The proportion of patients achieving the targeted reduction in spleen volume as measured by magnetic resonance imaging or computed tomography was the primary endpoint of LIMBER-304. Secondary endpoints included the proportion of patients who had a targeted reduction in Total Symptom Score (TSS), the change in TSS, the time to the first 50% reduction in TSS, overall survival, the number of treatment-emergent adverse events, the time of onset of the targeted reduction in spleen volume, and the duration of maintenance of the targetted reduction in spleen volume.
FDA Sets July Verdict Date for Eisai and Biogen‘s Leqembi
Eisai Co., Ltd. and Biogen Inc. announced that the FDA had accepted Eisai’s supplemental Biologics License Application (sBLA) for LEQEMBI (lecanemab-irmb) 100 mg/mL injection for intravenous use, paving the way for LEQEMBI’s accelerated approval to be converted to a traditional approval. The LEQEMBI application has been granted Priority Review, with an action date of July 6, 2023, under the Prescription Drug User Fee Act (PDUFA). The FDA is currently planning an Advisory Committee meeting to discuss this application but has not yet publicly announced the date.
LEQEMBI is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibrils*) and insoluble forms of amyloid beta (A) that was approved under the Accelerated Approval Pathway on January 6, 2023, for the treatment of Alzheimer’s Disease (AD). LEQEMBI treatment should be initiated only in patients with mild cognitive impairment or mild dementia and the presence of A pathology. On the same day that LEQEMBI received accelerated approval, Eisai submitted the sBLA to the FDA for traditional approval.
The sBLA is based on the findings of Eisai’s recently published large, global confirmatory Phase III clinical trial, Clarity AD. LEQEMBI met the primary endpoint and all key secondary endpoints with highly statistically significant results. The results of the Clarity AD study were presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference in November 2022 and simultaneously published in the peer-reviewed medical journal, The New England Journal of Medicine.
LEQEMBI received accelerated approval in the United States and was launched on January 18, 2023. The accelerated approval was based on Phase II data demonstrating that LEQEMBI reduced the accumulation of A plaque in the brain, a defining feature of AD, and its continued approval may be contingent on confirmation of LEQEMBI’s clinical benefit in a confirmatory trial. The FDA has determined that the results of Clarity AD can be used as a confirmatory study to verify the clinical benefit of lecanemab. Eisai is the global lead for LEQEMBI development and regulatory submissions, with Eisai and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making authority.
FDA Approves Reata Pharmaceuticals’ SKYCLARYS for Friedreich’s ataxia
Reata Pharmaceuticals declared that the U.S. Food and Drug Administration had approved SKYCLARYS for treating Friedreich’s ataxia in adults and adolescents aged 16. With this approval, the FDA awarded a priority review voucher for rare pediatric diseases.
MOXIe Part 2 was a randomized, double-blind, placebo-controlled study. Patients with genetically confirmed Friedreich’s ataxia and baseline-modified Friedreich’s Ataxia rating scale scores between 20 and 80 were randomized 1:1 to receive a placebo or 150 mg of SKYCLARYS daily. The primary endpoint was a change from baseline in mFARS score compared to placebo at week 48 in the full analysis population of patients without severe pes cavus. The mFARS is a clinical assessment tool to assess patient function and is used in clinical trials to evaluate the efficacy of investigational products for use in Friedreich’s ataxia.
At week 48, treatment with SKYCLARYS led to a statistically significant decrease in mFARS scores compared to the placebo group. After adjusting for the placebo, the difference between the two groups was -2.41 points, with a p-value of 0.0138. The most frequently reported adverse reactions in MOXIe Part 2 were elevated liver enzymes, headache, nausea, abdominal pain, fatigue, diarrhea, and musculoskeletal pain.
Furthermore, a post hoc propensity-matched analysis was conducted to compare the mFARS progression of patients who received a daily dose of 150 mg of SKYCLARYS in the open-label MOXIe extension trial with propensity score-matched untreated patients in the most comprehensive natural history study of friedreich’s ataxia, clinical outcome measures in friedreich’s ataxia. All patients who participated in the MOXIe Extension study and had at least one post-baseline evaluation were matched with patients from the FA-COMS study. After three years, patients treated with SKYCLARYS showed lower (improved) mFARS scores compared to the matched group of untreated patients from the FA-COMS natural history study. These analyses are exploratory and should be interpreted with caution due to the limitations of data collected outside of a controlled study, which may be subject to confounding.
Temferon Lands FDA Orphan Drug Status for Glioblastoma Multiforme
Genenta Science declared that the U.S. Food and Drug Administration had granted Orphan Drug Designation to Temferon for treating glioblastoma multiforme.
Temferon is a distinctive cell therapy developed to reprogram the tumor microenvironment by providing immunomodulatory molecules directly to tumors. Genenta is evaluating Temferon in an ongoing Phase 1/2a clinical trial, focusing on newly diagnosed patients with GBM with an unmethylated MGMT gene promoter.
Around 60% of the GBM population is identified to have an unmethylated MGMT promoter status. GBM is recognized as the most prevalent malignant primary brain tumor and the most aggressive diffuse glioma.
The ODD program aims to promote the development of treatments for diseases that impact fewer than 200,000 individuals in the United States. Benefits associated with the designation include eligibility for federal grants, tax credits for qualified clinical trials, prescription drug user fee exemptions, and a seven-year marketing exclusivity period upon FDA approval.
Harbour BioMed Announces Positive Topline Results from Phase III Trial of Batoclimab for Treatment of Generalized Myasthenia Gravis
On March 6, 2023, Harbour BioMed announced the positive topline results of its phase III clinical trial evaluating batoclimab (HBM9161) for the treatment of generalized myasthenia gravis (gMG). It is also the first positive pivotal trial outcome for batoclimab worldwide.
The clinical study aimed to confirm the efficacy and safety of batoclimab in patients with gMG in China. Data received from the phase III trial met the primary endpoint as well as key secondary endpoints. Meanwhile, batoclimab treatment was overall safe and well-tolerated, and no new safety signal was identified.
Harbour BioMed’s Batoclimab is a fully human anti-FcRn mAb, blocks FcRn-IgG interactions, accelerating the degradation of autoantibodies and leading to the treatment of pathogenic IgG-mediated autoimmune diseases. Phase 2 study in myasthenia gravis showed that batoclimab can quickly and significantly alleviate patients’ symptoms and improve quality of life. Earlier studies demonstrated that batoclimab is well tolerated and can rapidly reduce total IgG in many pathogenic IgG-mediated autoimmune diseases.
Dr. Jingsong Wang, Founder, Chairman and CEO of Harbour BioMed has said, “this breakthrough therapy represents a significant advance in the treatment of multiple pathogenic-IgG mediated autoimmune diseases, where there remains a significant unmet medical need such as gMG indication.”
Earlier in early 2021, Batoclimab received the “Breakthrough Therapy Certificate” from NMPA and subsequently received a positive outcome of the proof-of-concept study for the treatment of Chinese gMG patients completed in August 2021. In October 2022, the Company entered into an agreement with NBP Pharma, a wholly owned subsidiary of the CSPC Group, to co-develop batoclimab in Great China. The Company was responsible for developing and operating the full clinical trial of batoclimab for gMG in China and will receive tiered royalties based on annual net sales of batoclimab in Greater China according to the agreement.
Ikena Oncology Receives FDA Fast Track Designation for Novel AHR Antagonist IK-175 in Combination with Nivolumab to Treat Urothelial Carcinoma
On March 06, 2023, Ikena Oncology, Inc. announced that the US FDA had granted Fast Track designation for IK-175, the Company’s novel aryl hydrocarbon receptor (AHR) antagonist, in combination with immune checkpoint inhibitors in patients with advanced urothelial carcinoma who have progressed on or within three months of receiving the last dose of checkpoint inhibitors. Ikena’s IK-175 targets AHR, a compelling cancer-driving transcription factor that prevents immune recognition in a multitude of cancers by modulation of innate and adaptive immunity. The IK-175 program is being developed in collaboration with Bristol Myers Squibb, and they have an option to exclusively license the program through early 2024.
On achieving the significant milestone, Sergio Santillana, MD, Chief Medical Officer, Ikena has said, “there is an urgent need for new treatment options for urothelial carcinoma patients, many of whom find themselves out of options after progressing on checkpoint inhibitors. The Fast Track designation for IK-175 reflects the FDA’s interest in the potential role of our AHR antagonist to overcome the development of resistance to checkpoint inhibitors and supports our strategy of combining IK-175 with nivolumab to expand the number of cancer patients that can benefit from immunotherapy,”.
IK-175 is currently being studied in a Phase 1a/b clinical trial as a monotherapy and in combination with nivolumab in patients with advanced or metastatic solid tumors, including urothelial carcinoma for which standard therapy is no longer effective or is intolerable (NCT04200963, or IK-175-001).
According to the data Initial clinical data presented at the Society for Immunotherapy of Cancer (SITC) 2022 Annual Meeting, IK-175 is well tolerated and showed encouraging, durable, antitumor activity in stage 1 of the trial’s monotherapy and combination arms in urothelial carcinoma patients. As per the update from Ikena Oncology, IK-175 is the company’s second candidate to receive Fast Track designation; the FDA has also granted the designation to IK-930, the Company’s novel TEAD inhibitor, in patients with unresectable NF2-deficient malignant pleural mesothelioma.
