FDA Greenlights Moderna’s RSV Vaccine mRESVIA(R)

Moderna, Inc. has announced that the FDA has approved mRESVIA (mRNA-1345), an mRNA-based vaccine for respiratory syncytial virus (RSV), to protect adults aged 60 and over from lower respiratory tract infections caused by RSV. This approval, granted under a breakthrough therapy designation, represents Moderna’s second approved mRNA product.

“The FDA approval of our second product, mRESVIA, highlights the robustness and adaptability of our mRNA platform,” stated Stéphane Bancel, CEO of Moderna. “mRESVIA offers protection to older adults against severe RSV infection and is uniquely available in a pre-filled syringe, simplifying administration, saving time for vaccinators, and minimizing the risk of errors. This marks the first approval of an mRNA vaccine for a disease other than COVID-19. With mRESVIA, we are committed to addressing global public health challenges associated with infectious diseases, continuing to prioritize patient care.”

RSV is a highly contagious seasonal respiratory virus and a major contributor to lower respiratory tract infections and pneumonia, posing a significant health burden, especially among infants and older adults. Annually in the U.S., RSV leads to the hospitalization of about 60,000 to 160,000 older adults and results in 6,000 to 10,000 deaths in this age group. As per DelveInsight analysis, in 2023, total incident cases of RSV were 8.6 million in the 7MM and the US accounted for the majority of the cases i.e. ~56%.

The FDA’s approval of mRESVIA is supported by positive results from the Phase III ConquerRSV clinical trial, a global study involving around 37,000 adults aged 60 and older across 22 countries. The primary analysis, with a median follow-up of 3.7 months, demonstrated a vaccine efficacy of 83.7% (95.88% CI 66.0%, 92.2%) against RSV lower respiratory tract disease (LRTD). These findings were published in The New England Journal of Medicine. During the FDA review, a follow-up analysis of the primary endpoint was conducted, which included cases that began before but were confirmed after the primary analysis cut-off date. The follow-up results were consistent with the primary analysis, showing a vaccine efficacy of 78.7% (CI 62.9%, 87.8%), and these were included in the U.S. package insert. Additionally, a longer-term analysis indicated sustained protection against RSV LRTD with a median follow-up of 8.6 months.

Novartis Scemblix® Phase III Data Demonstrates Superior Efficacy and Safety Over Standard TKIs in Newly Diagnosed Adult CML

Novartis has announced encouraging outcomes from the pivotal Phase III ASC4FIRST trial, presented as a late-breaking abstract at the 2024 American Society of Clinical Oncology (ASCO) meeting. The study revealed that Scemblix® (asciminib) achieved higher major molecular response (MMR) rates at week 48 compared to investigator-selected standard-of-care (SoC) tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib, dasatinib, and bosutinib, as well as imatinib alone, in patients newly diagnosed with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). Additionally, Scemblix showed a numerical advantage in MMR at week 48 compared to second-generation (2G) TKIs (nilotinib, dasatinib, and bosutinib). Moreover, Scemblix exhibited a favorable safety and tolerability profile, with fewer adverse events (AEs) and treatment discontinuations compared to both imatinib and 2G TKIs.

“Prof. Tim Hughes, MD, from the South Australian Health & Medical Research Institute (SAHMRI), highlighted that Scemblix stands out as the initial CML therapy demonstrating notably improved effectiveness compared to standard-of-care TKIs chosen by investigators. He emphasized the promising prospect of Scemblix as a frontline treatment for newly diagnosed patients due to its superior response rates and favorable safety and tolerability profile, potentially aiding patients in reaching their treatment objectives.”

The median duration of observation was 16.3 months for Scemblix and 15.7 months for standard-of-care TKIs chosen by investigators. Scemblix treatment resulted in approximately 20% more patients reaching Major Molecular Response (MMR) by week 48 compared to those on investigator-selected standard-of-care TKIs, and almost 30% more compared to those on imatinib alone. Additionally, patients on Scemblix achieved higher rates of molecular responses (MR4 and MR4.5) compared to those on investigator-selected standard-of-care TKIs and imatinib alone.

The trial is still in progress, with the next planned assessment at week 96 to assess the main secondary endpoint (MMR at week 96) and other secondary measures. These findings have been sent to the FDA through the Oncology Center of Excellence Real-Time Oncology Review (RTOR) program, leading to Scemblix receiving Breakthrough Therapy Designation. Additionally, they will be showcased as a keynote presentation at the European Hematology Association (EHA) 2024 Congress in June.

Kite’s Tecartus® Shows Long-Term Survival Benefits in Adults With Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia

Kite has revealed updated, extended survival data spanning four years from the pivotal ZUMA-3 trial, which investigates Tecartus® (brexucabtagene autoleucel) CAR T-cell therapy in adults with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). The data indicates a median overall survival (OS) of 25.6 months and a four-year OS rate of 40% (with a confidence interval of 95% ranging from 28% to 52%) across all treated patients, with a safety profile consistent with previous observations from the three-year analysis. These findings were shared through a poster presentation (Abstract #6531) at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

“B-cell acute lymphoblastic leukemia, a rare and aggressive blood cancer with a typically grim prognosis – with a median survival of under eight months in relapsed or refractory cases – makes the survival of 40% of such patients treated with a single infusion of Brexu-cel for four years noteworthy,” explained Olalekan O. Oluwole, MBBS, MD, MPH, Associate Professor of Medicine, Hematology/Oncology at Vanderbilt University and lead investigator of the study. “Moreover, the study revealed sustained response and survival benefits irrespective of whether patients underwent subsequent allogeneic stem cell transplantation.”

The presented poster details findings from a study where patients received the pivotal dose of Tecartus across Phases I and II, totaling 78 individuals. The median follow-up duration was 53.6 months, ranging from 44.7 to 82.3 months, with a minimum follow-up of 4 years. Among all participants, the median overall survival (OS) was 25.6 months. For those achieving complete remission or complete remission with incomplete hematologic recovery (n=57), which was the primary endpoint, the median OS extended to 47 months.

In subgroup analyses, patients younger than 26 years (n=15) had a median OS of 23.2 months (95% CI: 9.0-NE), while those aged 26 years or older (n=63) had a slightly longer median OS of 26.0 months (95% CI: 15.9-NE), with OS being a significant secondary endpoint.

Furthermore, among patients with one prior therapy (n=15), the median OS was notably longer at 60.4 months (95% CI: 7.6-NE) compared to those with two or more prior therapies (n=63), where the median OS was 25.4 months (95% CI: 15.9-47.0).

Astellas Resubmits Biologics License Application for Zolbetuximab, FDA Sets New Review Timeline

Astellas Pharma Inc. has announced that the FDA has recognized the company’s renewed submission of the Biologics License Application (BLA) for zolbetuximab. Zolbetuximab is a groundbreaking monoclonal antibody targeting claudin (CLDN) 18.2, intended for initial treatment in adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors test positive for CLDN18.2. If zolbetuximab is approved, it will mark the first CLDN18.2-targeted therapy authorized for this patient group in the United States. The FDA has established a new target action date of November 9, 2024, under the Prescription Drug User Fee Act (PDUFA).

“Astellas is dedicated to bringing forth innovative targeted treatments for challenging cancer types. Many individuals battling advanced gastric or GEJ cancer encounter significant gaps in available therapies. The FDA’s recognition of the zolbetuximab BLA resubmission signifies progress towards providing this crucial treatment option to eligible patients in the U.S. grappling with this life-threatening illness.” 

Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Senior Vice President and Head of Immuno-Oncology Development, Astellas

The application for zolbetuximab was re-submitted on May 9, 2024, after the FDA issued a complete response letter on January 4, 2024. This letter was prompted by manufacturing issues identified during a facility inspection by a third party before licensing. Importantly, the FDA did not express any worries regarding the effectiveness or safety of zolbetuximab based on clinical data, nor did they ask for further clinical trials to support the application’s approval.

On March 26, 2024, Japan’s Ministry of Health, Labour and Welfare (MHLW) gave its approval to zolbetuximab, marking it as the initial and solitary treatment focused on CLDN18.2 to gain approval for patients with CLDN18.2 positive, unresectable, advanced, or recurrent gastric cancer. Astellas has also lodged applications for zolbetuximab with regulatory bodies globally, with evaluations currently underway. The impact of the FDA’s recognition of the BLA resubmission for zolbetuximab has already been factored into Astellas’ financial projections for the current fiscal year ending March 31, 2025.

The CHMP Recommends the Approval of Tagrisso Combined with Chemotherapy for Patients with Advanced EGFR-mutated Lung Cancer in the EU

A recommendation has been made for the approval of AstraZeneca’s Tagrisso (osimertinib) in the European Union for first-line treatment of adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) that has specific mutations in the epidermal growth factor receptor (EGFR). This recommendation includes the addition of pemetrexed and platinum-based chemotherapy.

The favorable assessment by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) was founded on the findings of the FLAURA2 Phase III trial, which were likewise documented in The New England Journal of Medicine.

The findings indicated that combining chemotherapy with Tagrisso decreased the risk of disease advancement or mortality by 38% compared to using Tagrisso alone, which is the established initial treatment globally (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.49-0.79; p<0.0001). According to evaluations by investigators, the median period without progression of the disease (progression-free survival or PFS) was 25.5 months for patients receiving Tagrisso alongside chemotherapy, representing an improvement of 8.8 months compared to those on Tagrisso alone (16.7 months).

Though the data for overall survival (OS) is still preliminary (with only 41% of the expected events occurring), there was a promising indication of enhanced OS when Tagrisso was combined with chemotherapy compared to Tagrisso alone (HR 0.75; 95% CI 0.57-0.97). The trial is ongoing to further evaluate OS as an important secondary measure.

Tagrisso has been authorized for standalone use in over 100 nations worldwide, including the US, EU, China, and Japan. Its approved uses cover various scenarios, such as being the initial treatment option for individuals with locally advanced or metastatic EGFRm NSCLC, addressing EGFR T790M mutation-positive NSCLC in both advanced and early stages, and providing adjunctive therapy for early-stage EGFRm NSCLC. Additionally, in the US and numerous other nations, Tagrisso, when combined with chemotherapy, is endorsed as a first-line treatment for those with locally advanced or metastatic EGFRm NSCLC.