient outcomes, reported that Derek Maetzold, president and chief executive officer, and Frank Stokes, chief financial officer, are scheduled to present a company overview at the 24th Annual Needham Growth Conference on Monday, Jan. 10, 2022, at 12:30 p.m. Eastern time (Press release, Castle Biosciences, DEC 28, 2021, View Source [SID1234597812]).

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A live audio webcast of the company’s presentation will be available by visiting Castle Biosciences’ website at View Source A replay of the webcast will be available for two weeks following the conclusion of the live broadcast.