Latest news with #phase2trial
Medscape
05-08-2025
- Health
- Medscape
Orforglipron: A Pill Alternative to GLP-1 Injections
This transcript has been edited for clarity. Orforglipron is a once-daily, oral, nonpeptide GLP-1 receptor agonist currently under investigation for the treatment of both obesity and type 2 diabetes. The most recent weight management data come from a phase 2 trial of 272 adults with a BMI over 30, or over 27 and at least one weight-related medical condition, but without received daily orforglipron at one of four doses or placebo for 36 weeks. The average baseline BMI was 37.9. At 36 weeks, participants on the highest dose of orforglipron (45 mg) lost an average of 14.7% of their total body weight compared to 2.3% with placebo. Weight loss of at least 10% occurred in 46% to 75% of participants on orforglipron versus 9% on placebo, and 48% of participants on 45 mg lost 15% or more of their total body weight. It's important to note that this trial was only 36 weeks long and that weight loss had not yet plateaued, which suggests the possibility of additional weight loss with longer treatment. There were also improvements in weight-related and cardiometabolic parameters. The most common side effects were mild to moderate [gastrointestinal] symptoms, which mainly occurred during dose the safety profile of orforglipron was consistent with that of the other GLP-1 receptor agonists. Orforglipron is currently in phase 3 ATTAIN trials for obesity, with results expected in late 2025. Eli Lilly plans to seek FDA approval for weight management by the end of 2025. If approved, orforglipron would offer an oral, incretin-based alternative with efficacy potentially similar to the injectable GLP-1s, helping to improve treatment adherence and access. Top-line results from the phase 3 ACHIEVE-1 trial for orforglipron for type 2 diabetes were published in April. The full results were presented at the [American Diabetes Association] conference in June and published soon after. Eli Lilly expects to submit for approval for the treatment of type 2 diabetes in 2026.
Medscape
16-06-2025
- Health
- Medscape
Avelumab Plus Axitinib Shows Promise in Advanced GIST
Combination therapy with avelumab plus axitinib demonstrated a clinical benefit in patients with advanced gastrointestinal stromal tumour (GIST), achieving a 69.6% disease control rate and a 57.1% progression-free survival (PFS) rate at 3 months. METHODOLOGY: Researchers conducted a phase 2 trial to evaluate the safety and efficacy of avelumab in combination with axitinib among 56 patients with unresectable/metastatic GIST (median age, 60 years) after the failure of standard therapy. Participants received avelumab 10 mg/kg intravenously every 2 weeks combined with axitinib 5 mg orally twice daily. The primary endpoint was the 3-month PFS rate; key secondary endpoints included overall survival, disease control rate, duration of response, and adverse events (AEs). The median follow-up duration was 27.4 months. TAKEAWAY: The PFS rate at 3 months was 57.1%, the median PFS was 4.6 months, and the median overall survival was 14.2 months. A partial response was achieved in 8.9% of patients, and the median duration of response was 18.5 months. Stable disease was observed in 60.7% of patients, corresponding to a disease control rate of 69.6%. AEs occurred in 94.6% of patients, with 30.4% experiencing grade 3 or higher events. The most common treatment-related AEs were diarrhoea (33.9%), thyroid dysfunction (30.4%), hypertension (25%), palmar-plantar erythrodysesthesia (23.2%), myalgia (17.9%), and dysphonia (17.9%). IN PRACTICE: "The AXAGIST trial is the largest prospective study evaluating the efficacy of the combination of immune checkpoint inhibitor and a multikinase inhibitor in patients with advanced/metastatic GIST. These results provide unique data on the activity of axitinib in GIST patients, which in combination with avelumab, resulted in long-term clinical benefit in a significant subset of patients," the authors wrote. SOURCE: This study was led by Piotr Lukasz Rutkowski, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland. It was published online on June 06, 2025, in the European Journal of Cancer . LIMITATIONS: This study lacked a comparator arm, which made it impossible to conclude whether the addition of avelumab improves the antitumour activity of axitinib. DISCLOSURES: This research and drug supply were financially supported by Pfizer, as part of an alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc. Several authors declared receiving honoraria or having other ties with various sources.
Medscape
06-06-2025
- Health
- Medscape
Experimental MS Drug Nearly Eliminates Disease Activity
PHOENIX — Frexalimab, a second-generation anti-CD40 ligand monoclonal antibody provides extended tight control of multiple sclerosis (MS) whether measured by relapse or brain imaging at 2-year follow-up, results of an open-label extension (OLE) of a phase 2 trial showed. 'At week 96, there was almost complete suppression of new gadolinium-enhancing lesions with very similar pattern seen with new or enhancing T2 lesions,' said study investigator Stephen Krieger, MD, professor of neurology, Icahn School of Medicine at Mount Sinai, New York City. Two phase 3 international studies with this drug are already enrolling. 'Part of the interest in frexalimab and anti-CD40 therapies is the idea that one can modulate both B- and T-cell activity without cell depletion,' explained Krieger, who presented the long-term open-label data on May 29 at the Consortium of Multiple Sclerosis Centers (CMSC) 2025 Annual Meeting. Near Complete Disease Suppression The latest data suggest frexalimab is fulfilling its promise. Over follow-up to date, there has been nearly complete suppression of gadolinium-enhancing (Gd+) lesions on MRI among those taking the dose now being tested in the phase 3 trials. At 2 years, with an annualized relapse rate of 0.08%, 92% of patients were relapse-free. The randomized portion of this phase 2 trial attracted attention when it was published a year ago in The New England Journal of Medicine , but the 2-year results showed that the efficacy and safety observed at 12 weeks persist. In the controlled trial, 129 patients with relapsing MS were randomized to 300-mg, 400-mg, 600-mg, or 1200-mg frexalimab or matching placebos. Suppression of Gd+ lesions was the primary endpoint. At 12 weeks, the adjusted mean of new Gd+ lesions was 1.4 in the combined placebo groups but 0.3 in the 300-mg frexalimab group and 0.2 in the 1200-mg group. Of those who participated in the randomized portion of the phase 2 trial, 97% continued into the long-term OLE. The OLE consisted of two arms: 1200-mg frexalimab administered intravenously every 4 weeks or 300-mg frexalimab administered subcutaneously every 2 weeks. At the end of 2 years, when 82% of those enrolled in the OLE were still on medication, the adjusted mean for new T1-weighted Gd+ lesions ranged from 0.1 to 0.3 across study arms whether on continuous frexalimab or switched from placebo to frexalimab. For those who were initiated on the 1200-mg dose in the controlled portion of the trial and remained on this dose for the OLE, the mean was 0.1. For the secondary endpoint of new or enlarging T2 lesions, the suppression at 2 years was almost the same. Again, the adjusted mean for new lesions across all arms ranged from 0.1 to 0.3. For those receiving the 1200-mg dose, the mean was 0.2. Mean T2 lesion volume increased in the placebo arm but not in the treatment arms during the randomized phase. After entering the OLE, T2 lesion volume fell in placebo patients now on active therapy. In the 1200-mg arm, the fall in lesion volume during the randomized phase continued into the first 24 weeks of the OLE. After 24 weeks, the lesion volume remained suppressed with no return toward baseline. Those initiated on placebo never caught up after switching to frexalimab. Relapse Rare — 2% at 96 Weeks On the 1200-mg dose of frexalimab, only 8% had any relapse recorded over the extended follow-up. In half, there was a single relapse. Only 2% had three or more relapses. While the Expanded Disability Status Scale score declined slightly among placebo patients once started on active therapy, there was no change from baseline through 96 weeks in patients started on any active therapy. As postulated by earlier preclinical and clinical studies, frexalimab had no effect on lymphocyte counts over time. Over the 96-week follow-up, levels of immunoglobulins remained unchanged, according to Krieger who showed graphs with straight lines for these values over the course of the OLE. Due to the potential of suppressing activation of both T and B cells over time, anti-CD40 therapies have long been considered a promising mechanism for control of MS. However, clinical development of first-generation drugs was abandoned because of an association with thromboembolism. 'Frexalimab has been engineered to avoid these events through a change in the Fc receptors with reduces downstream inflammatory events,' said Krieger. The long-term data support this premise. Over 2 years, there was one pulmonary embolism, but this exception was observed in a patient with a viral illness and a genetic predisposition for an inflammatory response, according to Krieger. When surveying other adverse events, 'nothing jumps out' in the OLE relative to the randomized phase. One potential exception is a rise in liver function tests observed in two (4%) patients on the 1200-mg dose. Only one of these patients discontinued therapy, and the levels returned to normal over time in both. The effects of the anti-CD40 mechanism on both the adaptive and innate immune systems suggest frexalimab might offer efficacy for both progressive and relapsing MS. In the ongoing phase 3 program, one of the trials (FREXALT) is enrolling patients with relapsing MS. The other (FREVIVA) is enrolling patients with progressive disease. Fulfilling its Promise Commenting on the results, Amit Bar-Or, MD, Chief of the Multiple Sclerosis Division, the Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, described frexalimab as 'a very interesting drug.' He agreed that the CD40 ligand is a promising target in MS but cautioned that these phase 2 data cannot answer the most interesting questions. This includes the more robust evidence of safety and efficacy from phase 3 trials, but it remains unclear whether the benefits extend beyond controlling relapsing disease. 'I think there is particular interest in whether it will also show extended benefit in progressive MS, and this will be a major focus of interest from the next set of studies,' Bar-Or said.
