Pirarubicin Hydrochloride

Dec. 1, 2021 13:00 UTC Additional analyses of DESTINY-Breast03 trial of ENHERTU and updated results from triple negative breast cancer cohort of TROPION-PanTumor01 trial of datopotamab deruxtecan to be highlighted Daiichi Sankyo to hold annual R&D Day following SABCS to provide updates across entire R&D portfolio MUNICH & BASKING RIDGE, N.J.--(BUSINESS WIRE)-- Daiichi Sankyo Company, Ltd. (hereafter, Daiichi Sankyo) will present new breast cancer research data across its DXd ADC portfolio at the 2021 San Antonio Breast Cancer Symposium (#SABCS21) to be held December 7 to 10, 2021. Additional analyses from the head-to-head DESTINY-Breast03 phase 3 trial of ENHERTU® (trastuzumab deruxtecan) versus trastuzumab emtansine (T-DM1) in patients with previously treated HER2 positive metastatic breast cancer along with updated results from the triple negative breast cancer (TNBC) cohort of the TROPION-PanTumor01 phase 1 trial of datopotamab deruxtecan (Dato-DXd) will be highlighted in oral presentations. Trials-in-progress from other ongoing breast cancer trials in the DESTINY clinical development program of ENHERTU as well as a collaborative window of opportunity study conducted by SOLTI Breast Cancer Research Group with patritumab deruxtecan (HER3-DXd) in patients with previously untreated early stage breast cancer also will be featured. “Our goal is to continuously improve the standard of care in patients with breast cancer across different subtypes and treatment settings including neoadjuvant, adjuvant and metastatic disease with our innovative ADC portfolio,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “We look forward to presenting updates from the DESTINY-Breast03 trial and TROPION-PanTumor01 trial, two important trials that demonstrate the strength and potential of our DXd ADC technology in creating transformative medicines for patients with cancer.” Following SABCS, Daiichi Sankyo will hold its annual R&D Day for investors and analysts on Tuesday, December 14, 2021 at 5:30 pm EST/Wednesday, December 15, 2021 at 7:30 am JST. Company executives will provide an overview of Daiichi Sankyo’s research data presented at SABCS and the American Society of Hematology (ASH) annual meetings, provide updates on the company’s R&D strategy and address questions from investors and analysts. Following is an overview of breast cancer research data from the DXd ADC portfolio of Daiichi Sankyo to be presented at SABCS 2021: Presentation Title Author Abstract # Presentation Details ENHERTU (T-DXd) Clinical Data Trastuzumab deruxtecan (T-DXd) vs. trastuzumab emtansine (T-DM1) in patients with HER2 positive metastatic breast cancer: results of the randomized phase 3 study: DESTINY-Breast03 S. Hurvitz GS3-01 Oral Presentation; General Session: 3 Thursday, December 9 8:45 AM – 11:30 AM CST Trastuzumab deruxtecan (T-DXd) in previously treated HER2 positive metastatic or unresectable breast cancer: first real-life data from the cohort temporary authorization for use program in France T. Petit P2-13-26 Poster Poster Session 2: Treatment - Therapeutic Strategies: HER2 Targeted Therapy Wednesday, December 8 5:00 PM – 6:30 PM CST Trials-In-Progress Trastuzumab deruxtecan (T-DXd) vs. trastuzumab emtansine (T-DM1) in high-risk patients with HER2 positive, residual invasive early breast cancer after neoadjuvant therapy: a randomized, phase 3 trial: DESTINY-Breast05 C.E. Geyer, Jr. OT1-02-03 Poster Ongoing Trials Poster Session 1: Antibody-Drug Conjugates Wednesday, December 8 5:00 PM – 6:30 PM CST Phase 3 study of trastuzumab deruxtecan (T-DXd) with or without pertuzumab vs. a taxane, trastuzumab and pertuzumab in first-line, human epidermal growth factor receptor 2 positive metastatic breast cancer: DESTINY-Breast09 S.M. Tolaney OT1-14-02 Poster Ongoing Trials Poster Session 1: HER2 Mab Wednesday, December 8 5:00 PM – 6:30 PM CST A phase 3, open-label trial of neoadjuvant trastuzumab deruxtecan (T-DXd) monotherapy or T-DXd followed by THP compared with ddAC-THP in patients with high-risk HER2 positive early-stage breast cancer: DESTINY-Breast11 N. Harbeck OT1-12-04 Poster Ongoing Trials Poster Session 1: HER2 Wednesday, December 8 5:00 PM – 6:30 PM CST Open-label, multinational, multicenter, phase 3b/4 study of trastuzumab deruxtecan (T-DXd) in patients with or without baseline brain metastasis with previously treated advanced/metastatic human epidermal growth factor receptor 2 positive breast cancer: DESTINY-Breast12 N.U. Lin OT2-26-01 Poster Ongoing Trials Poster Session 2: Targeted Therapy - T-DXd, Brain Mets Thursday, December 9 5:00 PM – 6:30 PM CST Randomized study comparing electronic patient reported outcomes monitoring with routine follow-up during trastuzumab deruxtecan (T-DXd) treatment in patients with inoperable or metastatic breast cancer (PRO-DUCE study) T. Sangai OT1-12-08 Poster Ongoing Trials Poster Session 1: HER2 Wednesday, December 8 5:00 PM – 6:30 PM CST Pre-Clinical Data Activity and tolerability of combination of trastuzumab deruxtecan (T-DXd) with the pan-AKT inhibitor capivasertib in preclinical HER2 positive and HER2 low breast cancer models A. Bashi Cheraghchi P2-13-23 Poster Poster Session 2: Treatment - Therapeutic Strategies: HER2 Targeted Therapy Wednesday, December 8 5:00 PM – 6:30 PM CST Presentation Title Author Abstract # Presentation Details Activity and tolerability of combination of trastuzumab deruxtecan (T-DXd) with olaparib in preclinical HER2 positive and HER2 low breast cancer models T. Proia P2-13-18 Poster Poster Session 2: Treatment - Therapeutic Strategies: HER2 Targeted Therapy Wednesday, December 8 5:00 PM – 6:30 PM CST Datopotamab Deruxtecan (Dato-DXd) Datopotamab deruxtecan (Dato-DXd) in advanced/metastatic HER2 negative breast cancer: Results from the phase 1 TROPION-PanTumor01 study I. Krop GS1-05 Oral Presentation; General Session 1 Tuesday, December 7 8:15 AM – 10:45 AM CST Patritumab Deruxtecan (HER3-DXd) – Collaborative Studies Activity of patritumab deruxtecan (HER3-DXd), a HER3 directed antibody drug conjugate, in early breast cancer according to ERBB3 expression: Interim analysis results of a window of opportunity study (SOLTI-1805 TOT-HER3) A. Prat PD13-04 Spotlight Poster Discussion Spotlight Poster Discussion 13: Novel Therapeutics Friday, December 10 7:00 AM – 8:30 AM CST Antitumor activity of patritumab deruxtecan (HER3-DXd), a HER3 directed antibody drug conjugate across a diverse panel of breast cancer patient-derived xenografts A. Òdena P5-13-14 Poster Poster Session 5: Prognostic and Predictive Factors: Predictive Biomarkers for Targeted Therapies Friday, December 10 7:00 AM – 8:30 AM CST About the DXd ADC Portfolio of Daiichi Sankyo The DXd ADC portfolio of Daiichi Sankyo consists of six ADCs with five in clinical development across multiple types of cancer. The company’s three lead ADCs include ENHERTU, a HER2 directed ADC, datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca; and patritumab deruxtecan (HER3-DXd), a HER3 directed ADC. Two additional ADCs, DS-7300 (B7-H3) and DS-6000 (CDH6), are being developed through a strategic collaboration with Sarah Cannon Research Institute. Each ADC is designed using Daiichi Sankyo’s proprietary DXd ADC technology to target and deliver chemotherapy inside cancer cells that express a specific cell surface antigen. Each ADC is composed of a monoclonal antibody attached to a topoisomerase I inhibitor payload (an exatecan derivative, DXd) via a tetrapeptide-based cleavable linker. ENHERTU (5.4 mg/kg) (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in U.S. only) 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. ENHERTU (6.4 mg/kg) is approved in Israel, Japan, Singapore and U.S. 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 European Medicines Agency (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. ENHERTU is approved in the U.S. with Boxed WARNINGS for Interstitial Lung Disease and Embryo-Fetal Toxicity. For more information, please see the accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide. Datopotamab deruxtecan, patritumab deruxtecan, DS-7300 and DS-6000 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. U.S. Important Safety Information for ENHERTU Indications ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated 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 in the metastatic setting. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen. WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms. Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception. Contraindications None. Warnings and Precautions Interstitial Lung Disease / Pneumonitis Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks. Metastatic Breast Cancer In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, ILD occurred in 9% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 2.6% of patients treated with ENHERTU. Median time to first onset was 4.1 months (range: 1.2 to 8.3). Locally Advanced or Metastatic Gastric Cancer In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21.0). Neutropenia Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L) interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L) interrupt ENHERTU until resolved to Grade 2 or less. Reduce dose by one level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3ºC or a sustained temperature of ≥38ºC for more than 1 hour), interrupt ENHERTU until resolved. Reduce dose by one level. Metastatic Breast Cancer In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU 5.4mg/kg, a decrease in neutrophil count was reported in 62% of patients. Sixteen percent had Grade 3 or 4 decrease in neutrophil count. Median time to first onset of decreased neutrophil count was 23 days (range: 6 to 547). Febrile neutropenia was reported in 1.7% of patients. Locally Advanced or Metastatic Gastric Cancer In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients. Left Ventricular Dysfunction Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. In the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU, two cases (0.9%) of asymptomatic LVEF decrease were reported. In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment. Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. Embryo-Fetal Toxicity ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months after the last dose of ENHERTU. Additional Dose Modifications Thrombocytopenia For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less. Reduce dose by one level. Adverse Reactions Metastatic Breast Cancer The safety of ENHERTU was evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg in DESTINY-Breast01 and Study DS8201-A-J101. ENHERTU was administered by intravenous infusion once every three weeks. The median duration of treatment was 7 months (range: 0.7 to 31). Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were interstitial lung disease, pneumonia, vomiting, nausea, cellulitis, hypokalemia, and intestinal obstruction. Fatalities due to adverse reactions occurred in 4.3% of patients including interstitial lung disease (2.6%), and the following events occurred in one patient each (0.4%): acute hepatic failure/acute kidney injury, general physical health deterioration, pneumonia, and hemorrhagic shock. ENHERTU was permanently discontinued in 9% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 33% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, thrombocytopenia, leukopenia, upper respiratory tract infection, fatigue, nausea, and ILD. Dose reductions occurred in 18% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, and neutropenia. The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (79%), white blood cell count decreased (70%), hemoglobin decreased (70%), neutrophil count decreased (62%), fatigue (59%), vomiting (47%), alopecia (46%), aspartate aminotransferase increased (41%), alanine aminotransferase increased (38%), platelet count decreased (37%), constipation (35%), decreased appetite (32%), anemia (31%), diarrhea (29%), hypokalemia (26%), and cough (20%). Locally Advanced or Metastatic Gastric Cancer The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma in DESTINY‑Gastric01. Patients intravenously received at least one dose of either ENHERTU (N=125) 6.4 mg/kg once every three weeks or either irinotecan (N=55) 150 mg/m2 biweekly or paclitaxel (N=7) 80 mg/m2 weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) in the ENHERTU group and 2.8 months (range: 0.5 to 13.1) in the irinotecan/paclitaxel group. Serious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients who received ENHERTU were decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in one patient each (0.8%). ENHERTU was permanently discontinued in 15% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 62% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and hypokalemia. Dose reductions occurred in 32% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia. The most common (≥20%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (75%), white blood cell count decreased (74%), neutrophil count decreased (72%), lymphocyte count decreased (70%), platelet count decreased (68%), nausea (63%), decreased appetite (60%), anemia (58%), aspartate aminotransferase increased (58%), fatigue (55%), blood alkaline phosphatase increased (54%), alanine aminotransferase increased (47%), diarrhea (32%), hypokalemia (30%), vomiting (26%), constipation (24%), blood bilirubin increased (24%), pyrexia (24%), and alopecia (22%). Use in Specific Populations Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months following the last dose of ENHERTU. Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose. Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 7 months following the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months following the last dose. Infertility: ENHERTU may impair male reproductive function and fertility. Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients. Geriatric Use: Of the 234 patients with HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, 26% were ≥65 years and 5% were ≥75 years. No overall differences in efficacy were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (53%) as compared to younger patients (42%). Of the 125 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were ≥65 years and 14% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor. To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch. Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide. 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, 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. About Daiichi Sankyo Daiichi Sankyo is dedicated to creating new modalities and innovative medicines by leveraging our world-class science and technology for our purpose “to contribute to the enrichment of quality of life around the world.” In addition to our current portfolio of medicines for cancer and cardiovascular disease, Daiichi Sankyo is primarily focused on developing novel therapies for people with cancer as well as other diseases with high unmet medical needs. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 16,000 employees around the world draw upon a rich legacy of innovation to realize our 2030 Vision to become an “Innovative Global Healthcare Company Contributing to the Sustainable Development of Society.” For more information, please visit .

Crofelemer is a novel, oral plant-based non-opioid antidiarrheal medication SAN FRANCISCO, CA / ACCESSWIRE / November 19, 2021 / Jaguar Health, Inc. (NASDAQ:JAGX) today announced topline results of the third-party, investigator-initiated Phase 2 HALT-D trial evaluating crofelemer for the prevention of chemotherapy-induced diarrhea (CID) in HER2-positive breast cancer patients being treated with trastuzumab, pertuzumab and a taxane.1 These therapies are known to cause CID in up to 80% of breast cancer patients, reaching grade 3 (requiring hospitalization) in 8-12% of patients.2-5 CID can have a negative impact on quality of life, particularly when it persists through much of the course of chemotherapy, and may result in stopping cancer treatment. There are no medications currently approved for CID. Jaguar Health believes crofelemer is the only antidiarrheal medication under clinical investigation that specifically targets the underlying mechanism of CID. As reported in the abstract (Publication Number: P5-18-09) posted by the San Antonio Breast Cancer Symposium (SABCS), the study included 51 breast cancer patients randomly assigned to either crofelemer or control standard of care with no prophylactic antidiarrheal medications. Findings showed that the primary endpoint - the incidence of having diarrhea for two or more days - was not statistically different for the two groups since about 70% of patients had this outcome regardless of cycle or CID treatment group, which is consistent with the experience of CID in patients receiving these chemotherapy regimens. The crofelemer group demonstrated better outcomes compared to the control group for a number of key secondary endpoints:1 Lower incidence of grade 2 or higher-grade diarrhea for the crofelemer group compared to the control group during cycle 2, based on patient-reported outcomes: 9.0% vs. 33.3%. Lower incidence of grade 2 or higher-grade diarrhea for the crofelemer group compared to the control group during cycle 2, based on investigator assessments: 9.5% vs. 41.1%. No patients in the crofelemer group experienced grade 3 or grade 4 diarrhea during cycle 2 compared to 17.6% of patients in the control group, based on patient-reported outcomes. "A number of findings of secondary endpoints were significantly in favor of crofelemer," said lead study investigator Paula Pohlmann, MD, PhD, formerly from Georgetown University and now Associate Professor, MD Anderson Cancer Center. "These positive HALT-D data not only support further testing of crofelemer in CID, they also provide evidence for the selection of more appropriate endpoints to assess improvements in CID, which take into account both the frequency and severity of diarrhea." "These are important findings for patients with CID and the physicians who treat them," said Sandra M. Swain, MD, Associate Dean for Research Development at the Georgetown University Medical Center and the senior investigator of the study. "The data from this HALT-D trial gives us hope that the side effect of diarrhea seen with very effective chemotherapy for HER2-positive breast cancer can be diminished and make the treatment more tolerable for patients." Jaguar Health President and CEO Lisa Conte said, "We are pleased by the findings of the HALT-D study. A major challenge in studying CID is the lack of consensus on how to measure it. Not only did the HALT-D study show the potential benefit of crofelemer for this indication, we believe it supports the endpoints we selected for our ongoing pivotal Phase 3 OnTarget trial. We want to thank the investigators for their important work on this study and we look forward to continuing to advance the development of crofelemer to potentially address the serious consequences of CID on both a cancer patient's dignity and their ability to continue their cancer treatment." The HALT-D study is separate from the OnTarget study, the pivotal Phase 3 clinical trial of crofelemer for prophylaxis of diarrhea in adult cancer patients receiving targeted therapy. OnTarget was initiated in October 2020 by Napo Pharmaceuticals, Jaguar Health's wholly owned subsidiary. More About HALT-D1 The patients in the HALT-D trial were scheduled for at least three consecutive 21-day cycles of chemotherapy with THP (trastuzumab and pertuzumab with paclitaxel or docetaxel) or TCHP (docetaxel, carboplatin, trastuzumab and pertuzumab). Patients were randomized 1:1 to receive crofelemer during chemotherapy cycles 1 and 2, or standard-of-care with no prophylactic antidiarrheal therapy. All patients received breakthrough antidiarrheal medications as needed. The primary endpoint was the incidence of any diarrhea (grades 1-4) for two or more consecutive days. Secondary endpoints included the incidence of any diarrhea and of severe diarrhea (grades 3 or 4), time to onset and duration of diarrhea, stool consistency, frequency of breakthrough antidiarrheal medication use, and quality-of-life measures. Data included physician assessments and patient-reported outcomes. Full results for the secondary endpoints will be presented in the virtual and narrated poster available on the SABCS website and presented in person at the SABCS poster session from 7:00 am to 8:30 am CT on December 10. The full study results are expected to be submitted for publication in a medical journal. Jaguar Health plans to sponsor a closed satellite in-person/virtual event at SABCS on CID in breast cancer patients. The date and timing for the event will be provided in an upcoming announcement. The HALT-D study was sponsored and conducted by Georgetown Lombardi Comprehensive Cancer Center and MedStar Health, and funded by Genentech, a member of the Roche Group. The crofelemer used in the study was provided by Jaguar Health. About Chemotherapy-Induced Diarrhea A significant proportion of patients undergoing cancer therapy experience diarrhea, and diarrhea has the potential to cause dehydration, potential infections, and non-adherence to treatment in this population. Novel "targeted cancer therapy" agents, such as epidermal growth factor receptor (EGFR) antibodies and tyrosine kinase inhibitors (TKIs), with or without cycle chemotherapy agents, may cause increased electrolyte and fluid content in the gut lumen, which results in passage of loose/watery stools (i.e., diarrhea). Diarrhea has been reported as one of the most common side effects of TKIs and may result in cancer therapy drug holidays or reductions from therapeutic dose, potentially impacting patient outcome. Diarrhea is also a common side effect of some approved CDK 4/6 inhibitors. About Crofelemer Crofelemer is a novel, oral plant-based medicine purified from the red bark sap, also referred to as "dragon's blood," of the medicinal Croton lechleri tree in the Amazon Rainforest. Napo has established a sustainable harvesting program, under fair trade practices, for crofelemer to ensure a high degree of quality, ecological integrity, and support for Indigenous communities. Crofelemer is the active ingredient in Mytesi®, Jaguar Health's FDA-approved drug to treat noninfectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy (ART). It is the only oral plant-based prescription medicine approved under FDA Botanical Guidance. About Jaguar Health, Inc., Napo Pharmaceuticals, Inc. & Napo EU S.p.A. Jaguar Health, Inc. is a commercial stage pharmaceuticals company focused on developing novel, plant-based, non-opioid, and sustainably derived prescription medicines for people and animals with GI distress, specifically chronic, debilitating diarrhea. Our wholly owned subsidiary, Napo Pharmaceuticals, Inc., focuses on developing and commercializing proprietary plant-based human gastrointestinal pharmaceuticals from plants harvested responsibly from rainforest areas. Our Mytesi® (crofelemer) product is approved by the U.S. FDA for the symptomatic relief of noninfectious diarrhea in adults with HIV/AIDS on antiretroviral therapy and the only oral plant-based prescription medicine approved under FDA Botanical Guidance. Napo Pharmaceuticals' wholly owned Italian subsidiary, Napo EU S.p.A., focuses on expanding crofelemer access in Europe. For more information about Jaguar Health, please visit For more information about Napo Pharmaceuticals, visit For more information about Napo EU, visit About Mytesi® Mytesi® (crofelemer delayed release tablets) is an antidiarrheal indicated for the symptomatic relief of noninfectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy (ART). Mytesi® is not indicated for the treatment of infectious diarrhea. Infectious etiologies of diarrhea should be ruled out by a physician before starting Mytesi®. If infectious etiologies are not considered, there is a risk that patients with infectious etiologies will not receive the appropriate therapy and their disease may worsen. In clinical studies, the most common adverse reactions occurring at a rate greater than placebo were upper respiratory tract infection (5.7%), bronchitis (3.9%), cough (3.5%), flatulence (3.1%), and increased bilirubin (3.1%). More information and complete Prescribing Information are available at Mytesi.com. Forward-Looking Statements Certain statements in this press release constitute "forward-looking statements." These include statements regarding Jaguar Health's belief that crofelemer is the only antidiarrheal medication under clinical investigation that specifically targets the underlying mechanism of CID, Jaguar Health's belief that the HALT-D study supports the endpoints Jaguar Health selected for its ongoing pivotal Phase 3 OnTarget trial, the expectation that the study results will be submitted for publication in a medical journal, and Jaguar Health's expectation that it will sponsor a closed satellite in-person/virtual event at SABCS on CID in breast cancer patients. In some cases, you can identify forward-looking statements by terms such as "may," "will," "should," "expect," "plan," "aim," "anticipate," "could," "intend," "target," "project," "contemplate," "believe," "estimate," "predict," "potential" or "continue" or the negative of these terms or other similar expressions. The forward-looking statements in this release are only predictions. Jaguar Health has based these forward-looking statements largely on its current expectations and projections about future events. These forward-looking statements speak only as of the date of this release and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond Jaguar Health's control. Except as required by applicable law, Jaguar Health does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. CONTACT: Peter Hodge Jaguar Health, Inc. phodge@jaguar.health Jaguar-JAGX References Pohlmann PR, Graham D, Wu T, et al. HALT-D: A randomized open label phase 2 study of crofelemer for the prevention of chemotherapy induced diarrhea (cid) in patients with breast cancer receiving trastuzumab, pertuzumab, and a taxane. Abstract 2142 of poster presentation P5-18-09. Available sabcs.org (San Antonio Breast Cancer Symposium). Accessed November 19, 2021. Baselga J, Cortés J, Kim SB, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366(2):109-119. doi:10.1056/NEJMoa1113216 Dang C, Iyengar N, Datko F, et al. Phase II study of paclitaxel given once per week along with trastuzumab and pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer [published correction appears in J Clin Oncol. 2019 Feb 1;37(4):354]. J Clin Oncol. 2015;33(5):442-447. doi:10.1200/JCO.2014.57.1745 Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25-32. doi:10.1016/S1470-2045(11)70336-9 Schneeweiss A, Chia S, Hickish T, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24(9):2278-2284. doi:10.1093/annonc/mdt182 SOURCE: Jaguar Health, Inc. View source version on accesswire.com: