2025-05-12 於2025月05月12日

Once Every 5 Years Zoledronate Infusion Prevents Morphometric Fractures in Early Postmenopausal Women

Date: January 16, 2025

Persistent decrease in bone mineral density due to hormonal changes is nearly inevitable among postmenopausal women. The physiological change is also noted to be inversely related to fracture risk. Clinically approved fracture-prevention strategies mainly focus on groups with high-risk of fracture: elderly, osteoporotic patients and those with previous fractures. Zoledronate infusion is known to reduce the incidence of fractures among osteopenic and osteoporotic patients, with a prolonged duration of effect.

The 10-year, prospective, double-blind, randomized and placebo-controlled trial in New Zealand recruited 1054 women at their early postmenopausal period (50 to 60 years of age) with bone mineral density T scores between 0 and -2.5. Participants were assigned in a 1:1:1 ratio to receive (1) 5 mg zoledronate infusion at baseline and 5 years later (n=352), (2) 5 mg zoledronate infusion at baseline and normal saline as placebo 5 years later (n=351), and (3) normal saline infusions for both periods (n=351). The primary end point was the presence of new morphometric vertebral fracture in spinal radiographs. Fractures occurring in other body parts, changes in bone mineral density and bone turnover markers were regarded as secondary end points.

The relative risks of vertebral fractures of women receiving zoledronate-zoledronate and zoledronate-placebo infusions as compared with the placebo-placebo group were 0.56 (95% confidence interval [CI], 0.34 – 0.92; P=0.04) and 0.59 (95% confidence interval [CI], 0.36 – 0.97; P=0.08) respectively. The relative risks of any fracture in comparison with placebo-placebo group were 0.70 (95% confidence interval [CI], 0.56 – 0.88) in the zoledronate-zoledronate group and 0.77 (95% confidence interval [CI], 0.62 – 0.97) in the zoledronate-placebo group. Only few cases of episcleritis were noted in relation to baseline infusion of zoledronate.

To summarize, intravenous zoledronate administered once every 5 years reduced the incidence of morphometric vertebral fractures over a 10-year period in early postmenopausal women.

Source: www.nejm.org
 

FDA Approves Novel Non-Opioid Treatment for Moderate to Severe Acute Pain

Date: January 30, 2025

The U.S. Food and Drug Administration (FDA) has approved Journavx (suzetrigine), a first-in-class non-opioid analgesic, for the treatment of moderate to severe acute pain in adults. Journavx works by targeting sodium channels in the peripheral nervous system, interrupting pain signals before they reach the brain. This approval marks the introduction of a new therapeutic class for pain management, offering an alternative to opioids and their associated risks.

Acute pain, which often arises from injuries or surgeries, is commonly treated with analgesics, including opioids. Journavx provides a non-opioid option, aligning with the FDA’s Overdose Prevention Framework, which promotes the development of safer alternatives for pain management.

The efficacy of Journavx was demonstrated in two randomized, double-blind clinical trials involving patients recovering from abdominoplasty and bunionectomy. Participants were also allowed to use ibuprofen as needed for additional pain relief. Both trials demonstrated a statistically significant reduction in pain compared to placebo. The safety profile was reviewed in over 1,100 participants across trials, with common side effects including itching, muscle spasms, rash, and elevated creatine phosphokinase levels. Journavx should not be used with strong CYP3A inhibitors, and patients are advised to avoid grapefruit products while on the medication.

The FDA granted Journavx Breakthrough Therapy, Fast Track, and Priority Review designations to expedite its development and approval. Developed by Vertex Pharmaceuticals Incorporated, Journavx represents a significant step forward in reducing reliance on opioids for pain management and expanding treatment options.Source: www.fda.gov
 

Nivolumab-Ipilimumab Prolongs Progression-free Survival in Microsatellite Instability-high Metastatic Colorectal Cancer

Date: February 1, 2025

Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer patients are usually associated with poor outcomes in chemotherapy with or without targeted therapies. Various clinical practice guidelines have recommended the use of immune checkpoint inhibitors to improve progression-free survival in these patients. Both nivolumab and ipilimumab are possible immunotherapeutic options that target PD-1 and CTLA-4 pathway respectively for T cell reactivation.

In this randomized, open-label, international, phase 3 CheckMate 8HW trial, 839 patients with metastatic colorectal cancer), of which about 80% with centrally confirmed MSI-H or dMMR status, were randomly assigned in 2:2:1 ratio to receive nivolumab-ipilimumab (n=354), nivolumab monotherapy (n=353) or chemotherapy (n=132 in accordance with the research protocol for a maximum of 2 years. Dual primary endpoints of this study include progression-free survival for nivolumab-ipilimumab versus chemotherapy as first-line setting and nivolumab-ipilimumab versus nivolumab monotherapy across all lines of therapy.

The median progression-free survival was 54.1 months in the nivolumab-ipilimumab group and 5.9 months in the chemotherapy group (Hazard ratio=0.21, 95% confidence interval [CI], 0.14-0.31; P<0.001). Clinically significant improvement in progression-free survival was also noted in the nivolumab-ipilimumab group with a hazard ratio of 0.62 (95% confidence interval [CI], 0.48 – 0.81; P=0.0003), when compared with patients who underwent nivolumab monotherapy. The most common treatment-related adverse events were pruritis and diarrhoea throughout the study period, and the safety profiles were consistent with established profiles of each individual drug.

In conclusion, nivolumab-ipilimumab immunotherapy significantly prolongs progression-free survival across all treatment lines and appears as a potential new standard of care for the treatment of MSI-H or dMMR metastatic colorectal cancer.

Source: www.thelancet.com

 

Iptacopan Leads to Significant Improvement in Proteinuria among Patients with IgA Nephropathy

Date: February 6, 2025

IgA nephropathy (IgAN) refers to a form of glomerulonephritis caused by deposition of IgA antibody, which leads to progressive loss of kidney function. Presence of proteinuria in IgAN patients is now recognized as one of the risk factors for experiencing rapid renal function decline in particular. Iptacopan, an oral complement factor B inhibitor, inhibits the alternative pathway that potentially contributes to the pathogenesis of IgAN.

The phase 3, international, double-blind, randomized and placebo-controlled APPLAUSE-IgAN trial recruited eligible adults with biopsy-confirmed IgAN and proteinuria (defined as a 24-hour urinary protein-to-creatinine ratio ≥1) despite optimized supportive therapy. A total of 443 patients were then randomly assigned in 1:1 ratio to receive oral 200mg iptacopan (n=222) or placebo (n=221) twice daily for 24 months, alongside with the continuation of supportive treatment. The primary end point was the change from baseline in the 24-hour urinary protein-to-creatinine ratio at month 9. The safety profile of the newly developed iptacopan was also assessed in the current study.

Interim primary efficacy analysis showed that the adjusted geometric mean 24-hour urinary protein-to-creatinine ratio was 38.3% lower in the iptacopan group than placebo group (geometric mean ratio=0.617; 95% confidence interval [CI], 0.514 – 0.740; two-sided P<0.001) at month 9. Exploratory analyses regarding iptacopan’s effect on proteinuria also align with findings of complement pathway biomarkers returning to normal as of healthy individuals in the treatment group. The incidence of adverse events was similar in both groups, with no significant increase in infection risk being observed for patients treated with iptacopan.

In conclusion, oral iptacopan improves proteinuria as compared with placebo which may potentially benefit IgAN patients who are at risk of rapid deterioration of kidney function.        

Source: www.nejm.org

FDA Approves First Rapid-Acting Insulin Biosimilar Product for Diabetes Treatment

Date: February 14, 2025

The U.S. Food and Drug Administration (FDA) has approved Merilog (insulin-aspart-szjj), the first rapid-acting insulin biosimilar, as a treatment option for adults and children with diabetes mellitus. Merilog is biosimilar to Novolog (insulin aspart) and is designed to manage blood sugar levels around mealtimes, helping to reduce spikes in blood glucose. The FDA approval is granted to both a 3 mL prefilled pen and a 10 mL multiple-dose vial for subcutaneous injection.

This approval marks a significant milestone as Merilog becomes the third insulin biosimilar product approved by the FDA, following two long-acting biosimilars approved in 2021. Biosimilar products are highly similar to their reference products and offer no clinically meaningful differences in terms of safety, efficacy, or quality. By increasing competition in the insulin market, biosimilars like Merilog aim to expand patient access to these essential medications at potentially lower costs.

Diabetes affects over 38 million Americans, with approximately 8.4 million relying on insulin therapy, including rapid- and long-acting insulin. Insulin therapy is critical for managing blood sugar levels and preventing complications associated with diabetes. Merilog is administered subcutaneously by injection into the stomach, buttocks, thighs or upper arms, 5-10 minutes before a meal and should be dosed individually based on patient needs.

While Merilog offers a promising option for diabetes management, it carries risks of side effects such as hypoglycemia, severe allergic reactions, and hypokalemia. Common side effects include injection site reactions, itching, rash, and weight gain.

The FDA’s approval of Merilog, developed by Sanofi-Aventis U.S. LLC, underscores the agency's commitment to enhancing the availability of high-quality, affordable insulin products. This advancement holds the potential to make a meaningful difference for millions of patients managing diabetes daily.

Source: www.fda.gov
 

Oral Semaglutide Reduces Cardiovascular Risks in High-Risk Type 2 Diabetes Patients

Date: March 29, 2025

The cardiovascular safety of oral semaglutide, a GLP-1 receptor agonist, has been established in previous trials. However, the cardiovascular efficacy of oral semaglutide in patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or both has not been fully established.

In this international, double-blind, randomized, placebo-controlled, event-driven, superiority phase 3b trial, participants who were 50 years of age or older, had type 2 diabetes (HbA1c 6.5 to 10.0%), and had known ASCVD, CKD (defined by an eGFR <60 ml/min/1.73m²), or both were eligible. A total of 9,650 eligible participants were randomly assigned in a 1:1 ratio to receive either once-daily oral semaglutide (maximal dose, 14 mg) or placebo, in addition to standard care. The primary outcome was major adverse cardiovascular events (MACE), assessed in a time-to-first-event analysis. Secondary outcomes included major kidney disease events (a five-point composite outcome).

A primary outcome event occurred in 12% of participants (579 out of 4,825; 3.1 events per 100 person-years) in the oral semaglutide group, as compared with 13.8% (668 out of 4,825; 3.7 events per 100 person-years) in the placebo group (hazard ratio, 0.86; 95% confidence interval [CI], 0.77 to 0.96; P=0.006). The results for secondary outcomes did not differ significantly between the two groups.

Participants receiving semaglutide also experienced improvements in glycemic control and weight loss. The mean reduction in HbA1c was 0.71% compared to 0.15% in the placebo group (estimated difference, -0.56%; 95% CI, -0.61 to -0.52), and weight loss was 4.22 kg versus 1.27 kg with placebo (estimated difference, -2.95 kg; 95% CI, -3.18 to -2.73).

The safety profile of oral semaglutide was consistent with prior trials. Gastrointestinal side effects, including nausea and diarrhea, were slightly more common with semaglutide (5.0% vs. 4.4%). However, the incidence of serious adverse events was slightly lower in the semaglutide group (47.9% vs. 50.3%).

In conclusion, oral semaglutide demonstrates a significant reduction in cardiovascular risk for patients with type 2 diabetes and high cardiovascular risk, while also improving glycemic control and promoting weight loss.

Source: www.nejm.or