Bayer Phase III NSCLC Trial; D&D Pharmatech Gets FDA Nod for GLP-1R Agonist in Multiple Scletosis; Merck Halts Two KEYTRUDA Trials; Novartis Expands LEQVIO After Phase III Success; Alnylam Reports Strong Phase III Data for Vutrisiran

Bayer Starts Phase III Trial In Non-Small Cell Lung Cancer (NSCLC)

Bayer has officially enrolled the first patient in the global Phase III SOHO-02 trial, which will evaluate the efficacy and safety of BAY 2927088 as a first-line treatment for advanced non-small cell lung cancer (NSCLC) with activating HER2 mutations. This open-label, randomized, multicenter trial is a crucial step in Bayer’s ongoing efforts to address the unmet needs of patients with this aggressive form of lung cancer.

In addition to the SOHO-02 trial, BAY 2927088 is under investigation as a second-line therapy for adults with unresectable or metastatic NSCLC harboring HER2 (ERBB2) mutations. Results from the Phase I/II SOHO-01 trial will be unveiled at the World Conference on Lung Cancer (WCLC) on September 9th, 2024. “Our commitment to precision medicine is not just a promise but a mission to address the critical unmet needs of individuals battling HER2-mutant NSCLC,” said Christian Rommel, Ph.D., Head of R&D at Bayer’s Pharmaceuticals Division.

Derived from Bayer’s partnership with the Broad Institute of MIT and Harvard, BAY 2927088 has already earned Breakthrough Therapy designation from both the FDA and China’s Center for Drug Evaluation. This highlights its potential as a significant advancement in treating HER2-mutant NSCLC, a condition with limited targeted therapy options.

D&D Pharmatech Secures FDA Approval for Phase II Trial of GLP-1R Agonist in Multiple Sclerosis

D&D Pharmatech, a Korean biotech firm, has received FDA approval to begin a Phase II clinical trial of its experimental drug, NLY01, for multiple sclerosis. This trial, led by Johns Hopkins University’s Multiple Sclerosis Center, will evaluate NLY01’s potential to slow neurodegeneration in MS patients. 

“The primary objective is to assess whether NLY01 reduces imaging biomarkers related to neurodegeneration in MS patients,” stated a D&D Pharmatech official.

NLY01, a GLP-1 receptor agonist, has previously shown promise in a Phase II trial for Parkinson’s disease, demonstrating its potential as a disease-modifying treatment. The new trial will involve 240 patients over 96 weeks, focusing on MS patients aged 18 to 60, a group that showed notable therapeutic benefits in prior studies. “The FDA’s approval reflects the significant disease-modifying effects we observed in younger patients during our Parkinson’s trial,” said D&D Pharmatech CEO Lee Seul-ki.

The trial has attracted attention from global organizations, including the International Progressive MS Alliance, which is considering funding the study. Additionally, D&D Pharmatech has been invited to apply for support through the NIH’s NeuroNEXT program, which could further accelerate the trial process.

Merck Halts Two KEYTRUDA Phase III Cancer Trials Following Unfavorable Results

Merck announced on Thursday that it is discontinuing two late-stage trials of its PD-1 inhibitor, KEYTRUDA (pembrolizumab), due to disappointing lung and skin cancer outcomes. The Phase III KEYNOTE-867 trial, which combined KEYTRUDA with stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC), was halted after an interim analysis showed no significant improvement in survival outcomes and higher rates of adverse events compared to the placebo. Merck stated that the benefit-risk profile of the KEYTRUDA regimen did not justify continuing the trial.

Similarly, the Phase III KEYNOTE-630 trial, which evaluated KEYTRUDA as an adjuvant therapy for high-risk locally advanced cutaneous squamous cell carcinoma (cSCC), was also terminated. An independent data monitoring committee recommended stopping the study after KEYTRUDA failed to meet the primary endpoint of recurrence-free survival. Merck noted that the overall survival figures did not favor KEYTRUDA either, reinforcing the decision to end the trial.

These recent trial discontinuations are the latest in a series of setbacks for KEYTRUDA, which has faced challenges in several clinical trials over the past months. Despite these hurdles, Merck will continue to analyze the data from these studies and plans to share its findings with regulatory authorities and the broader scientific community.

Novartis Plots LEQVIO Expansion After Lowering Cholesterol in Phase III Study

Novartis announced positive results from its Phase III V-MONO study, where LEQVIO (inclisiran) monotherapy met its primary endpoints by significantly reducing low-density lipoprotein cholesterol (LDL-C) compared to both placebo and ezetimibe. The trial focused on patients at low or moderate risk of atherosclerotic cardiovascular disease (ASCVD) and not receiving other lipid-lowering treatments, demonstrated the effectiveness of LEQVIO as a twice-yearly therapy.

The V-MONO study is the first to evaluate a small interfering RNA (siRNA) therapy as a standalone treatment for LDL-C reduction in this patient population. “This trial adds to the growing body of evidence for LEQVIO across the full spectrum of ASCVD as we strive to help more patients in need,” said Shreeram Aradhye, M.D., President, Development, and Chief Medical Officer at Novartis.

Novartis plans to present the V-MONO trial results at an upcoming medical meeting and share them with regulatory agencies, including the FDA. The study is part of the broader 60,000-patient VictORION clinical trial program, which is exploring LEQVIO’s potential in both primary and secondary ASCVD prevention.

Alnylam Builds ATTR-CM Case for Vutrisiran With Strong Phase III Survival Data

Alnylam Pharmaceuticals has reported positive results from its Phase III HELIOS-B study of vutrisiran, an investigational RNAi therapeutic for transthyretin amyloidosis with cardiomyopathy (ATTR-CM). The study, presented at the European Society of Cardiology (ESC) Congress 2024 and published in The New England Journal of Medicine, met all primary and secondary endpoints. Vutrisiran significantly reduced all-cause mortality and recurrent cardiovascular events by 28% in the overall population and 33% in the monotherapy population over the study period.

The trial also demonstrated a 31% reduction in mortality during the 33-36 month double-blind period and a 36% reduction up to 42 months in the overall population. In addition, vutrisiran showed consistent benefits across various clinical measures of disease progression, including the 6-Minute Walk Test and NT-proBNP levels, even in patients receiving background treatment with tafamidis.

“These results suggest that vutrisiran can dramatically reduce all-cause mortality and cardiovascular events in patients with ATTR-CM,” said Marianna Fontana, M.D., Ph.D., a HELIOS-B investigator and Professor of Cardiology at University College London. Pushkal Garg, M.D., Chief Medical Officer at Alnylam, added, “The data indicate that vutrisiran has the potential to become a new standard of care for ATTR-CM, and we are working urgently to bring this medicine to patients worldwide.”