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Japan Drug Approvals | March 2024 | PMDA | MHLW Updates | iPharmaCenter

  1. Approval of Truqap plus Faslodex Granted in Japan for Patients Dealing with Advanced Hormone Receptor-Positive Breast Cancer

  2. Beyfortus Receives Approval in Japan for RSV Disease Prevention in Infants

  3. Astellas Introduces Vyloy (zolbetuximab) for Gastric Cancer Treatment in Japan


Approval of Truqap plus Faslodex Granted in Japan for Patients Dealing with Advanced Hormone Receptor-Positive Breast Cancer

  • Unique AKT Inhibitor Receives Green Light in Japan for Breast Cancer Patients Carrying Specific Biomarker Modifications (PIK3CA, AKT1 or PTEN)

  • Authorization hinged on CAPItello-291 findings which unveiled Truqap plus Faslodex's ability to slash the jeopardy of disease advancement or demise by 50% in comparison to Faslodex solo within the biomarker-modified demographic

AstraZeneca's Truqap (capivasertib) coupled with Faslodex (fulvestrant) has been given the nod in Japan for managing adult patients grappling with inoperable or recurring hormone receptor (HR)-positive, HER2-negative breast cancer bearing PIK3CA, AKT1, or PTEN alterations subsequent to relapse post-endocrine therapy.

The approval by Japan's Ministry of Health, Labour, and Welfare (MHLW) hinged on data extracted from the CAPItello-291 Phase III study published in The New England Journal of Medicine. In the study, the amalgamation of Truqap and Faslodex led to a 50% reduction in the risk of disease progression or fatality versus Faslodex monotherapy in individuals harboring PI3K/AKT pathway biomarker mutations (median progression-free survival (PFS) 7.3 versus 3.1 months).

In 2022, Japan witnessed over 90,000 diagnoses of breast cancer, with over 17,000 succumbing to the ailment in the same year. On a global scale, hormone receptor-positive breast cancer (manifesting estrogen or progesterone receptors, or both) stands as the predominant subtype, with more than 65% of tumors being categorized as HR-positive and either HER2-low or HER2-negative. Collectively, mutations in PIK3CA, AKT1, and PTEN modifications are frequent, affecting approximately 50% of individuals grappling with advanced HR-positive breast cancer.

Endocrine therapies are commonly deployed in this scenario, frequently in conjunction with cyclin-dependent kinase (CDK) 4/6 inhibitors, yet some tumors develop resistance to these treatments, accentuating the necessity for additional combination strategies with endocrine therapy to prolong the duration before chemotherapy initiation. During the CAPItello-291 trial, the safety profile of Truqap plus Faslodex remained consistent with observations from prior trials assessing this pairing.

Furthermore, MHLW has sanctioned a companion diagnostic examination for identifying the pertinent alterations (PIK3CA, AKT1, and PTEN).


Beyfortus Receives Approval in Japan for RSV Disease Prevention in Infants

AstraZeneca and Sanofi's Beyfortus (nirsevimab), a prolonged monoclonal antibody, has gained approval in Japan for safeguarding against lower respiratory tract disease (LRTD) caused by respiratory syncytial virus (RSV) in all newborns, infants, and children facing their initial RSV season, and for averting RSV LRTD in newborns, infants, and children at risk of severe RSV infection entering their first or second RSV season. Beyfortus is expected to be accessible for the forthcoming 2024/25 RSV season, aligning with existing Japanese protocols.

Beyfortus stands as the premier preventative measure crafted to shield a wide spectrum of infantile populations against RSV LRTD, encompassing defense for healthy term newborns, preterm infants, or those with specific health conditions predisposing them to grave illness. The authorization by the Japanese Ministry of Health, Labour, and Welfare stems from three pivotal late-stage clinical trials of Beyfortus. Across all clinical parameters, a singular dose of Beyfortus exhibited uniform efficacy against RSV LRTD, spanning the entirety of a typical RSV season.

Each year in Japan, over 100,000 instances of RSV LRTD are recorded in infants, including those born healthy at term.

The Phase IIb (Trial 03) investigation was a randomized, placebo-controlled trial engineered to gauge Beyfortus's efficacy against medically attended Lower Respiratory Tract Infection (LRTI) up to 150 days post-dosage. Healthy preterm infants aged between 29 to under 35 weeks' gestational age were randomized (2:1) to receive a single 50mg intramuscular Beyfortus injection or placebo, irrespective of weight.

The dosing regimen for Beyfortus was delineated through further scrutiny of Phase IIb data and was subsequently employed in subsequent trials, entailing a singular 50mg dose for those weighing less than 5kg, or a singular 100mg dose for those weighing 5kg or more.

The MELODY Phase III exploration (Trial 04) was a randomized, double-blind, placebo-controlled endeavor spanning 21 countries, aimed at delineating Beyfortus's efficacy against medically attended LRTI up to 150 days post-dosage, compared to placebo, in healthy term and late preterm infants (35 weeks gestational age or more) embarking on their maiden RSV season.

The MEDLEY (Trial 05) constituted a Phase II/III, randomized, double-blind, Synagis (palivizumab)-controlled inquiry with the primary intent of evaluating Beyfortus's safety and tolerability in preterm infants under 35 weeks' gestational age and infants with congenital heart disease (CHD) and/or chronic lung disease of prematurity (CLD) eligible for Synagis. Between July 2019 and May 2021, a total of 925 infants entering their inaugural RSV season were randomized (2:1) in each of the preterm and CLD/CHD categories to receive Beyfortus or Synagis. A cohort of 262 children up to 24 months old from the CLD/CHD category continued participation in the trial for a second RSV season. Safety was gauged through adverse event monitoring up to 360 days post-dosage.

Findings from MELODY, MEDLEY Phase II/III, and Phase IIb trials affirm that a sole Beyfortus dose aids in shielding infants throughout their debut RSV season against RSV disease. This wide-ranging infant population encompasses healthy term, late preterm, and preterm infants, along with those with specific health conditions rendering them susceptible to severe RSV disease.


Astellas Introduces Vyloy (zolbetuximab) for Gastric Cancer Treatment in Japan

Vyloy has gained approval for utilization alongside chemotherapy for patients afflicted with human epidermal growth factor receptor 2 (HER2)-negative, CLDN18.2 positive, unresectable, advanced, or recurrent gastric cancer.

On March 26, 2024, Japan's Ministry of Health, Labour, and Welfare (MHLW) officially sanctioned Vyloy (zolbetuximab), an anti-claudin 18.2 (CLDN18.2) monoclonal antibody designated for patients grappling with CLDN18.2 positive, unresectable, advanced, or recurrent gastric cancer. Vyloy stands as the initial and sole CLDN18.2-targeted therapy to garner approval from any regulatory body globally.

Gastric cancer frequently eludes early detection, often diagnosed in advanced or metastatic stages owing to symptoms overlapping with more prevalent stomach ailments. Despite ongoing efforts to curb its prevalence, gastric cancer remains the third leading cause of cancer-related deaths in Japan, with 126,724 cases diagnosed in 2022.

The approval hinges on findings from the Phase 3 SPOTLIGHT and GLOW clinical trials, examining first-line treatment efficacy in patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma characterized by CLDN18.2 positive tumors. The SPOTLIGHT study scrutinized Vyloy plus mFOLFOX6 against placebo plus mFOLFOX6, while the GLOW study assessed Vyloy plus CAPOX against placebo plus CAPOX. Both trials notched their primary endpoint of progression-free survival (PFS) and a crucial secondary endpoint of overall survival (OS), with statistical significance in patients receiving VYLOY plus chemotherapy versus placebo plus chemotherapy.

Common treatment-emergent adverse events (TEAEs) ≥20% for VYLOY in conjunction with mFOLFOX6 or CAPOX included nausea, vomiting, decreased appetite, neutropenia, and weight loss. Adverse reactions encountered in clinical trials were managed through antiemetics, dose adjustments, and infusion rate modifications.

Approximately 38% of screened patients in both SPOTLIGHT and GLOW exhibited CLDN18.2 positive tumors. CLDN18.2 positivity is characterized by ≥75% of tumor cells manifesting moderate-to-strong membranous CLDN18 staining, validated by a pathologist or laboratory equipped with the approved in-vitro diagnostic agent or medical device. Astellas collaborated with Roche Diagnostics on the recently sanctioned Ventana CLDN18 (43-14A) RxDx Assay, an immunohistochemistry (IHC) companion diagnostic (CDx) test, to identify potential Vyloycandidates. Testing facilities will be accessible in Japan through various central laboratories, with plans for expansion to additional facilities in the future.

Astellas has submitted applications for Vyloy to regulatory authorities worldwide, with ongoing reviews.

The impact of this approval has already been factored into Astellas's financial projection for the current fiscal year ending March 31, 2024.



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