Richard Keen, MD, PhD, Director of the Metabolic Bone Disease Centre at the Royal National Orthopaedic Hospital in London and global principal investigator of the OPTIMA trial, discusses positive 84-week results from the phase 3 OPTIMA trial extension, evaluating Pasatru (garetosmab-grts) in adults with fibrodysplasia ossificans progressiva (FOP).

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Bradley Dixon, MD, a pediatric nephrologist, and Chief of Pediatric Nephrology, Children’s Hospital of Colorado, and Professor of Pediatrics, University of Colorado School of Medicine, discussed complement 3 glomerulopathy (C3G) with CheckRare.

Complement 3 glomerulopathy (or C3G) is a form of membranoproliferative glomerulonephritis, an inflammatory process. It occurs when the complement system, which is a key part of the body’s defenses to fight off bacterial and viral infection, is continually engaged. When this occurs, plasma complement fragments are deposited in the glomerulus, creating inflammation and disrupting glomerular function. At this point, the clinical features of C3G are apparent, including hematuria and proteinuria.

As it is a rare disorder, it is not regularly taught during medical training, and primary care physicians will not typically see several patients with C3G. Therefore, it will not often be in the forefront of clinician’s mind when confronted with symptoms associated with C3G. Primarily a disease of the young, pediatricians may easily mistake it for other conditions, such as postinfectious (or infection-related) glomerulonephritis, which typically follows a streptococcal infection. The microscopic appearance of biopsy samples from patients with C3G may even look similar to those with postinfectious glomerulonephritis.

The VALIANT trial was a phase 3, double-blind, placebo-controlled study of the efficacy and safety of pegcetacoplan in 124 adolescent and adult patients with either C3G or the related disorder primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN). The primary endpoint was to determine this complement 3 inhibitor’s effect on proteinuria.

After 26 weeks of treatment, pegcetacoplan was associated with a 68% relative reduction in the urinary protein:creatinine ratio, the indicator of proteinuria, compared with the individuals receiving placebo. The study drug was not associated with a safety profile that was significantly different from that observed in the placebo group. A longer-term extension study demonstrated that the proteinuria reduction is maintained, along with kidney function, through at least 52 weeks. “Improvement in proteinuria really does herald long-term benefit,” stated Dr. Dixon. “The longer we see preservation of GFR, the more confident we are that these drugs will be effective over the long term.”

The VALIANT data support that blocking C3 has dramatic benefits by limiting complement deposition in the glomerulus in both adolescent and adults with C3G. With earlier intervention, long-term damage to kidney function may be prevented.

Dr. Dixon commented that although pegcetacoplan was effective in patients ages 12 years or greater, there is still an urgent need for treatment of younger patients, for which no effective treatment is approved. He added that since we are all born with a fixed number of glomeruli, kidney damage in young patients means their reserve of kidney function later in life will be limited. In his experience, 50% of patients with C3G will experience a halving of their kidney function within 10 years, and will need dialysis and/or a kidney transplant.

Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community.

Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com.

Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community.

Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

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Maria Picone, co-founder and CEO of the TREND Community, and mother of a 14-year-old with Prader-Willi syndrome (PWS), discusses her family’s journey with PWS, including why more research and better data are so important.

Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community.

Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com.

Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community.

Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

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Bradley Dixon, MD, a pediatric nephrologist, and Chief of Pediatric Nephrology, Children’s Hospital of Colorado, and Professor of Pediatrics, University of Colorado School of Medicine, discussed complement 3 glomerulopathy (C3G) with CheckRare.

Complement 3 glomerulopathy (or C3G) is a form of membranoproliferative glomerulonephritis, an inflammatory process. It occurs when the complement system, which is a key part of the body’s defenses to fight off bacterial and viral infection, is continually engaged. When this occurs, plasma complement fragments are deposited in the glomerulus, creating inflammation and disrupting glomerular function. At this point, the clinical features of C3G are apparent, including hematuria and proteinuria.

As it is a rare disorder, it is not regularly taught during medical training, and primary care physicians will not typically see several patients with C3G. Therefore, it will not often be in the forefront of clinician’s mind when confronted with symptoms associated with C3G. Primarily a disease of the young, pediatricians may easily mistake it for other conditions, such as postinfectious (or infection-related) glomerulonephritis, which typically follows a streptococcal infection. The microscopic appearance of biopsy samples from patients with C3G may even look similar to those with postinfectious glomerulonephritis.

The VALIANT trial was a phase 3, double-blind, placebo-controlled study of the efficacy and safety of pegcetacoplan in 124 adolescent and adult patients with either C3G or the related disorder primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN). The primary endpoint was to determine this complement 3 inhibitor’s effect on proteinuria.

After 26 weeks of treatment, pegcetacoplan was associated with a 68% relative reduction in the urinary protein:creatinine ratio, the indicator of proteinuria, compared with the individuals receiving placebo. The study drug was not associated with a safety profile that was significantly different from that observed in the placebo group. A longer-term extension study demonstrated that the proteinuria reduction is maintained, along with kidney function, through at least 52 weeks. “Improvement in proteinuria really does herald long-term benefit,” stated Dr. Dixon. “The longer we see preservation of GFR, the more confident we are that these drugs will be effective over the long term.”

The VALIANT data support that blocking C3 has dramatic benefits by limiting complement deposition in the glomerulus in both adolescent and adults with C3G. With earlier intervention, long-term damage to kidney function may be prevented.

Dr. Dixon commented that although pegcetacoplan was effective in patients ages 12 years or greater, there is still an urgent need for treatment of younger patients, for which no effective treatment is approved. He added that since we are all born with a fixed number of glomeruli, kidney damage in young patients means their reserve of kidney function later in life will be limited. In his experience, 50% of patients with C3G will experience a halving of their kidney function within 10 years, and will need dialysis and/or a kidney transplant.

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Bradley Dixon, MD, a pediatric nephrologist, and Chief of Pediatric Nephrology, Children’s Hospital of Colorado, and Professor of Pediatrics, University of Colorado School of Medicine, discusses complement 3 glomerulopathy (C3G) and its diagnostic challenges.

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Bradley Dixon, MD, a pediatric nephrologist, and Chief of Pediatric Nephrology, Children’s Hospital of Colorado, and Professor of Pediatrics, University of Colorado School of Medicine, discusses the impact of Empaveli on proteinuria and kidney function in C3G.

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Bradley Dixon, MD, a pediatric nephrologist, and Chief of Pediatric Nephrology, Children’s Hospital of Colorado, and Professor of Pediatrics, University of Colorado School of Medicine, discusses the long-term impact of Empaveli on patients with C3G.

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Bradley Dixon, MD, a pediatric nephrologist, and Chief of Pediatric Nephrology, Children’s Hospital of Colorado, and Professor of Pediatrics, University of Colorado School of Medicine, discusses treatment gaps in C3G.

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Bradley Dixon, MD, a pediatric nephrologist, and Chief of Pediatric Nephrology, Children’s Hospital of Colorado, and Professor of Pediatrics, University of Colorado School of Medicine, discusses the urgency of diagnosis and treatment in C3G.

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