Pegcetacoplan Maintains Kidney Benefits at 52 Weeks
The 26-week results, which were presented last October at Kidney Week 2024, showed a highly significant difference in change in proteinuria from baseline, as measured by the urine protein-to-creatinine ratio (uPCR); the reduction was 67.2% with pegcetacoplan vs 2.9% with placebo ( P < .0001).
The current findings showed that not only were these benefits sustained in patients who remained on pegcetacoplan, patients who switched from placebo to pegcetacoplan also experienced reductions of similar magnitude, said Fadi Fakhouri, MD, of Lausanne University Hospital and the University of Lausanne, Switzerland.
Fakhouri presented the 1-year results at the 62nd European Renal Association (ERA) Congress 2025.
VALIANT Open-Label Period
The phase 3 VALIANT trial involved 124 patients with native or post-transplant
recurrent C3 glomerulopathy or primary IC-MPGN who were randomly assigned to treatment two times a week with either subcutaneous pegcetacoplan 1080 mg, or weight-based doses for adolescents weighing ≤50 kg (n = 63); or to placebo (n = 61). In the subsequent 26-week open-label period, the placebo group crossed over and all patients received pegcetacoplan.
Overall, 59 (93.7%) people in the pegcetacoplan group and 55 (90.2%) in the placebo group completed the study treatment and 52-week assessment.
At week 52, patients in the original pegcetacoplan group maintained the significant proteinuria reduction that was observed at week 26, with a mean urine protein-to-creatinine ratio (UPCR) change at week 26 of –67.2% and at week 52 of –68.3%.
Patients in the placebo group, who experienced a +3.2% change in uPCR at week 26, experienced a reduction of –51.3% at week 52 after being switched to pegcetacoplan.
In addition, eGFR levels in the pegcetacoplan group dropped slightly from -1.2 mL/min/1.73 m2 at week 26 to -3.7 mL/min/1.73 m2 at week 52; in the placebo-to-pegcetacoplan group, the corresponding changes were -7.9 mL/min/1.73 m2 at week 26 and -4.7 mL/min/1.73 m2 at week 52.
In terms of safety, pegcetacoplan remained well-tolerated in the second 26 weeks, and treatment-emergent adverse events (TEAEs) were similar between the two arms during the open-label period (pegcetacoplan-to-pegcetacoplan, 77%; placebo-to-pegcetacoplan, 73.7%).
Overall, infusion-related TEAEs decreased from the randomized to open-label period in the pegcetacoplan-to-pegcetacoplan group (33.3% vs 9.8%, respectively), suggesting an improvement in tolerability over time.
Adherence was high, at 97.6% of patients having an adherence of ≥90% to ≤100%, overall.
Infections included two cases of pneumococcal pneumonia (including one that was serious) occurring during the open-label period, and there was one case each of streptococcal pharyngitis and urinary tract infection caused by Escherichia .
No patient deaths or allograft losses were reported.
'The open-label period results confirm pegcetacoplan's significant effect on kidney function,' Fakhouri said.
'Patients in the placebo arm experienced a decline in eGFR during the randomized controlled period, but a stabilization after switching to pegcetacoplan, comparable to randomized controlled period results in the pegcetacoplan group,' he added.
Patients With Baseline Nephrotic Range Proteinuria
The results of subanalyses looking at several other trial outcomes were also presented at the meeting.
These included an analysis of patients with nephrotic range proteinuria at baseline, who are at a notably high risk of rapid disease progression to kidney failure.
At baseline, 24 patients in the pegcetacoplan arm (38.1%) and 16 in the placebo arm (26.2%) had nephrotic range proteinuria, defined as a uPCR ratio ≥3 g/g.
At the end of the initial 26-week period, among patients with nephrotic range proteinuria, those treated with pegcetacoplan had a relative reduction of proteinuria of 72.1% compared with placebo ( P < .0001).
Patients Treated With Immunosuppressive Therapies
A second subanalysis evaluated outcomes among 48 (76%) participants in the pegcetacoplan group and 42 (69%) in the placebo group who were receiving concomitant immunosuppressive therapy at baseline.
Patients were permitted to continue the immunosuppressants provided that the doses had remained stable during the preceding 12-week period and throughout the trial.
The outcomes between the two groups were similar: Immunosuppressant-treated patients who received pegcetacoplan had a relative reduction of 70% in proteinuria vs placebo ( P < .0001), and among patients who did not receive immunosuppressants, the relative reduction was 64.5% compared to placebo ( P = .0005).
At week 26, 62.5% (30/48) of immunosuppressant‐treated patients receiving pegcetacoplan achieved a ≥50% reduction in proteinuria from baseline vs 4.8% (2/42) on placebo ( P < .0001). Among those not on immunosuppressants, 53.3% (8/15) of the pegcetacoplan group met the same endpoint compared with 5.3% (1/19) in the placebo arm ( P = .0087).
'Reassuringly, proteinuria was reduced in both groups, and the immunosuppressed group had a highly statistically significant reduction,' said David Kavanagh, MD, of the National Renal Complement Therapeutics Centre, Newcastle University, Newcastle upon Tyne, United Kingdom, who presented this subanalysis.
Other outcomes, including stabilization of eGFR, were also similar to the overall reductions, including those patients not on immunosuppressants.
Importantly, rates of TEAEs were also comparable between the immunosuppressed and non-immunosuppressed patients.
'If you can reduce your proteinuria by at least 50%, you're going to have an outcome that can reduce the risk of kidney failure,' Kavanagh concluded.
The studies were sponsored by Apellis. Fakhouri reported relationships with Apellis, Sobi, Novartis, Roche, Alexion Pharmaceuticals, and AstraZeneca. Kavanagh reported relationships with Idorsia, Novartis, Chemocentryx, Alexion Pharmaceuticals, Samsung, Sobi, Gyroscope Therapeutics, Purespring, and Apellis.
Hashtags
Try Our AI Features
Explore what Daily8 AI can do for you:
Comments
No comments yet...
Related Articles
Yahoo
an hour ago
- Yahoo
The disease which takes 3.5 years to diagnose after symptoms start
A disease that affects almost one million people in the UK takes around 3.5 years to diagnose, researchers have found. Dementia sufferers have to wait a lengthy time from the onset of symptoms to an official diagnosis. And some people with early-onset dementia have an even longer wait of just over four years. A new study by UCL researchers is the first systematic review and meta-analysis of global evidence examining time to diagnosis in dementia. READ MORE: Learner drivers 'struggling to pass' as three Midland test centres among the UK's toughest The researchers reviewed data from 13 previously published studies which took place in Europe, US, Australia and China, reporting data on 30,257 participants. The study, published in the International Journal of Geriatric Psychiatry, investigated the average interval between symptom onset rated by patients or family carers using interviews or medical records to the final diagnosis of dementia. Lead author, Dr Vasiliki Orgeta, said: "Timely diagnosis of dementia remains a major global challenge, shaped by a complex set of factors, and specific healthcare strategies are urgently needed to improve it. "Other studies estimate that only 50-65% of cases are ever diagnosed in high-income countries, with many countries having even lower diagnostic rates. 'Timely diagnosis can improve access to treatments and for some people prolong the time living with mild dementia before symptoms worsen.' In a pooled meta-analysis of 10 of the included studies, the researchers found that it typically takes 3.5 years from the first alert of symptoms to a patient receiving a diagnosis of dementia, or 4.1 years for those with early-onset dementia, with some groups more likely to experience longer delays, a spokesperson for UCL said. They found that younger age at onset and having frontotemporal dementia were both linked to longer time to diagnosis. While data on racial disparities was limited, one of the studies reviewed found that black patients tended to experience a longer delay before diagnosis. Dr Orgeta said: 'Our work highlights the need for a clear conceptual framework on time to diagnosis in dementia, developed in collaboration with people with dementia, their carers, and supporters.' Dr Phuong Leung (UCL Division of Psychiatry) said: 'Symptoms of dementia are often mistaken for normal ageing, while fear, stigma, and low public awareness can discourage people from seeking help.' Professor Rafael Del-Pino-Casado, of the University of Jaén, Spain, said: 'Within healthcare systems, inconsistent referral pathways, limited access to specialists, and under-resourced memory clinics can create further delays. For some, language differences or a lack of culturally appropriate assessment tools can make access to timely diagnosis even harder.' Dr Orgeta added: 'To speed up dementia diagnosis, we need action on multiple fronts. Public awareness campaigns can help improve understanding of early symptoms and reduce stigma, encouraging people to seek help sooner. "Clinician training is critical to improve early recognition and referral, along with access to early intervention and individualised support so that people with dementia and their families can get the help they need.' The NHS lists common early symptoms of dementia as: memory loss difficulty concentrating finding it hard to carry out familiar daily tasks, such as getting confused over the correct change when shopping struggling to follow a conversation or find the right word being confused about time and place mood changes
Yahoo
2 hours ago
- Yahoo
Zamalek Appoints Villarreal Doctor Gerard Manzanet to Lead Medical Staff
Spanish sports medicine expert to head Zamalek's medical team as part of international revamp Zamalek Appoints Villarreal Doctor Gerard Manzanet to Lead Medical Staff Zamalek SC've officially named Spanish doctor Gerard Manzanet as the new head of the club's medical department, the board announced on Sunday. Advertisement The decision was made by sporting director John Edward in coordination with the club board, led by Hussein Labib as part of broader strategy to boost the team's medical structure with world class expertise. Top Level La Liga Experience Dr. Manzanet's renowned name in Spanish football having served as first team doctor at Villarreal CF since November 2021 and brings with him extensive experience from La Liga. He holds a Master's degree in Sports Medicine from TECH University, a FIFA /CIES diploma in football medicine and specialized credentials in sports emergency care, orthopedic injuries and musculoskeletal MRI from Francisco de Vitoria University in Spain. He's also WADA certified.
Yahoo
4 hours ago
- Yahoo
What makes the Mediterranean diet so healthy?
The Mediterranean diet has long been considered one of the healthiest dietary options for a long life. But, why is that the case? Researchers say the answer lies both in the nutritious value of the meals and in their anti-inflammatory ingredients, such as dark leafy greens and olive oil. 'The Mediterranean diet is probably one tool to keep your underlying systems in harmony with each other, and that may make you less vulnerable,' Dr. Annie Moore, a University of Colorado School of Medicine internal medicine specialist, said in a statement. Eating anti-inflammatory foods — including nuts, tomatoes, and salmon — is important to help reduce inflammation. Inflammation, which is our immune system's natural response to invaders, can be harmful when it persists. Chronic inflammation has been linked to heart disease, respiratory illness, autoimmune disease, arthritis, dementia, cancer, and other conditions, according to the Cleveland Clinic. Other foods have been tied to chronic inflammation, including those with high-fat and sugar content. "Many experimental studies have shown that components of foods or beverages may have anti-inflammatory effects," Dr. Frank Hu, a professor of nutrition and epidemiology at the Harvard School of Public Health, said. So, the next time you make a meal, what do you choose to stay Mediterranean diet-compliant? If you're choosing a protein, make it fishy. Oily fish including salmon, mackerel, and sardines are rich in omega-3 fats, which have been shown to exhibit anti-inflammatory properties. Maybe also reach for fish oil, but know that there's no convincing evidence to recommend them, according to Harvard Women's Health Watch. 'Fish oil contains omega-3 fatty acids, which are part of a healthy diet that is associated with lower levels of inflammation. Your body can't manufacture omega-3 fatty acids —eicosapentaenoic acid, docosahexaenoic acid, and alpha-linolenic acid — so it's important to get them through your diet,' Harvard Health said. Experts say to cook that fish in extra-virgin olive oil, which contains anti-oxidants that fight inflammation. One is known as oleocanthal, which 'has been shown to work like ibuprofen,' according to Harvard Health. Olive oil can help fight arthritis symptoms throughout the body, according to the Arthritis Foundation. 'Antioxidants are almost like a shield around your cells, like a blanket around them to protect them from oxidative damage,' registered dietitian Julia Zumpano explained to the Cleveland Clinic. But, it's not just olive oil that's a great source of antioxidants. As a side, reach for the greens and the beans, David Dunaief, an internist in New York, told The Washington Post. 'Dark, leafy green vegetables may lower inflammation by increasing antioxidant levels,' he said. There are many versions of a Mediterranean diet. The MIND diet, or 'Mediterranean-DASH Intervention for Neurodegenerative Delay' diet, targets the health of the aging brain with its selection. Whereas the DASH diet, or 'Dietary Approaches to Stop Hypertension' eating plan, is focused on fighting high blood pressure. Make sure to avoid ultraprocessed foods, including soda, smoked meat, chips, white bread, and others that are high in saturated fats, sodium, and sugar. Recent research has tied eating ultraprocessed food to an increased risk of lung cancer. Instead, grab a whole wheat roll, put nuts and tomatoes in a salad, and eat blueberries and other fruit for — or, at least, with — your dessert. Cherries are in season! 'Sometimes it's easier to add healthy foods than taking other foods away,' Moore said.
