Varubi IV (rolapitant IV) / OPKO Health, TerSera Therap, GSK - LARVOL DELTA

Pharmacokinetics, safety, and efficacy of mixed formulation of fosrolapitant and palonosetron (HR20013) in combination with dexamethasone in patients with solid tumors scheduled for highly emetogenic cisplatin-based chemotherapy: a phase I trial. (PubMed, BMC Med) - P1 | "HR20013 plus dexamethasone had a favorable PK profile, manageable safety, and durable antiemetic efficacy."

Journal • P1 data • PK/PD data • Constipation • Gastroenterology • Gastrointestinal Disorder • Oncology • Solid Tumor

Randomized, Phase III Trial of Mixed Formulation of Fosrolapitant and Palonosetron (HR20013) in Preventing Cisplatin-Based Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: PROFIT. (PubMed, J Clin Oncol) - "HR20013 + DEX was noninferior to FAPR + PALO + DEX for preventing HEC-CINV and well tolerated, with the potential to reduce the impact of CINV on daily life."

CINV • Journal • P3 data • Chemotherapy-Induced Nausea and Vomiting

ROLAPITANT FOR THE PREVENTION OF NAUSEA IN PATIENTS RECEIVING CISPLATIN- OR CARBOPLATIN-BASED CHEMOTHERAPY: ALTERNATIVE METHODS FOR EVALUATING NAUSEA (MASCC-ISOO 2017) - P3; "...To evaluate the effects of rolapitant and RM on efficacy assessments for nausea in the phase 3 trials of rolapitant + 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist (RA) + dexamethasone versus control (placebo + 5-HT3 RA + dexamethasone) for CINV prevention...Rolapitant reduced nausea incidence and RM use in patients receiving cisplatin or carboplatin. RM use did not confound these results."

Clinical • Retrospective data • Biosimilar • Oncology

Efficacy of intravenous (IV) NEPA, a fixed NK1/5-HT3 receptor antagonist (RA) combination, for prevention of CINV following cisplatin- and anthracycline cyclophosphamide (AC)-based chemotherapy (CT) (ESMO 2019) - P3b; "An IV formulation of NEPA (fixed combination of the NK 1 RA, fosnetupitant and 5-HT 3 RA, palonosetron) was recently approved in the US and is under review in Europe...Data was also reviewed from 9 phase III cisplatin and AC studies with other NK 1 RA (aprepitant [APR], fosaprepitant [FOS], rolapitant [ROL]) regimens... Both IV and oral formulations of NEPA along with DEX represent highly effective guideline-compliant single-dose antiemetics. Clinical trial identification: NCT03403712. Legal entity responsible for the study: Helsinn Healthcare."

CINV • Clinical • Oncology • Solid Tumor

Efficacy of an intravenous formulation of NEPA, a fixed combination of fosnetupitant and palonosetron, compared with oral NEPA studies in the prevention of chemotherapy-induced nausea and vomiting (CINV): An analysis of 1026 patient experiences. (ASCO 2018) - P3; "NCT02517021 Background: The approval of oral NEPA, a novel fixed antiemetic combination comprised of the NK1RA netupitant (300 mg) and 5-HT3RA palonosetron (PALO, 0.50 mg), was based on demonstrating superior prevention of CINV over PALO in patients receiving highly emetogenic chemotherapy (HEC) and anthracycline/cyclophosphamide (AC)... Data is compiled from 4 pivotal registration studies in adult chemotherapy-nave patients with solid tumors undergoing predominantly cisplatin-based HEC...All patients received dexamethasone on Days 1-4... Both IV and oral formulations of NEPA represent safe, effective, and convenient single-dose prophylactic antiemetics targeting two distinct CINV pathways, offering comparable options for clinicians and patients in different settings."

CINV • Clinical • Solid Tumor

Safety of intravenous (IV) NEPA and oral NEPA for prevention of CINV in patients (pts) with breast cancer (BC) receiving anthracycline/cyclophosphamide (AC) chemotherapy (CT). (ASCO 2019) - P3b; "Background: NEPA, a combination antiemetic agent [NK1 receptor antagonist (RA) netupitant (oral) or fosnetupitant (IV) + 5-HT3RA palonosetron] offers 5-day CINV prevention with a single-dose...In a Phase 3 study in pts receiving cisplatin-based CT, there were no infusion site or anaphylactic reactions related to IV NEPA. In contrast, hypersensitivity reactions and anaphylaxis have been reported with IV aprepitant, fosaprepitant and rolapitant, with the highest rate (35%) for fosaprepitant in the AC setting... There were no infusion-site AEs related to IV NEPA and no anaphylaxis reported for either formulation. Consistent with the pivotal study, IV NEPA is safe and effective in pts receiving AC. As a simplified single-dose formulation, IV NEPA may be better tolerated than other NK1 RAs."

CINV • Clinical

TESARO provides pipeline update at ASCO investor briefing (Tesaro Press Release) - "TESARO...today provided an update on its clinical development pipeline during an investor briefing and webcast held in conjunction with the American Society for Clinical Oncology...FDA) has accepted for review the New Drug Application (NDA) for an intravenous (IV) formulation of rolapitant...action date under the Prescription Drug User Fee Act (PDUFA) of January 11, 2017...provided an update on its Phase 3 NOVA trial of niraparib in patients with ovarian cancer. A sufficient number of progression free survival (PFS) events has been reached...announced FDA clearance of its Investigational New Drug (IND) application for TSR-022...A Phase 1 study for TSR-022 is planned to begin in mid-2016."

Anticipated new P1 trial • Anticipated P3 data: top line • Conference • IND • PDUFA date • sNDA • Oncology

Tesaro announces fourth-quarter 2015 operating results (Tesaro Press Release) - "TESARO anticipates achieving the following key objectives: [1] Continue to execute on the VARUBI commercial launch in the United States; [2] Submit the NDA for IV rolapitant in Q1 2016; [3] Submit the oral rolapitant Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in Q2 2016...."

Anticipated EU regulatory • Anticipated launch US • Anticipated NDA • Oncology

Rolapitant: First Global Approval. (PubMed) - "Phase II development of rolapitant in postoperative nausea and vomiting, and cough appears to have been discontinued. This article summarizes the milestones in the development of rolapitant leading to the first approval for the prevention of CINV."

Journal • Biosimilar

Rolapitant for the prevention of chemotherapy-induced nausea and vomiting in breast cancer patients receiving multiple cycles of emetogenic chemotherapy (SABCS 2016) - "The regimens were cisplatin-based (n=36), AC-based (n=681) or other (n=166; carboplatin, cyclophosphamide, etc). Rolapitant added to 5-HT3 RA and dexamethasone therapy improved CINV control and was safe and well-tolerated in pts with breast cancer receiving multiple cycles of emetogenic chemotherapy, mostly AC and carboplatin, historically a high-risk population for CINV."

Clinical • Retrospective data • Biosimilar • Breast Cancer • Oncology

Compatibility and Stability of VARUBI (Rolapitant) Injectable Emulsion Admixed with Intravenous Granisetron Hydrochloride. (PubMed, Int J Pharm Compd) - "Prophylaxis or therapy with a combination of a neurokinin 1 (NK-1) receptor antagonist (RA), a 5-hydroxytryptamine- 3 (5-HT3) RA, and dexamethasone is recommended by international antiemesis guidelines for the prevention of chemotherapy-induced nausea and vomiting for patients receiving highly emetogenic chemotherapy and for select patients receiving moderately emetogenic chemotherapy...Granisetron Hydrochloride Injection USP is one of the 5-HT3 RAs indicated for the prevention of nausea and/or vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin...No decrease of drug concentration (or potency) of any admixed components occurred in the samples stored at the two conditions and time periods studied based on high-performance liquid chromatographic analysis. The levels of impurities stayed below the safety limits set by International Conference on Harmonisation during the study period."

Journal • Biosimilar • Oncology

TESARO announces first-quarter 2016 operating results (Tesaro Press Release) - "TESARO...today reported operating results for first quarter 2016 and provided an update on the Company's development programs...Product revenue for the first quarter of 2016 totaled $0.2 million and included sales of VARUBI to specialty pharmacy customers...anticipates achieving the following key objectives: [1] Continue to execute on the VARUBI commercial launch in the United States; [2] Launch IV rolapitant into the U.S. market in 2017, pending FDA approval."

Anticipated launch • Commercial • Sales • Oncology

Tesaro receives complete response letter for rolapitant IV from U.S. FDA (Tesaro Press Release) - "TESARO...today announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding the rolapitant IV New Drug Application (NDA) for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy. FDA requested additional information regarding the in vitro method utilized to demonstrate comparability of drug product produced at the two proposed commercial manufacturers for rolapitant IV that were included in the NDA...expect to enable approval in the first half of 2017."

Anticipated NDA • FDA event • Oncology

Tesaro outlines business priorities and strategic outlook for 2016 (Tesaro Press Release) - "TESARO anticipates achieving the following milestones related to VARUBI in 2016: Continue to execute on the VARUBI commercial launch in the United States; Submit the NDA for intravenous (IV) rolapitant in Q1; and Submit the oral rolapitant Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in Q2."

Anticipated EU regulatory • Anticipated launch US • Anticipated NDA • Oncology

Varubi IV: PDUFA date for CINV October 25, 2017 (Tesaro) - ASCO Investor & Analyst Briefing

PDUFA date • Oncology

Varubi IV: Expiry of US patent related to methods of treating nausea and/or emesis in July 2032 (Tesaro) - Annual Report 2017: Patent protection in multiple foreign jurisdictions related to methods of treating nausea and/or emesis until 2030

Patent • Oncology

Tesaro: Jefferies Healthcare Conference (Tesaro) - “Bioequivalence Demonstrated to Rolapitant Oral”; "Similar Exposure (AUC) for Oral and IV formulations"

P1 data • Oncology

Varubi IV: Newly added patents in Orange Book (Orange Book) - Expiration of patents on December 8, 2023, April 4, 2027, January 18, 2029, December 17, 2022, July 14, 2032

Patent • Oncology

OPKO: Jefferies Global Healthcare Conference 2016 (OPKO health) - PDUFA date for CINV on January 11, 2017

PDUFA date • Oncology

Tesaro announces updates to the U.S. prescribing information for Varubi (rolapitant) injectable emulsion (Tesaro Press Release) - "TESARO...announced that it has updated the VARUBI (rolapitant) injectable emulsion package insert in collaboration with the U.S. Food and Drug Administration (FDA). VARUBI injectable emulsion is a substance P/neurokinin (NK-1) receptor antagonist indicated for the prevention of delayed nausea and vomiting associated with chemotherapy in adults. The changes to the labeling include modifications to the CONTRAINDICATIONS, WARNINGS and PRECAUTIONS, and ADVERSE REACTIONS sections."

FDA event • Oncology

TESARO announces U.S. FDA approval of Varubi IV for delayed nausea and vomiting associated with cancer chemotherapy (Tesaro Press Release) - "TESARO...today announced that the U.S. Food and Drug Administration (FDA) has approved VARUBI® (rolapitant) IV in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy...U.S. commercial launch planned for November."

Launch US • NDA • Oncology

TESARO announces availability of Varubi (rolapitant) IV for delayed nausea and vomiting associated with cancer chemotherapy in the United States (GlobeNewswire) - "TESARO...today announced that VARUBI® (rolapitant) IV, is now available in the United States. The U.S. Food and Drug Administration (FDA) approved VARUBI injectable emulsion on October 25, 2017, for use in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy."

Launch US • Oncology

Pharmacokinetics, Safety, and Tolerability of Rolapitant Administered Intravenously Following Single Ascending and Multiple Ascending Doses in Healthy Subjects. (PubMed, Clin Pharmacol Drug Dev) - "Rolapitant is a selective and long-acting neurokinin-1 receptor antagonist approved in an oral formulation in combination with dexamethasone and a 5-hydroxytryptamine type 3 receptor antagonist for the prevention of delayed chemotherapy-induced nausea and vomiting in adults. The most common rolapitant-related treatment-emergent adverse events were headache, dry mouth, and dizziness, which were predominantly mild in severity. Overall, the pharmacokinetic and safety profiles of IV rolapitant were consistent with those of the oral formulation."

Clinical • Journal • PK/PD data

Symptom management for patients with relapsed and refractory multiple myeloma receiving therapy with selinexor (Xpovio™) (ONS 2020) - "Supportive Care: Common toxicities include nausea, anorexia, fatigue, thrombocytopenia and hyponatremia.1 28 of the123 patients enrolled in STORM were treated at MSH and demonstrated longer overall response rates (53.6% in MSH vs. 26.2% in overall STORM population) and less discontinuations due to toxicities (3.7% vs 18.8%).2 Our methods included starting the following prophylactic medications prior to treatment: ondansetron 8 mg PO three times a day, olanzapine 2.5 mg PO daily at night, and rolapitant 180 mg PO every two weeks...Platelet transfusions and romiplostim 10 mcg/kg SC weekly on selinexor off days were used to mitigate thrombocytopenia... Patient education should include discussion of common toxicities and appointments for evaluation/supportive care measures. Optimization of supportive care and oral adherence is critical to maintain patients on treatment longer to get better response rates in this triple class refractory population."

Clinical

The safety of rolapitant for the treatment of nausea and vomiting associated with chemotherapy. (PubMed, Expert Opin Drug Saf) - "Significant improvements in the control of chemotherapy-induced nausea and vomiting have occurred in the past 15 years with the introduction of new antiemetic agents 5-HT3, receptor antagonists, neurokinin-1 receptor antagonists, and olanzapine. Oral (aprepitant, 2003; netupitant, 2014; rolapitant, 2015) neurokinin-1 receptor antagonists have been developed along with intravenous formulations (fosaprepitant, NEPA, rolapitant, HTX-019) for the prevention of chemotherapy-induced nausea and vomiting.Areas covered: This review presents a description of the safety and efficacy of rolapitant along with a comparison to the other oral and intravenous formulations of the neurokinin-1 receptor antagonists.Expert opinion: Oral rolapitant has been demonstrated in clinical trials to be safe and effective in controlling chemotherapy-induced nausea and vomiting in patients receiving moderately and highly emetogenic chemotherapy. Rolapitant has a longer half-life (180 hours) than other..."

Clinical • Journal