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Shionogi & Co Ltd announced on 13 Feb 2024 the first peer-reviewed publication of the Phase 3 portion of its pivotal, double-blind, randomized, placebo-controlled Phase 2/3 study (SCORPIO-SR) in patients with mild to moderate COVID-19 in Japan, South Korea and Vietnam in JAMA Network Open. The trial met its primary and key secondary endpoints, making ensitrelvir (generic name: ensitrelvir fumaric acid, Code No: S-217622, hereafter 'ensitrelvir') the first antiviral agent to show both clinical symptom improvement and antiviral effect in a predominantly vaccinated population with Omicron infection regardless of risk factors. The publication reports that treatment with once-daily ensitrelvir in the primary analysis population led to a statistically significant reduction in the time to resolution of five typical COVID-19 symptoms characteristic of Omicron (runny/stuffy nose, sore throat, cough, feeling hot or feverish, and low energy/tiredness1) versus placebo (p=0.04). The median time to symptom resolution was approximately one day shorter in the 125 mg ensitrelvir group versus placebo (approximately 7 days versus 8 days, respectively). Patients included in the primary analysis population were randomized less than 72 hours from symptom onset. More than 90% of patients had received two or more doses of the SARS-CoV-2 vaccine and patients were included regardless of risk factors for severe disease. Original source: Shionogi Inc, website: http://www.shionogi.com/, Copyright Shionogi Inc 2024., research and development; antiviral agents; ensitrelvir fumaric acid; respiratory disease treatments; Shionogi & [...]

Johnson & Johnson announced on 11 Dec 2023 new patient-reported outcomes (PRO) from the Phase 3 CARTITUDE-4 study of Carvykti (ciltacabtagene autoleucel; cilta-cel) demonstrated clinically meaningful improvements in health-related quality of life and meaningful reductions in disease-specific symptoms according to multiple PRO measures in the treatment of adult patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy (LOT). These data were featured as an oral presentation at the 2023 American Society of Hematology (ASH) Annual Meeting (Abstract 1063). In this analysis of the Phase 3 CARTITUDE-4 study, patients in the Carvykti arm reported improved functioning and symptom reduction from baseline, while PRO scores in the standard of care (SOC) regimens, pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) arm trended toward worsening or lower degrees of improvement from baseline for most domains and symptoms. Carvykti exceeded clinically meaningful thresholds for average improvement in global health status (10.1 points), pain (-10.2 points) and the visual analogue scale (8.0 points) from baseline to month 12; improvements in fatigue (-9.1 points) and emotional functioning (9.5 points) neared clinically meaningful thresholds. Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30; 100-point scale), a 30-item instrument designed to measure quality of life in all cancer patients, the analysis showed that results numerically favoured Carvykti for all other domains. The median time until multiple myeloma symptom worsening in the Carvykti arm was 23.7 months compared to 18.9 months in the SOC arm, measured with the Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q; 5-point scale). The CARTITUDE-4 study enrolled 419 patients with lenalidomide-refractory multiple myeloma and one to three prior LOT. At clinical cut-off, 99 patients in the Carvykti arm and 66 in the SOC arm had both baseline and 12-month PRO assessments, representing data prior to progression. PRO compliance was 100% at baseline and decreased with subsequent visits to 74% in the Carvykti and 81% in the SOC arm at month 12.1 Patients were administered EORTC QLQ-C30, EuroQoL 5-Dimension 5-Level (EQ-5D-5L; 100-point scale) and MySIm-Q questionnaires throughout the course of the study. In the primary analysis of CARTITUDE-4 presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Carvykti reduced the risk of disease progression or death by 74% compared to two SOC regimens, PVd or DPd, in adults with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior LOT. Longer-term efficacy and safety data from CARTITUDE-2 cohorts A and B were also presented in an oral presentation at ASH (Abstract 1021). At a median follow-up of approximately 29 months, patients treated with Carvykti in earlier LOT, both those with lenalidomide-refractory multiple myeloma after one to three LOT (cohort A) and those with early relapse (cohort B), experienced deep and durable responses. In the 20 patients in cohort A and 19 in cohort B, treatment with Carvykti resulted in overall response rates of 95% and 100%, respectively. Original source: Johnson & Johnson, website: http://www.jnj.com/, Copyright Johnson & Johnson Services Inc 2023., research and development; anticancer drugs; bortezomib; Carvykti; ciltacabtagene autoleucel; daratumumab; dexamethasone; pomalidomide; Johnson & [...]

On 8 Dec 2023, Pfizer Inc announced the European Commission (EC) has granted conditional marketing authorization for ELREXFIO (elranatamab). ELREFXIO is a targeted immunotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy. ELREXFIO is an off-the-shelf (ready-to-use) B-cell maturation antigen (BCMA)-CD3-directed bispecific antibody (BsAb) immunotherapy that induces deep and durable responses, with a manageable tolerability profile as well as convenient subcutaneous dosing. The conditional marketing authorization for ELREXFIO is valid in all 27 EU member states as well as Iceland, Liechtenstein, and Norway. This authorization follows the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) recommendation for a conditional marketing authorization on 12 Oct 2023. Authorization was based on data from cohort A of the Phase 2 MagnetisMM-3 study (NCT04649359) showing meaningful responses among heavily pretreated RRMM patients - at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody - who received ELREXFIO as their first BCMA-directed therapy. In an analysis of these patients (n=123), the objective response rate was 61%, with a 71% probability of maintaining a response at 15 months. The results from MagnetisMM-3 also established once-every-other-week dosing with ELREXFIO for all responding patients after 24 weeks of weekly therapy, which means less time at the clinic and potentially greater long-term treatment tolerability. Among responding patients who switched to every-other-week dosing at least six months prior to the data cut-off date (n=50), 80% maintained or improved their response after the switch, with 38% attaining a complete response (CR) or better after the switch. These data were published in Nature Medicine. The most common adverse reactions to ELREXFIO are cytokine release syndrome (CRS) (58%), anaemia (54%), neutropenia (45%), fatigue (44%), upper respiratory tract infection (39%), injection site reaction (38%), diarrhoea (38%), pneumonia (37%), thrombocytopenia (36%), lymphopenia (30%), decreased appetite (27%), rash (26%), joint pain (arthralgia) (25%), fever (pyrexia) (27%), hypokalaemia (23%), nausea (21%), and dry skin (21%). Serious adverse reactions are pneumonia (31%), sepsis (15%), CRS (13%), anaemia (6%), upper respiratory tract infection (5%), urinary tract infection (3%), febrile neutropenia (3%), dyspnoea (2%), and pyrexia (2%). Most cases of CRS were Grade 1 (44% of patients), with Grade 2 in 14% and Grade 3 in less than 1% of patients. Due to the risk of CRS and immune effector cell-associated neurotoxicity syndrome (ICANS), patients should be monitored for signs and symptoms for 48 hours after administration of each of the two step-up doses within the ELREXFIO dosing schedule and instructed to remain in proximity of a healthcare facility. In the EU, precautionary hospitalization is not required. Patients are not required to stay near a healthcare facility for the 76-mg first treatment dose. Original source: Pfizer, website: http://www.pfizer.com/, Copyright Pfizer Inc 2023., regulations and rulings; research and development; anticancer drugs; bispecific antibodies; elranatamab; ELREXFIO; therapeutic antibodies; [...]

New data will be presented at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) from the long-term Phase 2b extension trial assessing two-year safety and efficacy of tolebrutinib, Sanofi's investigational, brain-penetrant and bioactive Bruton's tyrosine kinase (BTK) inhibitor, in patients with relapsing forms of MS, including those with highly active disease. Sanofi will also highlight findings from a large-scale proteomic analysis that provides mechanistic validation of tolebrutinib and new insight into protein alterations in MS patients, which may ultimately inform new biomarkers of disease progression to evaluate therapeutic efficacy. Also to be presented at the congress are studies reinforcing the clinical profiles of approved MS therapies AUBAGIO (teriflunomide) and LEMTRADA (alemtuzumab). Original source: Sanofi, website: http://en.sanofi.com/, Copyright Sanofi 2022., research and development; alemtuzumab; enzyme inhibitors; LEMTRADA; monoclonal antibodies; multiple sclerosis drugs; teriflunomide; teriflunomide; therapeutic antibodies; tolebrutinib; [...]

Shionogi & Co Ltd announced that new Fetroja (cefiderocol) data will be presented at IDWeek 2022 including new real-world evidence demonstrating Fetroja's strong efficacy against some of the most difficult-to-treat Gram-negative bacterial infections. New data from PROVE (Retrospective Cefiderocol Chart Review) demonstrated that Fetroja achieved clinical cure in 63% (48/76) of patients with Acinetobacter baumannii infections and 63% (76/120) of patients with Pseudomonas aeruginosa infections. PROVE is an ongoing international retrospective study assessing real-world outcomes and safety of Fetroja in hospitalized patients with Gram-negative bacterial infections. Of the Acinetobacter baumannii infections, 96% were resistant to carbapenems (a last-line antibiotic), and 97% of the Pseudomonas aeruginosa infections were carbapenem-resistant. Safety and tolerability data were generally consistent with the safety profile of Fetroja in clinical studies. Of the total cohort of 220 patients, five had adverse drug reactions (ADR), of which two had rashes, one had an increase in liver function test values, and two had diarrhoea. One patient who was treated with Fetroja experienced a serious ADR (interstitial nephritis). Fetroja was withdrawn in two patients. For both Acinetobacter baumannii and Pseudomonas aeruginosa infections, 79% of patients were alive and 21% of patients died within 30 days of starting Fetroja (30 day all-cause mortality). Additionally, in an analysis of early use experience, including compassionate use where patients had limited treatment options, 80% of patients treated with Fetroja reported clinical cure (74/92) for difficult-to-treat Gram-negative infections (including Pseudomonas aeruginosa and Acinetobacter baumannii). Adverse event (AE) data was reported for 53 patients, of whom 13 (24.5%) reported AEs and 40 (75.5%) did not. Original source: Shionogi Inc, website: http://www.shionogi.com/, Copyright Shionogi Inc 2022., research and development; antibiotics; antiinfectives; carbapenem; cefiderocol; Fetroja; Shionogi & [...]

Bristol Myers Squibb announced on 16 Sep 2022 that the European Commission (EC) has approved the fixed-dose combination of Opdualag (nivolumab and relatlimab) for the first-line treatment of advanced (unresectable or metastatic) melanoma in adults and adolescents 12 years of age and older with tumour cell PD-L1 expression less than 1%. The EC's decision is based upon an exploratory analysis of results from the Phase 2/3 RELATIVITY-047 trial in patients with tumour cell expression less than 1%, which demonstrated that treatment with the fixed-dose combination of the PD-1 inhibitor nivolumab and novel LAG-3-blocking antibody relatlimab more than doubled the median progression-free survival (PFS) compared to nivolumab monotherapy - an established standard of care. No new safety events were identified with the combination when compared to nivolumab monotherapy. The EC decision allows for the use of Opdualag for the first-line treatment of adults and adolescents 12 years of age and older with advanced melanoma and tumour cell PD-L1 expression less than 1% in all European Union member states, as well as Iceland, Liechtenstein, and Norway. The indication in the European Union is based upon an exploratory analysis of the RELATIVITY-047 data in patients with tumour cell PD-L1 expression less than 1%: Efficacy: Median PFS was 6.7 months in patients receiving Opdualag [95% Confidence Interval (CI): 4.7 to 12.0); [Hazard Ratio (HR) 0.68 (0.53, 0.86)] compared to 3.0 months in patients receiving nivolumab monotherapy (95% CI: 2.8 to 4.5). Median overall survival in the Opdualag arm of the trial has not yet been reached [HR 0.78 (0.59, 1.04)]. Safety: The most common adverse reactions were fatigue (41%), musculoskeletal pain (32%), rash (29%), arthralgia (26%), diarrhoea (26%), pruritus (26%), headache (20%), nausea (19%), cough (16%), decreased appetite (16%), hypothyroidism (16%), abdominal pain (14%), vitiligo (13%), pyrexia (12%), constipation (11%), urinary tract infection (11%), dyspnoea (10%), and vomiting (10%). The most common serious adverse reactions were adrenal insufficiency (1.4%), anaemia (1.4%), back pain (1.1%), colitis (1.1%), diarrhoea (1.1%), myocarditis (1.1%), pneumonia (1.1%), and urinary tract infection (1.1%). The incidence of Grade 3-5 adverse reactions was 43% among patients treated with Opdualag compared to 35% among patients receiving nivolumab monotherapy. The RELATIVITY-047 trial also met its primary endpoint of PFS in the all-comer population. Original source: Bristol-Myers Squibb, website: http://www.bms.com/, Copyright Bristol-Myers Squibb 2022., regulations and rulings; research and development; monoclonal antibodies; nivolumab; Opdualag; relatlimab; skin cancer therapeutics; therapeutic antibodies; Bristol Myers [...]