美国食品药监局（FDA）批准Vertex医药公司的Kalydeco用于治疗囊肿性纤维化疾病（CF）。
此次批准应用的对象是，拥有特异G551D基因变异的六岁及六岁以上的CF患者。实际上此次批准早于4月18号的处方药收费行为截止日期，主要是因为通过两个48周的在213名CF患者身上进行的研究显示，Kalydeco能够显著持续改善患者肺功能。
美国大约有3万名CF患者，是白种人中常见的一种致命基因型疾病，其中4%的患者患有G551D基因突变.
FDA会长MargaretHamburg说：“Kalydeco是一种非常好的治疗药。独特且互利的合作关系使得Kalydeco能够顺利获批，而对于参与研究的公司而言，也给他们提供了一种很好的模式。”
Lalydeco是由Vertex和非盈利组织CF治疗基金会共同研发的。
FDA中心负责药物评估和研发部主任JanetWoodcock说：“Kalydeco药片要和富含脂肪的食物一块服用，一天两次。这是一种突破性的治疗CF的药物，因为现有的治疗方法只能缓解症状。
Manufacturer:
Vertex Pharmaceuticals
Pharmacological Class:
Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator.
Active Ingredient(s):
Ivacaftor 150mg; tabs.
Indication(s):
Treatment of cystic fibrosis (CF) in patients ≥6 years who have a G551D mutation in the CFTR gene.
Pharmacology:
Ivacaftor is a potentiator of the CFTR protein. The CFTR protein is a chloride channel present at the surface of epithelial cells in multiple organs. Ivacaftor facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the G551D-CFTR protein.
Clinical Trials:
The efficacy of Kalydeco in patients with CF who have a G551D mutation in the CFTR gene was evaluated in two randomized, double-blind, placebo-controlled clinical trials in 213 patients with CF (109 receiving Kalydeco). All eligible patients from these trials were rolled over into an open-label extension study.
Trial 1 evaluated 161 patients with CF who were ≥12 years of age with baseline FEV1 between 40–90% predicted [mean FEV1 64% predicted (range: 32% to 98%)]. Trial 2 evaluated 52 patients who were 6–11 years with baseline FEV1 between 40%–105% predicted [mean FEV1 84% predicted (range: 44% to 134%)].
Patients in both trials were randomized 1:1 to receive either 150mg of Kalydeco or placebo every 12 hours with food containing fat for 48 weeks in addition to their prescribed CF therapies. The primary efficacy endpoint in both studies was improvement in lung function as determined by the mean absolute change from baseline in percent predicted pre-dose FEV1 through 24 weeks of treatment.
In both studies, treatment with Kalydeco resulted in a significant improvement in FEV1. The treatment difference between Kalydeco and placebo for the mean absolute change in percent predicted FEV1 from baseline through Week 24 was 10.6 percentage points (P<0.0001) in Trial 1 and 12.5 percentage points (P<0.0001) in Trial 2. These changes persisted through 48 weeks.
Legal Classification:
Rx
Adults & Children:
<6 years: not established. Take with fat-containing food (eg, eggs, butter, peanut butter, cheese pizza). ≥6 years: 150mg every 12 hours. Concomitant strong CYP3A inhibitors: 150mg twice weekly. Concomitant moderate CYP3A inhibitors: 150mg once daily. Moderate hepatic impairment: 150mg once daily. Severe hepatic impairment: 150mg once daily or less frequently.
Warnings/Precautions:
Not effective in patients with CF who are homozygous for the F508del mutation in the CFTR gene. Test for presence of the G551D mutation if genotype is unknown. Assess ALT/AST levels prior to initiating therapy, every 3 months during the first year of treatment, and annually thereafter. If increased ALT/AST levels develop, monitor closely until resolved. Interrupt dosing if ALT/AST is >5XULN; after resolution, consider restarting. Hepatic impairment. Severe renal impairment or ESRD. Pregnancy (Cat.B). Nursing mothers.
Interaction(s):
Concomitant strong CYP3A inducers (eg, rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, St. John’s Wort): not recommended. Potentiated by strong CYP3A inhibitors (eg, ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin) and moderate CYP3A inhibitors (eg, fluconazole, erythromycin). May be potentiated by grapefruit and Seville oranges; avoid. Potentiates CYP3A and/or P-gp substrates (eg, digoxin, cyclosporine, tacrolimus).
Adverse Reaction(s):
Headache, oropharyngeal pain, upper respiratory tract infection, nasal congestion, abdominal pain, nasopharyngitis, diarrhea, rash, nausea, dizziness.
How Supplied:
Tabs—60
Last Updated:
2/21/2012