<unk>  has been in clinical trials for rheumatoid arthritis, autoimmune thrombocytopenia, autoimmune hemolytic anemia, IgA nephropathy, and lymphoma. The drug is currently being used in a Phase 1 trail to test the safety of the combination of the study drugs<unk>  and paclitaxel for patients with ovarian cancer. The investigation of<unk>  began with studies involving the treatment of mouse models with cytopenia. Mice were used to measure the effectiveness of R788, a small molecule prodrug of the biologically active R406, a Syk inhibitor. In animal models, treatment with R406/R788 was shown to be safe and effective in reducing inflammation and joint damage in immune-mediated rheumatoid arthritis. The models responded favorably to treatment so the study progressed to Phase 2 trials involving humans. Human studies have shown that R788 has good oral bioavailability, biologic activity, is well tolerated, and does not exhibit collagen or ADP-induced platelet aggregation. In NCT00706342, 16 adults with chronic ITP were entered into an open-label, single-arm cohort dose-escalation trials beginning with 75 mg and rising to 175 mg twice a day. The dose was increased until a persistent response was evident, toxicity was reached, or 175 mg twice a day was met. 8 patients achieved persistent responses with platelet counts greater than 50,000 mm3/L on more than 67% of their visits. 3 of these patients had not persistently responded to thrombopoietic agents. 4 others had nonsustained responses. Mean peak platelet count exceeded 100,000 mm3/L in these 12 patients. Toxicity was evidenced primarily in GI-related side effects, notable diarrhea, urgency, and vomiting. 2 patients developed transaminitis.<unk>  as a treatment for severe COVID19 complications has finished a Phase 2 trial, and is entering a Phase 3 trial. Rheumatoid arthritis A phase II study of rheumatoid arthritis patients failing to respond to a biologic agent showed little efficacy as compared to placebo, but the drug was well tolerated. In patients with high inflammatory burden, measured by levels of C-reactive protein, ACR20 was achieved by a significantly higher portion of those in the<unk>  group (42%) versus the placebo group (26%). Autoimmune thrombocytopenia Immune thrombocytopenic purpura (ITP) is an autoimmune disease where the immune system attacks and destroys platelets in the blood, causing abnormally low platelet counts. It is characterized by the antibody-mediated destruction of platelets. Patients with ITP have accelerated clearance of circulating IgG-coated platelets via Fcγ receptor-bearing macrophages in the spleen and liver, leading to different levels of thrombocytopenia and variable degrees of mucocutaneous bleeding. Recent studies of ITP pathophysiology suggest decreased platelet production may also be an important component of the thrombocytopenia. Many patients exhibit responses to established therapies, including corticosteroids, IV immunoglobulin, anti-D, splenectomy, and rituximab. However, there are a significant minority of patients who retain persistently low platelet counts despite treatment. These patients are consistently at risk of intracranial hemorrhage and other bleeding complications. Several thrombopoiesis-stimulating therapies including eltrombopag and romiplostim are being investigated to help combat low platelet counts in ITP patients. Rigel reported results from two Phase III clinical trials for<unk>  as an ITP treatment in August and October 2016. The study is the second Phase 3, multi-center, randomized, double-blind, placebo controlled, study of<unk>  disodium in the treatment of persistent/chronic immune thrombocytopenic purpura that Rigel has conducted. Primary outcome measures are defined as a stable platelet response by the end of the study (week 24) of at least 50,000/μL on at least 4 of the 6 visits between weeks 14–24. Participants received either a placebo, 100 mg, or 150 mg of the drug in the morning and evening for 24 full weeks. The first study, FIT 1 (047) met the primary endpoint in a statistically significant manner, with 18% of patients hitting the 50,000 platelets/μL of blood and no patients receiving the placebo meeting that criteria. As of June 2016, the open-label, long term extension study (049) is currently tracking 118 patients who opted to receive<unk>  after completing either study 047 or 048. Autoimmune hemolytic anemia Approval for treatment of autoimmune hemolytic anemia (AIHA) is in Stage 1 of Phase II trials. This study is a Phase 2, multi-center, open label, Simon two-stage study to evaluate the safety and efficacy of<unk>  disodium in the treatment of warm antibody autoimmune hemolytic anemia. Primary outcome measures examined include a hemoglobin response measured by levels higher than 10 g/dL and 2 g/dL higher than the baseline hemoglobin. Responses were studied for a period of 12 weeks and for a dose of 150 mg in the morning and evening. The study began in April 2016 and is estimated to conclude in September 2017. The study is currently recruiting participants from U.S. states including Arizona, California, D.C., Massachusetts, New York, North Carolina, and Texas. Subjects must have had a diagnosis of primary or secondary warm antibody AIHA, and must have failed at least 1 prior treatment regimen for AIHA. Subjects cannot have a platelet count less than 30,000/μL, have AIHA secondary to autoimmune disease, have uncontrolled or poorly controlled hypertension, or have cold antibody AIHA, cold agglutinin syndrome, mixed type AIHA, or paroxysmal cold hemoglobinuria. Immunoglobulin A nephropathy<unk>  as a treatment for IgA nephropathy (IgAN) is in Phase II trials, which will conclude at the end of 2016. IgAN is a chronic autoimmune disease associated with inflammation in the kidneys that reduces their ability to successfully filter blood. There are currently no disease-targeted therapies for IgAN. Participants are currently being recruited from the US, Austria, Germany, Hong Kong, Taiwan, and the UK. Patients must be between 18 and 70 years old, have renal biopsy findings consistent with IgA nephropathy, have been treated with an Angiotensin Converting Enzyme inhibitor (ACEi) and/or an Angiotensin II Receptor Blocker (ARB) for at least 90 days at the maximum approved dose, have a proteinuria > 1 gm/day at diagnosis of IgA nephropathy and a level > 0.5 gm/day at the second screening visit, and a blood pressure controlled to ≤ 1302/80 with angiotensin blockade. Eligible candidates cannot have recently used cyclophosphamide, mycophenolate mofetil, azathioprine, Rituximab, or > 15 mg/day of prednisone or any other corticosteroid equivalent. The study investigates whether<unk>  is a safe and effective treatment for IgAN. It is a Phase 2, multi-center, randomized, double-blind, ascending-dose, placebo-controlled clinical study. Primary outcome measures include the mean change in proteinuria as measured by spot urine protein/creatinine ratio (sPCR). Effects were evaluated for 100 mg, 150 mg, and placebo formulations taken twice daily by mouth for 24 weeks. The study began in October 2014 and is expected to complete by June 2017.
Fostamatinib
Tucatinib
Neratinib
Lapatinib
Ponatinib
Dasatinib
Pemigatinib
Capmatinib