06 Kidney-urinary system drugs
Lupus nephritis is the main cause of morbidity and death in patients with systemic lupus erythematosus (SLE). About 40% of patients with systemic lupus erythematosus will suffer from lupus nephritis at some point in the course of the disease. This process involves a variety of pathogenic mechanisms, including abnormal innate and adaptive immune responses, dysregulation of inflammatory signaling pathways, and increased cytokine production. In some SLE patients, renal involvement is benign and asymptomatic, but about 10%-30% of patients will progress to end-stage renal disease. Although this complication can have serious consequences, there are currently few satisfactory treatment options. Last year the FDA approved Belimumab (Benlysta; GlaxoSmithKline) as a new indication for lupus nephritis. The drug is an anti-TNFSF13B (Tumor Necrosis Factor Ligand Superfamily Member 13B; also known as B lymphocte stimulator or BLyS) monoclonal antibody. Belimumab has been on the market for nearly 10 years and has been used to treat adults and children with SLE. After the new indication was approved, it can be used to treat adult patients with active lupus nephritis who are receiving standard treatment.
07 Blood system disease drugs
Hypoxia-inducible factor (HIF) stabilizers are the latest treatment options for patients with anemia. HIF can regulate the expression of erythropoietin gene (EPO) in the kidney and liver. The oxygen-dependent degradation of HIF-1α is mediated by prolyl hydroxylation, which in turn can inhibit the expression of EPO in the liver and kidney. In recent years, a lot of HIF stabilizers have been developed. Such compounds exert therapeutic effect by inhibiting HIF prolyl hydroxylase (PHD). The design idea of these compounds is to stabilize and up-regulate the EPO gene transcription process, thereby stimulating endogenous red blood cell production and reversing anemia. The advantage of the small molecule HIF stabilizer is that it can exert the pharmacological activity of the drug through oral administration, thereby making it possible to treat anemia without the need for injection administration. Roxadustat, the first drug of this type of compound, was approved in 2019. In 2020, three other HIF stabilizers have been approved in Japan for the treatment of renal anemia, including Vadadadustat (Vafseo; Tanabe Mitsubishi Pharmaceuticals), Daprodustat (Duvroq; GlaxoSmithKline/Kyowa Kirin) and enarodustat (Enaroy; Japan Tobacco/Torii Pharmaceutical). Both Vadadadustat and Daprodustat are suitable for adult patients with or without dependence on dialysis; both drugs were launched in August; Enarodustat was approved in September and launched in December, and is suitable for the same broad patient population.
After the TGF-β inhibitory red blood cell maturation agent Luspatercept (Reblozyl; Acceleron Pharma/Celgene) was first approved for marketing in 2019 for the treatment of β-thalassemia, another indication was approved for marketing in 2020.It is used to treat patients with very low to intermediate risk myelodysplastic syndrome (MDS-RS) who have failed to treat anemia with an erythropoietin and require the infusion of ≥2 red blood cells within 8 weeks and have ring sideroblasts, or adult anemia patients with myelodysplastic/myeloproliferative tumors with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T). Luspatercept represents a new method of anemia treatment, that is, to help patients reduce the burden of RBC blood transfusion by regulating the later stages of red blood cell (RBC) maturation. In the MEDALIST phase III trial, in the first 24 weeks after the trial started, compared with the placebo group, the proportion of patients in the Luspatercept treatment group who achieved at least 8 weeks of independent red blood cell transfusion was significantly higher, reaching the primary endpoint of the study. In addition, in the first 24 and 48 weeks after the start of the study, compared with the placebo group, the proportion of patients in the treatment group who achieved at least 12 weeks of independent red blood cell transfusion was significantly higher.
In June 2019, the European Commission (EC) granted BluebirdBio’s Betibeg logenedarolentivec (Zynteglo) conditional marketing authorization, and this gene therapy is suitable for the treatment of non-β0/β0 genotype transfusion-dependent β-thalassemia (TDT) patients who are over 12 years old. These patients are suitable for hematopoietic stem cell transplantation (HSC), but they cannot receive transplantation because they cannot find a suitable HSC donor with human leukocyte antigen (HLA) matching. One-time gene therapy uses autologous CD34+ cells encoding the βA-T87Q-globulin gene to correct the underlying genetic causes of TDT, making it possible for patients who meet the treatment criteria to get rid of life-long blood transfusion dependence. Betibeglogene Darolentivec has obtained the priority review qualification of the EMAPRIME plan; it has also been selected as the pilot project of the EMA adaptability review. In the second half of 2019, Zynteglo’s refined production process was approved by EMA, paving the way for the drug to be launched in Germany in January 2020.
The bypass preparation Eptacogβ (Sevenfact) is a recombinant human coagulation factor VIIa analog expressed in rabbit milk that has been genetically engineered and was approved by the FDA last year for the treatment and control bleeding episodes in adults with hemophilia A or B who carry inhibitors and patients over 12 years of age. The active ingredient of Sevenfact is a recombinant analog of human factor FVII, expressed in genetically engineered rabbit mammary glands, and secreted into rabbit milk. FVII can be converted into activated FVII (FVIIa) during the purification and processing of rabbit milk. The bypass drug was jointly developed by the French biotechnology laboratory and HEMA Biologics for the US market.
Eosinophilia syndrome (HES) is a rare and underdiagnosed disease. HES patients will continue to produce a significant excess of eosinophils, which can make the number of such white blood cells up to three times the normal level. Eosinophils can cause inflammation and organ damage after infiltrating certain tissues; over time, it may affect the patient’s ability of daily life. Complications range from fever and discomfort to respiratory and cardiovascular diseases. Without treatment, the symptoms of HES will gradually worsen and may be life-threatening. Last year, the anti-interleukin-5 (IL-5) monoclonal antibody Mepolizumab (Nucala; GlaxoSmithKline) was approved by the FDA. The drug is used to treat HES adults and children ≥ 12 years old with a course of ≥ 6 months and no other clear non-hematological related causes. This indication is a new indication for this monoclonal antibody drug. The first approved indication for this drug is eosinophilic asthma and eosinophilic granuloma with polyangiitis (Churg-Strauss syndrome). The drug was granted orphan drug and fast-track qualifications, and received priority review.
08 Gastrointestinal drugs
The dopamine D2/D3 antagonist Amisulpride injection was approved by the FDA in February for the prevention and treatment of postoperative nausea and vomiting (PONV) in adult patients. Amisulpride is the first and only emergency antiemetic drug approved by PONV for patients who have previously failed to use standard therapies for prevention and treatment. The New Drug Application (NDA) included 4 phase III studies with data from more than 3,300 surgical patients and healthy volunteers. In a randomized, double-blind, placebo-controlled study in patients who were ineffective in the most commonly used antiemetic drugs, a single dose of Amisulpride 10 mg was significantly more effective in subjects than placebo ( 42%vs.29%).In a double-blind, randomized, placebo-controlled study in patients with the highest risk of PONV (Apfel score of 3 or 4), when both the Amisulpride 5mg single-dose group and the placebo group were given the same antiemetic drug, the Amisulpride group was significantly better than the placebo group in preventing PONV (58% vs. 47%). The drug was launched by Acacia Pharma in August under the trade name Barhemsys. At the end of 2019, RedHillBiopharma’s triple drug Talicia (omeprazole magnesium/amoxicillin/rifabutin) was approved by the FDA for the treatment of Helicobacter pylori infection in adults. Talicia is the only rifabutin-containing therapeutic drug approved for the treatment of Helicobacter pylori infection. Its drug design idea is to eliminate Helicobacter pylori based on the high resistance of the existing standard treatment of clarithromycin. Talicia was first listed in the United States in March 2020.