Group 1 - Sanofi's investigational BTK inhibitor, rilzabrutinib, received orphan drug designation from the European Medicines Agency (EMA) for treating IgG4-related disease (IgG4-RD) [1][7] - IgG4-RD is a chronic, immune-mediated rare condition that can affect multiple organs, leading to inflammation, swelling, and fibrosis [1] - Rilzabrutinib is currently undergoing a phase II study for IgG4-RD, showing a reduction in disease flare and glucocorticoid sparing over 52 weeks [2][7] Group 2 - Rilzabrutinib is also being developed for immune thrombocytopenia (ITP) and has orphan drug designation for this indication in the United States, EU, and Japan [3] - A regulatory application for rilzabrutinib's approval for ITP is under review in the U.S., with a decision expected by August 29, 2025 [4] - The FDA has granted orphan drug designation to rilzabrutinib for warm autoimmune hemolytic anemia (wAIHA) and sickle cell disease (SCD) [5] Group 3 - Upon potential approval, rilzabrutinib may face competition from existing therapies, such as Rigel Pharmaceuticals' Tavalisse, which recorded $68.5 million in sales in the first half of 2025, a 44% increase year-over-year [6] - Amgen's Uplizna became the first FDA-approved drug for IgG4-RD in April 2025, following its acquisition of Horizon Therapeutics [8]

Core Insights - Sanofi's investigational BTK inhibitor, rilzabrutinib, has received orphan drug designation from the FDA for sickle cell disease (SCD), marking its fourth such indication [1][2][6] - Rilzabrutinib aims to reduce vaso-occlusive crises by modulating immune responses and has shown promising results in preclinical studies [1][3] - SCD affects over 100,000 individuals in the U.S., leading to severe complications and a significantly reduced life expectancy [4] Company Developments - Rilzabrutinib is currently under FDA review for immune thrombocytopenia (ITP), with a decision expected by August 29, 2025 [6][10] - The drug has also received orphan drug designation for treating warm autoimmune hemolytic anemia (wAIHA) and IgG4-related disease (IgG4-RD), both of which have significant unmet medical needs [7][9] - Sanofi's acquisition of Principia Biopharma included rilzabrutinib, which is also being developed for other immune-mediated diseases [11] Clinical Data - Preclinical studies indicate that rilzabrutinib effectively reduced vaso-occlusion and inflammation in SCD mouse models [3][6] - Phase IIb studies for wAIHA have shown clinically meaningful outcomes, while phase IIa studies for IgG4-RD demonstrated reductions in disease flare and other markers [8]

Core Viewpoint - The FDA has granted orphan drug designation to rilzabrutinib for sickle cell disease, highlighting its potential to address unmet medical needs in rare diseases [1][2]. Company Overview - Sanofi is an R&D driven biopharma company focused on improving lives through innovative medicines and vaccines, with a commitment to addressing urgent healthcare challenges [7]. Product Information - Rilzabrutinib is a novel, advanced, oral, reversible Bruton's tyrosine kinase (BTK) inhibitor that aims to restore immune balance through multi-immune modulation [5]. - The drug has received multiple orphan drug designations, including for immune thrombocytopenia (ITP), warm autoimmune hemolytic anemia (wAIHA), and IgG4-related disease (IgG4-RD) [2][8]. Disease Context - Sickle cell disease affects over 100,000 people in the US, predominantly impacting African American and Hispanic populations, leading to severe pain and reduced life expectancy [6]. - The disease is characterized by misshapen red blood cells that block blood flow, causing various health complications [6]. Regulatory Status - Rilzabrutinib is currently under regulatory review in the US, EU, and China for its potential use in ITP, with a target action date for FDA decision set for August 29, 2025 [3][8].

Core Insights - The U.S. FDA granted orphan drug designation to Sanofi SA's rilzabrutinib for two rare diseases: warm autoimmune hemolytic anemia (wAIHA) and IgG4-related disease (IgG4-RD) [1] - Rilzabrutinib is under regulatory review in the US, EU, and China for immune thrombocytopenia (ITP) [2] - The FDA's target action date for the regulatory decision on ITP is August 29, and rilzabrutinib has also received orphan drug designation for ITP in the US, EU, and Japan [3] Clinical Study Results - Phase 2b study results for wAIHA presented at ASH 2024 indicated that rilzabrutinib treatment led to clinically meaningful outcomes in response rate and disease markers [3] - In a phase 2a study for IgG4-RD, rilzabrutinib treatment over 52 weeks resulted in reduced disease flare and other disease markers, along with glucocorticoid sparing [4] - The safety profile of rilzabrutinib in both studies was consistent with previous studies [4] Recent Developments - The FDA recently approved Sanofi's Qfitlia (fitusiran), the first antithrombin-lowering therapy for hemophilia A or B, based on data from the ATLAS phase 3 studies [5] - Sanofi's stock increased by 3.54% to $55.86 during the premarket session following these developments [6]