Archive for month: May, 2024

Researchers have found in phase 3 QWINT-2 and QWINT-4 trials that Once-weekly insulin efsitora alfa was as effective as daily basal insulin in adults with type 2 diabetes.

In the treat-to-target clinical trials, efsitora showed non-inferior A1C reduction compared to the most commonly used daily basal insulins globally.

“The results of QWINT-2 and QWINT-4 are a significant milestone for the diabetes community and demonstrate that efsitora as a weekly insulin provides blood sugar control equivalent to daily basal insulins,” said Jeff Emmick, MD, Ph.D., senior vice president, product development, Lilly. “With efsitora, we have an opportunity to provide an innovative once-weekly solution that safely achieves and maintains A1C control, reduces treatment burden of traditional daily injections and potentially improves adherence for people with diabetes.”

QWINT-2 evaluated the efficacy and safety of once-weekly efsitora compared to once-daily insulin degludec for 52 weeks. The trial randomized insulin-naïve adults with type 2 diabetes to receive efsitora once weekly or insulin degludec once daily and was also designed to assess efficacy in patients using and not using GLP-1 receptor agonists.

The trial met its primary endpoint of non-inferior A1C reduction with efsitora compared to insulin degludec at week 52. For the efficacy estimand, efsitora reduced A1C by 1.34% compared to 1.26% for insulin degludec resulting in an A1C of 6.87% and 6.95% respectively. In a key secondary endpoint, efsitora was non-inferior to insulin degludec in A1C change among participants using and not using GLP-1 receptor agonists. Further, participants taking efsitora spent 45 minutes more time in range and 37 minutes more in tight range without additional time in hypoglycemia (blood glucose <54 mg/dL) in comparison to insulin degludec.

QWINT-4 evaluated the efficacy and safety of efsitora compared to insulin glargine for 26 weeks in adults with type 2 diabetes who have previously been treated with basal insulin and at least two injections per day of mealtime insulin. The trial randomized participants to receive efsitora once weekly or insulin glargine once daily, both of which were administered with insulin lispro.

The trial met its primary endpoint of non-inferior A1C reduction with efsitora compared to insulin glargine at week 26. For the efficacy estimand, both efsitora and insulin glargine reduced A1C by 1.07% resulting in an A1C of 7.12% and 7.11%, respectively6,7.

In both QWINT-2 and QWINT-4, efsitora was safe and well-tolerated with estimated combined rates of severe or clinically significant (blood glucose <54 mg/dL) hypoglycemic events per patient-year of exposure of 0.58 with efsitora vs. 0.45 with insulin degludec (QWINT-2) and 6.6 with efsitora vs. 5.9 with insulin glargine (QWINT-4).

Detailed results from QWINT-2 will be presented at the European Association for the Study of Diabetes (EASD) Annual Meeting 2024. Topline readouts from QWINT-1, QWINT-3 and QWINT-5 are anticipated later this year.

About the QWINT clinical trial program

The QWINT phase 3 global clinical development program for insulin efsitora alfa (efsitora) in diabetes began in 2022 and has enrolled more than 4,000 people living with type 1 or type 2 diabetes across five global registration studies.

QWINT-2 (NCT05362058) was a parallel-design, open-label, treat-to-target, randomized controlled clinical trial comparing the efficacy and safety of efsitora as a once-weekly basal insulin to insulin degludec for 52 weeks in insulin-naïve adults with type 2 diabetes. The trial randomized 928 participants across the U.S., Brazil, Canada, China, Czechia (Czech Republic), Germany, Greece, Japan, Korea, Mexico and Puerto Rico to receive efsitora once weekly or insulin degludec once daily administered subcutaneously. The primary objective of the trial was to demonstrate non-inferiority in reducing A1C at week 52 with efsitora compared to insulin degludec. The trial was also designed to assess efficacy and safety for patients using and not using GLP-1 receptor agonists.

QWINT-4 (NCT05462756) was a parallel-design, open-label, treat-to-target, randomized controlled clinical trial comparing the efficacy and safety of efsitora as a weekly basal insulin to insulin glargine for 26 weeks in adults with type 2 diabetes who have previously been treated with basal insulin and at least two injections per day of mealtime insulin. The trial randomized 730 participants across the U.S., Argentina, Germany, India, Italy, Mexico, Puerto Rico and Spain to receive efsitora once weekly or insulin glargine once daily, both of which were administered subcutaneously along with insulin lispro. The primary objective of the trial was to demonstrate non-inferiority in reducing A1C at week 26 with efsitora compared to insulin glargine.

About insulin efsitora alfa

Insulin efsitora alfa (efsitora) is a once-weekly basal insulin, a fusion protein that combines a novel single-chain variant of insulin with a human IgG2 Fc domain. It is specifically designed for once-weekly subcutaneous administration, and with its low peak-to-trough ratio, it has the potential to provide more stable glucose levels (less glucose variability) throughout the week. Efsitora is in phase 3 development for adults with type 1 and 2 diabetes.

Recently published research paper focuses on the management of gynecomastia in males, particularly the case of a 24-year-old male with long-standing left breast gynecomastia who underwent surgery. The paper discusses the pathophysiology of gynecomastia, its prevalence, and treatment, emphasizing that surgical resection of the breast tissue is a common approach.

Novel Anesthetic Methods for Breast Procedures

The paper also presents the utilization of thoracic segmental spinal anesthesia and erector spinae plane block as alternative anesthetic methods for breast procedures, highlighting their benefits such as regulation of the neuroendocrine stress response, lower need for analgesics post-surgery, and decreased postoperative nausea and vomiting. The authors suggest that these methods offer a compelling substitute for general anesthesia, with potential for expanded application in varied surgical scenarios through additional research and clinical experience.

Successful Application of Novel Anesthetic Techniques

The case presentation details the successful application of these novel anesthetic techniques in the 24-year-old male patient with left breast enlargement. The patient underwent thoracic segmental spinal anesthesia and erector spinae plane block, with stable vital signs and minimal intraoperative anesthetic requirements. Postoperatively, the patient experienced minimal pain and a speedy recovery.

Beneficial Anesthetic Strategy for Breast Procedures

The authors recommend the combination of erector spinae block with thoracic segmental spinal anesthesia as a feasible and beneficial anesthetic strategy for breast procedures, asserting its advantages over general anesthesia. They highlight the methods’ potential for improved intra-operative hemodynamic stability, increased patient compliance, and efficient postoperative pain control, particularly for patients undergoing breast surgery.

Overall, the paper underscores the efficacy and safety of these anesthetic techniques, positioning them as valuable alternatives to conventional general anesthesia in breast procedures, and advocates for further research and clinical practice to explore their potential benefits in a broader range of surgical scenarios.

Reference –

Paul A, Borkar A (October 23, 2023) Anaesthetic Management for Mastectomy in a Male With Unilateral Gynecomastia: The Utilization of Thoracic Segmental Spinal Anaesthesia and Erector Spinae Plane Block. Cureus 15(10): e47502. doi:10.7759/cureus.47502.

Vanda Pharmaceuticals Inc. announced strong results from its second Phase III study of tradipitant for motion sickness which confirms the previous findings of the drug’s efficacy in preventing vomiting associated with the condition. This pivotal study was conducted in real-world conditions aboard boats in the coastal waters of the US which added significant credibility to the results.

The multicenter, randomized, double-blind, placebo-controlled trial involved 316 participants. These participants had a history of motion sickness and embarked on 20 boat trips under various sea conditions between September 2023 and April 2024. The study evaluated the effectiveness of two doses of tradipitant, 170 mg and 85 mg against a placebo. The primary endpoint of the study was the prevention of vomiting with the 170 mg dose of tradipitant. Secondary endpoints included the effectiveness of the 85 mg dose and the prevention of severe nausea and vomiting for both doses.

The results were highly favorable for tradipitant where only 10.4% of participants on the 170 mg dose and 18.3% on the 85 mg dose underwent vomiting when compared to 37.7% in the placebo group. These findings represent a significant reduction in the risk of vomiting which was over 70% for the 170 mg dose and over 50% for the 85 mg dose (p=0.000002 and p=0.0014, respectively).

Tradipitant also demonstrated significant efficacy in preventing severe nausea and vomiting. When data from both doses were combined, only 13.3% of the participants reported severe symptoms versus 33.0% in the placebo group (p=0.00003). Motion sickness is a common issue with limited effective treatments. The U.S. Food and Drug Administration (FDA) has not approved a new medication for motion sickness in over 40 years, the last being scopolamine in 1979. Existing treatments often suffer from low efficacy or significant side effects. 

Vanda Pharmaceuticals plans to submit a New Drug Application (NDA) for tradipitant to the FDA in the fourth quarter of 2024 by hoping to address this longstanding unmet need. The Motion Serifos study provided strong evidence for the efficacy of tradipitant in preventing vomiting and severe nausea associated with motion sickness. The participants who took the higher 170 mg dose of tradipitant had a notable lower incidence of vomiting when compared to the individuals on a placebo with a risk reduction of over 70%. Also, the 85 mg dose also showed a significant reduction in vomiting incidence by over 50% when compared to placebo. In conclusion, the combined analysis of both doses showed a substantial reduction in severe nausea and vomiting which indicates the potential of tradipitant as a comprehensive treatment for motion sickness symptoms.

Source:

Vanda Pharmaceuticals Inc. (2024, May 15). Vanda pharmaceuticals reports positive results from a second Phase III study of tradipitant in motion sickness. PR Newswire. https://www.prnewswire.com/news-releases/vanda-pharmaceuticals-reports-positive-results-from-a-second-phase-iii-study-of-tradipitant-in-motion-sickness-302146315.html

Autoimmune diseases occur when the body’s immune system attacks healthy cells instead of protecting them. Systemic sclerosis (SSc) is one such autoimmune condition characterized by faulty circulatory and immune systems, leading to the occurrence of fibrosis (hardening and scarring of healthy tissue) of the skin and internal organs. SSc is known to affect patients throughout their lives, thereby, impairing their quality of life. Although precise mechanisms underlying SSc development and progression are not clearly understood, a complex interplay of immune, hormonal, environmental, and genetic factors is often implicated.

Moreover, around 90% of the patients with SSc are known to experience a phenomenon known as the ‘Raynaud’s phenomenon (RP).’ It is associated with spasms in smaller blood vessels, leading to decreased blood flow. RP can, in turn, promote an increase in the generation of molecules called reactive oxygen species (ROS). The resulting oxidative environment triggers cell damage and fibrosis, further exacerbating the disease. Countering oxidative stress using antioxidant compounds, is therefore, being increasingly explored as a therapeutic strategy. However, a single antioxidant may not be therapeutically effective in decreasing oxidative stress.

To this end, a team of researchers from Japan, led by Professor Haruhiko Inufusa, who is the Chief Research Scientist at the Louis Pasteur Center for Medical Research, and a distinguished faculty at the Division of Anti-Oxidant Research, Life Science Research Center, Gifu University, has investigated the effectiveness of Twendee X® (TwX)-a dietary supplement comprising of a combination of eight active antioxidants-in reducing oxidative stress in SSc mouse models.

Explaining the rationale behind their work published, in the International Journal of Molecular Sciences, Prof. Inufusa says, “Studies have shown that TwX reduces ROS, protects mitochondrial function, and improves cognition and memory. Daily oxidative stress care with this supplement can contribute not only to daily health maintenance and disease prevention but also to the symptomatic improvement of intractable diseases like SSc.”

The eight constituents of TwX include vitamin C, L-glutamine, niacin, L-cystine, coenzyme Q10, vitamin B2, succinic acid, and fumaric acid. The combined antioxidant effect is likely more potent than the activity of either compound alone. Previous studies have demonstrated improvement in cognition, memory, and motor coordination in mouse models of dementia, and reduction in affected region size, oxidative stress, and inflammation in mouse models of ischemic stroke following treatment with TwX. Based on these findings, the researchers conducted this study to investigate the effects of TwX in a mouse model of SSc created using hypochlorous acid (HOCl).

HOCl induction led to a significant increase in the serum levels of advanced oxidation protein products (AOPP), mimicking SSc-like features. Further HOCl induction led to the thickening of skin tissues along with local and systemic inflammation, fibrosis, and vascular injury.

Notably, the AOPP levels of mice treated with TwX were substantially lower than that of the healthy animals. Moreover, TwX treatment significantly reduced skin thickness, accumulation of the collagen protein, skin levels of hydroxyproline-an oxidative stress marker, and fibrosis of the skin and lungs. Additionally, TwX treatment significantly reduced the levels of α-smooth muscle actin (α-SMA), a protein that was elevated in response to HOCl induction and has been shown to activate ROS in fibrotic diseases. HOCl-induced animals treated with TwX also demonstrated a decreasing trend in the levels of inflammatory cytokines and activated immune cells involved in inflammatory responses.

Overall, these results suggest that TwX may treat SSc by regulating oxidative stress, and reducing skin and lung fibrosis. Since these findings were observed in a mouse model, further studies will be needed to establish the effectiveness of TwX in human patients with SSc. Nevertheless, given the benefits of TwX in other oxidative stress-related diseases as well as the lack of side-effects, TwX holds significant promise as an antioxidant therapeutic against SSc.

Sharing his concluding thoughts about their study, Prof. Inufusa says, “Although TwX is a dietary supplement, it has passed drug-level safety testing and can be used by a wide range of people, from children to adults. Moreover, our findings suggest that TwX could potentially alleviate the symptoms of intractable oxidative stress-related diseases such as SSc.”

Reference:

You F, Nicco C, Harakawa Y, Yoshikawa T, Inufusa H. The Potential of Twendee X® as a Safe Antioxidant Treatment for Systemic Sclerosis. International Journal of Molecular Sciences. 2024; 25(5):3064. https://doi.org/10.3390/ijms25053064.

Poland: Heart transplantation stands as a life-saving intervention for individuals with end-stage heart failure. Yet, even after a successful transplant, recipients face ongoing challenges, including the risk of cardiac allograft vasculopathy (CAV), a form of coronary artery disease unique to transplant patients. In this context, the utility of advanced imaging techniques like 64-slice coronary computed tomography angiography (CCTA) is gaining significant attention for its potential to revolutionize post-transplant care.