Piasky (crovalimab)
Research Synopsis
- - Piasky (crovalimab) is a monoclonal antibody targeting complement component C5, recently approved for treating paroxysmal nocturnal hemoglobinuria (PNH) among other complement-mediated diseases.
- - Crovalimab offers an advantageous subcutaneous administration option once every four weeks, in contrast to existing treatments which often involve more frequent intravenous infusions.
- - Clinical trials, including the phase 1/2 COMPOSER study and the COMMODORE 3 study, have demonstrated crovalimab's effectiveness in controlling hemolysis in PNH patients, with approximately 78.7% achieving treatment success without serious side effects.
- - The medication has shown high tolerability in long-term studies, with side effects reported in only 32% of patients during the extension phases, confirming its durable efficacy over three years of treatment.
- - Research is ongoing to better understand drug-target-drug complexes (DTDCs) formed when switching between C5 inhibitors, aiming to optimize laea levels and enhance patient outcomes.
- - The drug has also been highlighted for its promising role amidst the emergence of patient needs in managing breakthrough hemolysis (BTH), a common challenge faced with existing therapies.
- - Crovalimab's approval represents a significant advancement in the treatment landscape for PNH, specifically for patients previously naive to complement inhibitors, and it is currently under review in various countries like the USA and EU after being launched in China and Japan.
- - The latest findings emphasize the need for tailored treatment strategies in managing PNH, suggesting that crovalimab may improve patient adherence and overall life quality through simplified dosing schedules.
- - Emerging studies continue to explore the implications of complement inhibition for various diseases beyond PNH, showcasing the broader therapeutic potential of crovalimab and similar agents in clinical practice.
- - Future research may focus on further refining treatment protocols and addressing limitations such as extravascular hemolysis and the optimization of transition strategies between different complement inhibitors.
Piasky (crovalimab)
The complement C5 inhibitor crovalimab in paroxysmal nocturnal hemoglobinuria.
London, UK
2 hours ago
1 Received
- Complement C5 inhibition is essential for treating paroxysmal nocturnal hemoglobinuria (PNH) due to its severe symptoms, but current treatments are mostly IV-only, posing challenges for drug development.
- Crovalimab, a new monoclonal antibody designed for self-administered subcutaneous dosing, was tested in a clinical trial to evaluate its safety and effectiveness in PNH patients who hadn't received complement inhibitors or were switching from them.
- The trial showed that crovalimab achieved effective inhibition of the terminal complement pathway with good safety outcomes, leading to the conclusion that it should proceed to further clinical development.
$100 - $150
Hourly Rate
An interview with Nancy Valente, the Global Head of Hematology Development at Roche.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
[Antibody therapy for paroxysmal nocturnal hemoglobinuria].
London, UK
2 hours ago
1 Received
- Eculizumab (Soliris) significantly enhances the quality of life for patients with paroxysmal nocturnal hemoglobinuria (PNH) by reducing hemolysis, alleviating related symptoms, and preventing thrombosis, but requires biweekly infusions, posing convenience challenges.
- An improved version, ravulizumab (Ultomiris), allows for infusions every 8 weeks, and a new drug, crovalimab (SKY59), is being developed for subcutaneous administration every 4 weeks, enhancing patient convenience.
- Ongoing research is focused on developing newer anti-complement drugs, aiming to balance efficacy, safety, and convenience in PNH treatment to better serve patients' needs.
$100 - $150
Hourly Rate
[Current treatment of paroxysmal nocturnal hemoglobinuria and prospects for new therapeutic agents in the future].
London, UK
2 hours ago
1 Received
- * Eculizumab, an anti-C5 monoclonal antibody, has shown significant benefits by reducing hemolysis and improving quality of life for PNH patients, along with newer antibodies that enhance treatment convenience.
- * Current clinical trials are exploring other complement inhibitors to address the issue of anemia from extravascular hemolysis and aim to improve efficacy, safety, and convenience in PNH treatments.
$100 - $150
Hourly Rate
[Novel therapeutics for paroxysmal nocturnal hemoglobinuria].
London, UK
2 hours ago
1 Received
- Recent findings on mutations in PIGT and PIGB genes have redefined paroxysmal nocturnal hemoglobinuria (PNH) as a hematopoietic stem cell disease characterized by complement-mediated hemolysis.
- Eculizumab (Soliris) treatment has significantly improved patients' quality of life by reducing hemolysis, alleviating symptoms, and preventing thrombosis.
- Although new antibody recycling techniques have improved treatment convenience, issues of extravascular hemolysis have emerged, prompting efforts to find more effective and convenient therapeutic options focusing on proximal complement inhibitors.
$100 - $150
Hourly Rate
Paroxysmal nocturnal hemoglobinuria: advances in the understanding of pathophysiology, diagnosis, and treatment.
London, UK
2 hours ago
1 Received
- Recent advancements in the understanding of paroxysmal nocturnal hemoglobinuria (PNH) have improved diagnostics and therapies, focusing on the unique survival of PNH stem cells against cell death.
- Changes in immune-related proteins (cytokines and chemokines) among PNH patients suggest a link to autoimmune processes and cell death mechanisms.
- The review discusses current diagnostic methods, treatment options (like C5 inhibitors and stem cell transplantation), and introduces new experimental drugs, emphasizing the significance of tailored treatment plans for better disease outcomes.
$100 - $150
Hourly Rate
Complement System as a New Target for Hematopoietic Stem Cell Transplantation-Related Thrombotic Microangiopathy.
London, UK
2 hours ago
1 Received
- Thrombotic microangiopathy (TMA) can occur after stem cell transplants, known as transplant-associated thrombotic microangiopathy (TA-TMA), but its causes and effective diagnosis are still unclear, leading to a high risk of mortality.
- Key symptoms of TA-TMA include low platelet levels, hemolysis, and organ damage, especially to the kidneys, which can also cause high blood pressure, but diagnosing it is complicated by other potential health issues.
- Recent research indicates that the complement system plays a role in TA-TMA, suggesting that complement inhibition therapy might help some patients, particularly if they show clear signs of complement activation; two medications, eculizumab and narsoplimab, have
$100 - $150
Hourly Rate
Validation of a method to analyze size distribution of crovalimab-complement C5-eculizumab complexes in human serum.
London, UK
2 hours ago
1 Received
- Crovalimab is a monoclonal antibody designed to target human complement C5, distinct from eculizumab, allowing for potential drug target complexes when switching between these medications.
- Researchers developed and validated a new analytical method to assess the size distribution of these drug-target-drug complexes using size-exclusion chromatography (SEC) and ELISA techniques.
- The validation of this DTDC assay method met acceptance criteria and enables further evaluation of how these complexes influence clinical outcomes for patients.
$100 - $150
Hourly Rate
Crovalimab for treatment of patients with paroxysmal nocturnal haemoglobinuria and complement C5 polymorphism: Subanalysis of the phase 1/2 COMPOSER study.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Characterization of multivalent complexes formed in the presence of more than one conventional antibody to terminal complement component C5.
London, UK
2 hours ago
1 Received
- - This study investigates how immune complexes form when patients are exposed to two different anti-C5 antibodies simultaneously, focusing on the transition from one treatment to another.
- - Researchers used size exclusion chromatography and multiangle light scattering to analyze the interactions between eculizumab and two other anti-C5 antibodies (TPP-2799 and TP-3544), both of which bind C5 similarly.
- - Results showed that when mixed with other antibodies, the complexes formed could exceed 1500 kDa, indicating multiple antibodies and C5 molecules interacting, suggesting the need for careful monitoring and strategies to prevent complex formation during such treatment transitions.
$100 - $150
Hourly Rate
Mitigating Drug-Target-Drug Complexes in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Switch C5 Inhibitors.
London, UK
2 hours ago
1 Received
- Drug-target-drug complexes (DTDCs) were observed in patients transitioning from eculizumab to crovalimab for treating paroxysmal nocturnal hemoglobinuria (PNH), due to the different ways these drugs bind to C5.
- In a phase I/II study, patients experienced transient reductions in crovalimab levels and the formation of DTDCs, with some mild hypersensitivity reactions noted.
- A mathematical model helped optimize crovalimab dosing, resulting in over a 50% reduction of large DTDCs and improved safety, showing that careful dosing can enhance treatment outcomes for patients using new antibody therapies.
$100 - $150
Hourly Rate
[COVID-19 development during the treatment of paroxysmal nocturnal hemoglobinuria].
London, UK
2 hours ago
1 Received
- Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder characterized by the breakdown of red blood cells due to a lack of complement regulators, leading to potentially severe hemolysis, especially during infections and thrombosis.
- A study in Japan reported five COVID-19 patients with PNH who were all vaccinated and treated with different medications for the condition.
- Despite experiencing mild to moderate COVID-19 symptoms and breakthrough hemolysis, none of the patients required oxygen or faced severe complications, and there were no thrombotic issues.
$100 - $150
Hourly Rate
Complement Inhibitors in the Management of Complement-Mediated Hemolytic Uremic Syndrome and Paroxysmal Nocturnal Hemoglobinuria.
London, UK
2 hours ago
1 Received
- CM-HUS and PNH are rare blood disorders linked to the malfunction of the complement system, traditionally treated with plasma exchange or supportive care, but emerging monoclonal antibodies offer better options.
- Eculizumab has been the main treatment for over ten years, but its administration challenges have led to the development of new therapies that enhance patient quality of life.
- Recent advancements include ravulizumab, which requires less frequent treatment, and other novel therapies currently in trials, showing promise for easier management of these conditions.
$100 - $150
Hourly Rate
Crovalimab treatment in patients with paroxysmal nocturnal haemoglobinuria: Long-term results from the phase I/II COMPOSER trial.
London, UK
2 hours ago
1 Received
- The study examined the long-term effects of crovalimab in patients with paroxysmal nocturnal hemoglobinuria as an extension of the COMPOSER trial, focusing on safety and drug effects.
- Out of 44 patients, 43 participated in the open-label extension (OLE) phase, with 32% experiencing treatment-related side effects, but overall, crovalimab's effectiveness was maintained.
- Findings indicated significant success in managing blood-related issues, such as haemoglobin stabilization and avoiding transfusions, confirming crovalimab's long-term tolerability and efficacy over a median treatment period of three years.
$100 - $150
Hourly Rate
Efficacy and safety of the C5 inhibitor crovalimab in complement inhibitor-naive patients with PNH (COMMODORE 3): A multicenter, Phase 3, single-arm study.
London, UK
2 hours ago
1 Received
- The COMMODORE 3 study tested a new drug, crovalimab, on patients with paroxysmal nocturnal hemoglobinuria (PNH) who had not been treated with complement inhibitors before.
- A total of 51 patients received crovalimab, with results showing 78.7% had control of hemolysis and 51% avoided blood transfusions after treatment.
- The drug was well-tolerated with no serious side effects leading to discontinuation, although there was one unrelated death; overall, crovalimab appears effective for treating PNH.
$100 - $150
Hourly Rate
Complement inhibitors in pediatric kidney diseases: new therapeutic opportunities.
London, UK
2 hours ago
1 Received
- The complement system is essential in the development of various kidney diseases, with significant activation evident through the consumption of complement proteins in serum and deposition in kidney tissues.
- The introduction of eculizumab has highlighted the potential of complement inhibitors to positively impact the progression of certain kidney diseases, leading to a surge in research and available treatments.
- This review discusses several key complement inhibitors, including eculizumab and others that have shown promise in clinical studies, demonstrating their effectiveness in reducing protein levels and stabilizing kidney function in a range of complement-related kidney conditions.
$100 - $150
Hourly Rate
Complement inhibition in paroxysmal nocturnal hemoglobinuria: From biology to therapy.
London, UK
2 hours ago
1 Received
- Complement inhibitors are key treatments for paroxysmal nocturnal hemoglobinuria (PNH), with eculizumab being the first drug that helped improve symptoms, though it requires lifelong intravenous infusions every two weeks.
- Ravulizumab, a newer drug, offers convenience by being administered every 8 weeks and helps improve hemolysis control, while other anti-C5 drugs and upstream inhibitors are under study and aim to address limitations of current treatments.
- Despite advancements, there remain challenges like drug adherence and managing breakthrough hemolysis (BTH) due to various physical stressors, highlighting the need for a more tailored treatment approach for PNH patients.
$100 - $150
Hourly Rate
Crovalimab: First Approval.
London, UK
2 hours ago
1 Received
- Crovalimab, developed by Chugai Pharmaceutical and Roche, is a monoclonal antibody targeting complement component C5, aimed at treating various complement-mediated diseases like PNH and lupus nephritis.
- The drug inhibits the cleavage of C5, blocking the complement pathway and preventing complications, and is designed for lower dosages with monthly subcutaneous administration.
- In early 2024, Crovalimab was approved in China for treating adolescents and adults with PNH, and it has also received approval in Japan while undergoing review in other countries including the USA and EU.
$100 - $150
Hourly Rate
A Cell-Based Assay to Measure the Activity of the Complement Convertases.
London, UK
2 hours ago
1 Received
- - The complement system is vital for defending against pathogens, but its dysregulation can lead to rare diseases, making it important to study the activity of complement convertases within the system.
- - This research introduces a novel assay using a human lymphoma cell line to evaluate the functional activity of complement convertases, utilizing specific blockers to control the cascade's progression.
- - The assay successfully detects overactivity in convertases and can differentiate between patients with harmful genetic variants and asymptomatic relatives, showcasing its potential for practical applications in nephrology.
$100 - $150
Hourly Rate
Navigating the Complement Pathway to Optimize PNH Treatment with Pegcetacoplan and Other Currently Approved Complement Inhibitors.
London, UK
2 hours ago
1 Received
- Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder caused by a mutation in hematopoietic stem cells that leads to a lack of protective proteins on red blood cells, making them vulnerable to destruction.
- The resulting symptoms include anemia, fatigue, and increased risk of blood clots due to complement-mediated hemolysis.
- Current treatments focus on inhibiting different stages of the complement activation pathway to manage symptoms and enhance patient outcomes, with pegcetacoplan being highlighted as a notable C3-targeted therapy.
$100 - $150
Hourly Rate