CFB

PASADENA, CA, USA I December 21, 2023 I Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today announced that it has filed an application for clearance to initiate a Phase 1/2a clinical trial of ARO-CFB, the company’s investigational RNA interference (RNAi) therapeutic being developed as a potential treatment for complement mediated renal disease, such as immunoglobulin A nephropathy (IgAN), which is the most common glomerular disease worldwide and carries a high lifetime risk of progression to end-stage renal disease. Additionally, ARO-CFB may have clinical applications in non-renal diseases involving complement activation. ARO-CFB is designed to reduce hepatic expression of complement factor B (CFB), which plays an important regulatory role in amplifying complement alternative pathway activation and has been identified as a promising therapeutic target. James Hamilton, M.D., MBA, Chief of Discovery and Translational Medicine at Arrowhead, said: “IgAN is the most common glomerular disease worldwide, accounting for up to 40% of all cases of glomerulonephritis. Our preclinical studies have demonstrated that ARO-CFB can achieve deep and durable reductions in liver production of CFB, which plays a key role in the activation of the alternative complement pathway associated with the pathogenesis of renal disease in IgAN. As the liver is the main site of CFB production and our TRiM TM system has consistently demonstrated the ability to silence liver production of target gene products across several candidates, we believe ARO-CFB has the potential to be a powerful treatment option for complement mediated renal disease.” An application for approval of the clinical trial was submitted to a local Ethics Committee and to the New Zealand Medicines and Medical Devices Safety Authority for review by the Standing Committee on Therapeutic Trials. Pending clearance, Arrowhead intends to proceed with AROCFB-1001, a Phase 1/2a dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ARO-CFB in up to 66 healthy volunteers and patients with complement mediated kidney disease. About Arrowhead Pharmaceuticals Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing. For more information, please visit www.arrowheadpharma.com , or follow us on X (formerly Twitter) at @ArrowheadPharma or on LinkedIn . To be added to the Company's email list and receive news directly, please visit http://ir.arrowheadpharma.com/email-alerts . SOURCE: Arrowhead Pharmaceuticals

Ad hoc announcement pursuant to Art. 53 LR Approval based on APPLY-PNH trial in adults with PNH and anemia despite prior anti-C5 treatment, and supported by the APPOINT-PNH study in complement inhibitor-naïve patients1-5 In APPLY-PNH, patients who switched to Fabhalta experienced superior increases of hemoglobin levels ≥ 2 g/dL (82.3% vs. 0%) and hemoglobin level ≥ 12 g/dL (67.7% vs. 0%), both in the absence of red blood cell transfusions, vs. patients who continued on anti-C5 treatment1,2 Fabhalta, now available for both previously treated and treatment-naïve patients, is the only FDA-approved Factor B inhibitor of the immune system’s complement pathway, which drives complement-mediated hemolysis in PNH1,6 Significant unmet need remains in PNH, a chronic and rare blood disorder; despite anti-C5 therapy, a large proportion of patients can remain anemic and dependent on blood transfusions7,8 Late-stage Fabhalta development program ongoing in multiple complement-mediated conditions Novartis today announced that the U.S. Food and Drug Administration (FDA) approved Fabhalta® (iptacopan) as the first oral monotherapy for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH)1. Fabhalta is a Factor B inhibitor that acts proximally in the alternative complement pathway of the immune system, providing comprehensive control of red blood cell (RBC) destruction within and outside the blood vessels (intra- and extravascular hemolysis [IVH and EVH]). In clinical trials, treatment with Fabhalta increased hemoglobin levels (≥ 2 g/dL from baseline in the absence of RBC transfusions) in the majority of patients and in APPLY-PNH nearly all patients treated with Fabhalta did not receive blood transfusions1-5. “An efficacious oral treatment with a demonstrated safety profile could be practice-changing for physicians and help relieve burdens experienced by people with PNH,” said Vinod Pullarkat, MD, MRCP, Clinical Professor, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope. “In clinical studies, iptacopan was superior to anti-C5s in hemoglobin improvement in the absence of RBC transfusion and transfusion avoidance rate, and also effective in complement inhibitor-naïve individuals, by providing clinically meaningful hemoglobin-level increases without the need for blood transfusions.” The FDA approval is based on the Phase III APPLY-PNH trial in patients with residual anemia (hemoglobin 1,2. Approval was also supported by the Phase III APPOINT-PNH study in complement inhibitor-naïve patients1,3. The 24-week core treatment periods in APPLY-PNH and APPOINT-PNH trials respectively showed1-3: Patients with sustained increase of hemoglobin levels ≥ 2 g/dLa from baseline in the absence of transfusions: 82.3% of anti-C5-experienced Fabhalta patients responded vs. 0% for anti-C5 (difference of 81.5%b, Pc)1-3. Patients with sustained hemoglobin level ≥ 12 g/dLa in the absence of transfusions: 67.7% of anti-C5-experienced Fabhalta patients responded vs. 0% for anti-C5 (difference of 66.6%b, P1,2. Patients avoiding transfusiond,e: Transfusion avoidance rate 95.2% for anti-C5-experienced Fabhalta patients vs. 45.7% for anti-C5 (difference of 49.5%b, P1,2. In the APPLY-PNH trial, the most commonly reported (≥10%) adverse reactions (ARs) with Fabhalta vs. anti-C5s were: headachef (19% vs. 3%), nasopharyngitisg (16% vs. 17%), diarrhea (15% vs. 6%), abdominal painf (15% vs. 3%), bacterial infectionh (11% vs. 11%), nausea (10% vs. 3%), and viral infectioni (10% vs. 31%)1,2. In the APPOINT-PNH trial, the most commonly reported ARs (≥10%) were headachef (28%), viral infectioni (18%), nasopharyngitisg (15%), and rashj (10%)1,3. In APPLY-PNH, serious ARs were reported in two (3%) patients with PNH receiving Fabhalta, which included pyelonephritis, urinary tract infection and COVID-191,2. In APPOINT-PNH, serious ARs were reported in two (5%) patients with PNH receiving Fabhalta, which included COVID-19 and bacterial pneumonia1,3. Fabhalta may cause serious infections caused by encapsulated bacteria and is available only through a Risk Evaluation and Mitigation Strategy (REMS) that requires vaccinations for encapsulated bacteria1. People with PNH have an acquired mutation making red blood cells susceptible to premature destruction by the complement system6,8. PNH is characterized by hemolysis, bone marrow failure, and thrombosis in varying combinations and levels of severity6-8. Existing C5 inhibitor treatments, administered as infusions, may leave PNH symptoms uncontrolled7,8. Up to 88% of patients on anti-C5 treatment may have persistent anemia with over one-third of those patients requiring blood transfusions at least once per year7,8. “The U.S. approval of Fabhalta is an extraordinary moment for people living with PNH, their loved ones and the healthcare providers who care for them,” said Victor Bultó, President US, Novartis. “This new, effective oral medicine may mean that patients can reset their expectations of living with PNH, a chronic and life-altering blood disease. As Novartis continues to focus on conditions with unmet patient need, we are exploring the potential of Fabhalta in other complement-mediated diseases – with an ultimate goal to drive meaningful change for patients.” Discovered and developed by Novartis, Fabhalta is expected to be available in the United States in December. Additional regulatory filings and reviews for Fabhalta in PNH are currently underway around the world. Assessed between Day 126 and Day 168. bAdjusted difference in proportion. cSensitivity analysis incorporates data from local labs when central labs were not available. dAssessed between Day 14 and Day 168. eTransfusion avoidance is defined as absence of administration of packed-red blood cell transfusions between Day 14 and Day 168. fIncludes similar terms. gNasopharyngitis contains: rhinitis allergic, upper respiratory tract infection, pharyngitis, rhinitis. hBacterial infection contains: pyelonephritis, urinary tract infection, bronchitis bacterial, bronchitis haemophilus, cholecystitis, folliculitis, cellulitis, arthritis bacterial, sepsis, klebsiella infection, staphylococcal infection, Pseudomonas infection, hordeolum, pneumonia bacterial. iViral infection contains: COVID-19, herpes zoster, oral herpes, nasal herpes, influenza A virus test positive, influenza. jRash: dermatitis allergic, acne, erythema multiforme, rash maculo-papular, rash erythematous. APPLY-PNH (NCT04558918) was a Phase III, randomized, multinational, multicenter, active-comparator controlled, open-label trial to evaluate the efficacy and safety of twice-daily, oral Fabhalta monotherapy (200 mg) for the treatment of PNH by assessing if switching to Fabhalta was superior to continuing on anti-C5 therapies (US-approved and non-US-approved eculizumab and ravulizumab) in adult patients presenting with residual anemia (Hb 2,9. The trial enrolled 97 patients who were randomized in an 8:5 ratio to either twice-daily, oral Fabhalta monotherapy, or intravenous anti-C5 therapies (continuing with the same regimen as they were on prior to randomization)2,9. APPOINT-PNH (NCT04820530) was a Phase III, multinational, multicenter, open-label, uncontrolled single-arm study to evaluate the efficacy and safety of twice-daily, oral Fabhalta monotherapy (200 mg) in adult PNH patients who are naïve to complement inhibitor therapy, including anti-C5 therapies (eculizumab or ravulizumab)3,10. The trial enrolled 40 patients who received twice-daily, oral Fabhalta monotherapy3,10. PNH is a rare, chronic and serious complement-mediated blood disorder6. People with PNH have an acquired mutation in some of their hematopoietic stem cells (which are located in the bone marrow and can grow and develop into RBCs, white blood cells and platelets) that causes them to produce RBCs that are susceptible to premature destruction by the complement system6,8. This leads to intravascular hemolysis (destruction of RBCs within blood vessels) and extravascular hemolysis (destruction of RBCs mostly in the spleen and liver), which cause anemia (low levels of circulating RBCs), thrombosis (formation of blood clots) and other debilitating symptoms6,8. It is estimated that approximately 10-20 people per million worldwide live with PNH6. Although PNH can develop at any age, it is often diagnosed in people between 30-40 years old11,12. PNH has a significant unmet need not fully addressed by anti-C5 therapies (eculizumab or ravulizumab): despite treatment with anti-C5s, a large proportion of people with PNH may remain anemic, and dependent on blood transfusions6-8,13,14. Fabhalta (iptacopan) is an oral, Factor B inhibitor of the alternative complement pathway15-17. Fabhalta is indicated for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH). Discovered at Novartis, Fabhalta is currently in development for a range of complement-mediated diseases including immunoglobulin A nephropathy (IgA nephropathy), C3 glomerulopathy (C3G), immune complex membranoproliferative glomerulonephritis (IC-MPGN) and atypical hemolytic uremic syndrome (aHUS). Based on disease prevalence, unmet needs and data from Phase II studies, Fabhalta has received FDA Breakthrough Therapy Designation in PNH, FDA Breakthrough Therapy Designation in C3G, orphan drug designations from the FDA and EMA in PNH and C3G, EMA PRIME designation for C3G, and EMA orphan drug designation in IgAN18-21. Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide. References Iptacopan Prescribing Information. East Hanover, NJ: Novartis Pharmaceuticals Corp; December 2023. Risitano AM, Rӧth A, Kulasekararaj A, et al. Oral Iptacopan Monotherapy Has Superior Efficacy to Anti-C5 Therapy in Patients with Paroxysmal Nocturnal Hemoglobinuria and Residual Anemia: Results From the Phase III APPLY-PNH Study. Presented at: 49th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT); April 23-36, 2023; Paris, France. Risitano AM, Han B, Ueda Y, et al. Oral Complement Factor B Inhibitor Iptacopan Monotherapy Improves Hemoglobin to Normal/Near-Normal Levels in Paroxysmal Nocturnal Hemoglobinuria Patients Naïve to Complement Inhibitors: Phase III APPOINT-PNH Trial. Presented at: 49th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT); April 23-36, 2023; Paris, France. Risitano AM, Röth A, Soret J, et al. Addition of iptacopan, an oral factor B inhibitor, to eculizumab in patients with paroxysmal nocturnal haemoglobinuria and active haemolysis: an open-label, single-arm, phase 2, proof-of-concept trial. Lancet Haematol. 2021;8(5):e344-e354. doi:10.1016/S2352-3026(21)00028-4 Jang JH, Wong L, Ko BS, et al. Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria: a 2-cohort open-label proof-of-concept study. Blood Adv. 2022;6(15):4450-4460. doi:10.1182/bloodadvances.2022006960 Cançado RD, Araújo A da S, Sandes AF, et al. Consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria. Hematol Transfus Cell Ther. 2021;43(3):341-348. doi:10.1016/j.htct.2020.06.006 McKinley CE, Richards SJ, Munir T, et al. Extravascular Hemolysis Due to C3-Loading in Patients with PNH Treated with Eculizumab: Defining the Clinical Syndrome. Blood. 2017;130(Supplement 1):3471. doi:10.1182/blood.V130.Suppl_1.3471.3471 Dingli D, Matos JE, Lehrhaupt K, et al. The burden of illness in patients with paroxysmal nocturnal hemoglobinuria receiving treatment with the C5-inhibitors eculizumab or ravulizumab: results from a US patient survey. Ann Hematol. 2022;101(2):251-263. doi:10.1007/s00277-021-04715-5 Novartis Pharmaceuticals. A Randomized, Multicenter, Active-Comparator Controlled, Open-Label Trial to Evaluate Efficacy and Safety of Oral, Twice Daily LNP023 in Adult Patients With PNH and Residual Anemia, Despite Treatment With an Intravenous Anti-C5 Antibody. clinicaltrials.gov; 2022. Accessed September 21, 2022. https://clinicaltrials.gov/ct2/show/NCT04558918 Novartis Pharmaceuticals. A Multicenter, Single-Arm, Open-Label Trial to Evaluate Efficacy and Safety of Oral, Twice Daily Iptacopan in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy. clinicaltrials.gov; 2022. Accessed September 21, 2022. https://clinicaltrials.gov/ct2/show/NCT04820530 Hill A, DeZern AE, Kinoshita T, Brodsky RA. Paroxysmal nocturnal haemoglobinuria. Nat Rev Dis Primer. 2017;3(1):17028. doi:10.1038/nrdp.2017.28 Schrezenmeier H, Röth A, Araten DJ, et al. Baseline clinical characteristics and disease burden in patients with paroxysmal nocturnal hemoglobinuria (PNH): updated analysis from the International PNH Registry. Ann Hematol. 2020;99(7):1505-1514. doi:10.1007/s00277-020-04052-z Debureaux PE, Kulasekararaj AG, Cacace F, et al. Categorizing hematological response to eculizumab in paroxysmal nocturnal hemoglobinuria: a multicenter real-life study. Bone Marrow Transplant. 2021;56(10):2600-2602. doi:10.1038/s41409-021-01372-0 Debureaux PE, Cacace F, Silva BGP, et al. Hematological Response to Eculizumab in Paroxysmal Nocturnal Hemoglobinuria: Application of a Novel Classification to Identify Unmet Clinical Needs and Future Clinical Goals. Blood. 2019;134(Supplement_1):3517-3517. doi:10.1182/blood-2019-125917 Schubart A, Anderson K, Mainolfi N, et al. Small-molecule factor B inhibitor for the treatment of complement-mediated diseases. Proc Natl Acad Sci. 2019;116(16):7926-7931. doi:10.1073/pnas.1820892116 Barratt J, Rovin B, Zhang H, et al. POS-546 EFFICACY AND SAFETY OF IPTACOPAN IN IgA NEPHROPATHY: RESULTS OF A RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED PHASE 2 STUDY AT 6 MONTHS. Kidney Int Rep. 2022;7(2):S236. doi:10.1016/j.ekir.2022.01.577 Rizk DV, Rovin BH, Zhang H, et al. Targeting the Alternative Complement Pathway With Iptacopan to Treat IgA Nephropathy: Design and Rationale of the APPLAUSE-IgAN Study. Kidney Int Rep. 2023;8(5):968-979. doi:10.1016/j.ekir.2023.01.041 The content above comes from the network. if any infringement, please contact us to modify.

DUBLIN, Nov. 22, 2023 /PRNewswire/ -- The "Danicopan Emerging Drug Insight and Market Forecast - 2032" report has been added to ResearchAndMarkets.com's offering. This "Danicopan Emerging Drug Insight and Market Forecast - 2032" report provides comprehensive insights about danicopan for paroxysmal nocturnal hemoglobinuria (PNH) in the seven major markets. A detailed picture of the danicopan for PNH in the 7MM, i.e., the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan for the study period 2019 -2032 is provided in this report along with a detailed description of the danicopan for PNH. The report provides insights about mechanism of action, dosage and administration, as well as research and development including regulatory milestones, along with other developmental activities. Further, it also consists of future market assessments inclusive of the danicopan market forecast analysis for PNH in the 7MM, SWOT, analysts' views, comprehensive overview of market competitors, and brief about other emerging therapies in PNH. Drug Summary ALXN2040 (also known as danicopan) is an investigational, first-in-class, oral proximal factor D inhibitor developed by Achillion, a wholly owned subsidiary of Alexion. Factor D (FD), a serine protease, catalyzes the cleavage of complement factor B into Ba and Bb, which allows for the formation of the AP C3 convertase. By inhibiting FD, danicopan, blocks C3 convertase formation, the control point for AP activation, and the amplification of all pathways. This leads to the inhibition of C3 cleavage, C3 fragment deposition, terminal pathway activation, and MAC formation. The drug has already received Breakthrough Therapy Designation (BTD) and Orphan Drug Designation (ODD) by the FDA and PRIME designation and ODD by the EMA. Phase III development is currently being initiated for danicopan as an add-on therapy for PNH patients with extravascular hemolysis (EVH). Besides, the company is conducting Phase II studies to determine the effectiveness of ACH-0144471 in patients with PNH who have an inadequate response to eculizumab monotherapy. In-depth Danicopan Market Assessment This report provides a detailed market assessment of danicopan for paroxysmal nocturnal hemoglobinuria (PNH) in the seven major markets, i.e., the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan. This segment of the report provides forecasted sales data from 2024 to 2032. Danicopan Clinical Assessment The report provides the clinical trials information of danicopan for PNH covering trial interventions, trial conditions, trial status, start and completion dates. Report Highlights In the coming years, the market scenario for paroxysmal nocturnal hemoglobinuria (PNH) is set to change due to the extensive research and incremental healthcare spending across the world; which would expand the size of the market to enable the drug manufacturers to penetrate more into the market. The companies are developing therapies that focus on novel approaches to treat/improve the disease condition, assess challenges, and seek opportunities that could influence danicopan dominance. Other emerging products for PNH are expected to give tough market competition to danicopan and launch of late-stage emerging therapies in the near future will significantly impact the market. A detailed description of regulatory milestones, and developmental activities, provide the current development scenario of danicopan in PNH. This in-depth analysis of the forecasted sales data of danicopan from 2024 to 2032 will support the clients in the decision-making process regarding their therapeutic portfolio by identifying the overall scenario of the danicopan in PNH. Key Topics Covered: 1. Report Introduction 2. Danicopan Overview in PNH 2.1. Product Detail 2.2. Clinical Development 2.2.1. Clinical studies 2.2.2. Clinical trials information 2.2.3. Safety and efficacy 2.3. Other Developmental Activities 2.4. Product Profile 3. Competitive Landscape (Marketed Therapies) 4. Competitive Landscape (Late-stage Emerging Therapies) 5. Danicopan Market Assessment 5.1. Market Outlook of Danicopan in PNH 5.2. 7MM Analysis 5.2.1. Market Size of Danicopan in the 7MM for PNH 5.3. Country-wise Market Analysis 5.3.1. Market Size of Danicopan in the United States for PNH 5.3.2. Market Size of Danicopan in Germany for PNH 5.3.3. Market Size of Danicopan in France for PNH 5.3.4. Market Size of Danicopan in Italy for PNH 5.3.5. Market Size of Danicopan in Spain for PNH 5.3.6. Market Size of Danicopan in the United Kingdom for PNH 5.3.7. Market Size of Danicopan in Japan for PNH 6. SWOT Analysis 7. Analysts' Views 8. Appendix For more information about this report visit About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends. Media Contact: Research and Markets Laura Wood, Senior Manager [email protected] For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900 U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716 Logo: SOURCE Research and Markets