TAGRISSO Plus Chemotherapy Granted Priority Review in the US for Patients with EGFR-Mutated Advanced Lung Cancer

 AstraZeneca's supplemental New Drug Application (sNDA) for TAGRISSO (osimertinib) combined with chemotherapy has been accepted and granted Priority Review by the US Food and Drug Administration (FDA).

This application aims to treat adult patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC). The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that have the potential to offer significant improvements over existing options. 

This can be demonstrated through safety or efficacy enhancements, prevention of serious conditions, or improved patient compliance. The anticipated FDA action date for their regulatory decision, known as the Prescription Drug User Fee Act date, is expected during the first quarter of 2024. 

 Each year, approximately 2.2 million people diagnosed with lung cancer globally Out of these, about 70% are diagnosed with advanced NSCLC. In the US and Europe, approximately 10-15% of NSCLC patients 

The basis for the sNDA lies in data from the FLAURA2 Phase III trial, which was presented at the International Association for the Study of Lung Cancer (IASLC) 2023 World Conference on Lung Cancer (WCLC) in a Presidential Symposium. 

In this trial, combining TAGRISSO with chemotherapy demonstrated a 38% reduction in the risk of disease progression or death Median progression-free survival (PFS) was extended by 8.8 months according to investigator assessment. 

Results from blinded independent central review showed a 9.5-month extension in median PFS. The combination showed a clinically meaningful PFS benefit across various subgroups, including patients with central nervous system metastasis 

The trial continues to assess overall survival (OS) as a key secondary endpoint. Regarding safety, the combination of TAGRISSO plus chemotherapy had a generally manageable profile consistent with the established profiles of the individual medicines. 

Adverse event rates were higher in the combination arm due to known chemotherapy-related adverse events. 

In August 2023, TAGRISSO in combination with chemotherapy received Breakthrough Therapy Designation by the FDA for the 1st-line treatment of adult patients with locally advanced or metastatic EGFRm NSCLC. TAGRISSO is already approved as monotherapy in over 100 countries, including the US, EU, China, and Japan, for various indications related to EGFRm NSCLC

Cimeio Therapeutics and University of Pennsylvania Collaborate on CD45 CAR T Cell Therapy for Blood and Bone Marrow Cancers

Cimeio Therapeutics, a key player in the field of innovative therapeutics, has made a significant announcement regarding a preclinical research collaboration with the University of Pennsylvania. 

This collaboration, spearheaded by Saar Gill, M.D., Ph.D., an esteemed associate professor of medicine and a researcher at the University’s Center for Cellular Immunotherapies, aims to delve into the realm of universal immunotherapy. 

The objective is to create a potential treatment modality for various types of blood and bone marrow cancers. The collaboration capitalizes on the unique strengths of both entities, leveraging Cimeio Therapeutics’ proprietary epitope-editing and CD45-targeting technologies in tandem with Penn Medicine’s epitope-editing and CAR T cell technology. 

The ultimate goal is to design a revolutionary CD45-targeting CAR T cell therapy coupled with epitope-edited hematopoietic stem cells (HSCs). CD45, being prominently present on the surface of a wide array of blood cells, is a pivotal receptor that holds promise for the development of a universal CAR T cell therapy tailored for blood cancers. 

Recent breakthroughs in epitope editing have shown promise in effectively editing CD45, a receptor ubiquitously expressed on the surface of both healthy HSCs and numerous blood and bone marrow cancers. 

This collaboration builds upon the research and findings that have demonstrated the potential to shield healthy HSCs while making malignant cells susceptible to a CD45-targeting therapy, presenting a promising avenue for drug development. In addition to this groundbreaking research, Cimeio Therapeutics is advancing its efforts in the field by also working on the development of a CD45-directed antibody-drug conjugate. 

The company has a strategic vision to develop this therapy utilizing CD45 epitope shielded cells, not only for blood cancers but also for autoimmune diseases and various other indications.

Pfizer's VELSIPITY Granted FDA Approval for Moderate to Severe Active Ulcerative Colitis in Adults

 

Pfizer's VELSIPITY Granted FDA Approval for Moderate to Severe Active Ulcerative Colitis in Adults

Pfizer has received the green light from the U.S. Food and Drug Administration (FDA) for VELSIPITY, also known as etrasimod, an oral medication that is taken once daily and selectively modulates the sphingosine-1-phosphate (S1P) receptor.

 This approval is specifically for adults who are dealing with moderately to severely active ulcerative colitis (UC), a chronic and often disabling condition affecting an estimated 1.25 million individuals in the United States. 

The recommended dose for 2 mg Symptoms of UC can be distressing and encompass chronic diarrhea with blood and mucus, abdominal pain, and a compelling sense of urgency, and the impact goes beyond the physical aspect due to the chronic and unpredictable nature of the symptoms. 

 The FDA approval was grounded on the promising outcomes of the ELEVATE UC Phase 3 registrational program, specifically the ELEVATE UC 52 and ELEVATE UC 12 trials. These trials evaluated the safety and efficacy of VELSIPITY 2 mg once daily in inducing clinical remission among UC patients who had previously failed or were intolerant to at least one conventional treatment, biologic, or Janus kinase (JAK) inhibitor therapy. Notably, a significant proportion of patients in these trials were treatment-naïve to biologic or JAK inhibitor therapy. 

The studies achieved all primary and key secondary efficacy endpoints, while maintaining a safety profile consistent with previous VELSIPITY studies. 

 In the ELEVATE UC 52 trial, patients treated with VELSIPITY demonstrated a substantial increase in clinical remission rates compared to those on placebo at both week 12 and week 52. at both week 12 and week 52 Similarly, in the ELEVATE UC 12 trial, a noteworthy proportion of patients on VELSIPITY achieved clinical remission compared to the placebo group at week 12. These findings, along with positive outcomes in key secondary endpoints like endoscopic improvement and mucosal healing, substantiated the efficacy of VELSIPITY in treating UC. VELSIPITY represents a significant advancement as a once-daily, oral medication that selectively binds with specific S1P receptor subtypes. 

Regulatory applications for VELSIPITY's approval in treating ulcerative colitis have been submitted in various countries worldwide, including Canada, Australia, Mexico, Russia, Switzerland, and Singapore. The European Medicines Agency (EMA) has accepted the Marketing Authorization Application (MAA) for VELSIPITY, and a decision from EMA is expected in the early months of 2024. 

The pivotal ELEVATE UC 52 trial was designed with a 12-week induction period followed by a 40-week maintenance period, employing a randomized, double-blind, placebo-controlled approach. The primary goal was to assess the safety and efficacy of etrasimod 2 mg once daily on clinical remission after both 12 and 52 weeks. The trial demonstrated significant improvements in primary and key secondary endpoints, including endoscopic improvement and mucosal healing. 

 Similarly, the ELEVATE UC 12 trial, which was also randomized and placebo-controlled, focused on assessing the efficacy and safety of etrasimod 2 mg once daily in subjects with moderately to severely active UC. The trial achieved its primary objective, showcasing a noteworthy proportion of patients achieving clinical remission with etrasimod compared to the placebo group at week 12 at week 12 

Importantly, the safety profile of VELSIPITY was consistent across both trials, with common adverse reactions being manageable and not unexpected. These trials affirm that initiating VELSIPITY treatment does not necessitate a complex up-titration regimen, enhancing its practicality and ease of use for patients

US FDA Approves Encorafenib & Binimetinib for Metastatic Lung Cancer Patients with BRAF V600E Mutation

 

Bayer Unveils Pioneering Cell Therapy Hub, Revolutionizing Global Regenerative Medicine

 

FDA approves encorafenib with binimetinib for metastatic non-small cell lung cancer with a BRAF V600E mutation

On October 11, 2023, the Food and Drug Administration (FDA) granted approval for the use of encorafenib (Braftovi, developed by Array BioPharma Inc., a subsidiary of Pfizer) in combination with binimetinib (Mektovi, also by Array BioPharma Inc.) for adult patients dealing with metastatic non-small cell lung cancer (NSCLC) characterized by a BRAF V600E mutation, as confirmed by an FDA-endorsed diagnostic test.

In conjunction with this approval, the FDA also sanctioned the utilization of FoundationOne CDx (tissue) and FoundationOne Liquid CDx (plasma) as companion diagnostics for encorafenib with binimetinib. It was emphasized that in cases where no mutation is detected in a plasma sample, a test should be conducted on tumor tissue.

The assessment of efficacy encompassed 98 patients grappling with metastatic NSCLC and possessing the BRAF V600E mutation. These patients were enrolled in the PHAROS study (NCT03915951), which was an open-label, multicenter, single-arm study. Notably, patients were not allowed to have had prior exposure to BRAF or MEK inhibitors. Patients received a regimen of encorafenib and binimetinib until either their disease progressed or they experienced unacceptable levels of toxicity.

The primary efficacy outcomes were gauged by the objective response rate (ORR) per RECIST v1.1 and the duration of response (DoR), as evaluated by an independent review committee. Out of 59 patients who were new to treatment, an ORR of 75% was observed (95% CI: 62, 85), with an indeterminate median DoR (NE) (95% CI: 23.1, NE). Among the 39 patients who had previously undergone treatment, an ORR of 46% was noted (95% CI: 30, 63) along with a median DoR of 16.7 months (95% CI: 7.4, NE).

The adverse reactions most frequently reported (≥25%) were fatigue, nausea, diarrhea, musculoskeletal pain, vomiting, abdominal pain, visual impairment, constipation, dyspnea, rash, and cough.

In terms of recommended doses for NSCLC patients positive for the BRAF V600E mutation, the guidance stipulates an oral administration of encorafenib at 450 mg once daily and binimetinib at 45 mg orally twice daily.

This comprehensive review of the application incorporated the Assessment Aid, a voluntary submission from the applicant intended to streamline the FDA's evaluation. Additionally, the application was granted orphan drug designation, underlining the significance and unique status of this therapeutic approach.