ライフサイエンスコーパス: lumacaftor

1 Treatment with lumacaftor 200 mg once daily and ivacaftor 250 mg every

2 ozygous patients randomly assigned to either lumacaftor 200 mg once per day for 14 days followed by a

3 Patients (N = 58) received 200 mg lumacaftor/250 mg ivacaftor orally every 12 hours for 24

4 mg once per day group -8.9 mmol/L, p<0.001; lumacaftor 400 mg every 12 h group -10.3 mmol/L, p=0.002

5 groups was generally similar to that of the lumacaftor 400 mg every 12 h/ivacaftor 250 mg every 12 h

6 340 patients continued treatment with lumacaftor 400 mg every 12 h/ivacaftor 250 mg every 12 h

7 or TRAFFIC studies initiated treatment with lumacaftor 400 mg every 12 h/ivacaftor 250 mg every 12 h

8 e treatment groups between day 1 and day 56 (lumacaftor 400 mg once per day group -9.1 mmol/L, p<0.00

9 aily) plus ivacaftor (250 mg every 12 h), or lumacaftor (400 mg every 12 h) plus ivacaftor (250 mg ev

10 FFIC were randomly assigned (1:1) to receive lumacaftor (400 mg every 12 h)/ivacaftor (250 mg every 1

11 percentage points [1.7-3.8; p<0.0001] in the lumacaftor [400 mg/12 h]-ivacaftor group).

12 percentage points [0.2-6.4; p=0.036] in the lumacaftor [400 mg/12 h]-ivacaftor group).

13 The efficacy and safety profile of the lumacaftor 600 mg once daily/ivacaftor 250 mg every 12 h

14 mg once per day group -9.1 mmol/L, p<0.001; lumacaftor 600 mg once per day group -8.9 mmol/L, p<0.00

15 In cohort 2, the lumacaftor 600 mg once per day significantly improved FE

16 nts were randomly assigned to receive either lumacaftor (600 mg once daily or 400 mg every 12 hours)

17 response system (1:1:1) to receive placebo, lumacaftor (600 mg once daily) plus ivacaftor (250 mg ev

18 every 12 h)/ivacaftor (250 mg every 12 h) or lumacaftor (600 mg once daily)/ivacaftor (250 mg every 1

19 percentage points [2.3-4.4; p<0.0001] in the lumacaftor [600 mg per day]-ivacaftor group and 2.8 perc

20 tage points [95% CI 0.5-6.9; p=0.024] in the lumacaftor [600 mg/day]-ivacaftor group and 3.3 percenta

21 mbining ivacaftor (a gating potentiator) and lumacaftor (a folding corrector) have proven efficacious

22 tightness or dyspnoea during treatment with lumacaftor alone.

23 We tested combination treatment with lumacaftor, an investigational CFTR corrector that incre

24 active web response system to receive 200 mg lumacaftor and 250 mg ivacaftor every 12 hours or placeb

25 re enrolled and randomly assigned to receive lumacaftor and ivacaftor (n=104) or placebo (n=102).

26 103 patients received at least one dose of lumacaftor and ivacaftor and 101 patients received at le

27 treptococcal throat infection and one in the lumacaftor and ivacaftor arm due to withdrawal based on

28 pport the further exploration of combination lumacaftor and ivacaftor as a treatment in this setting.

29 We conclude that chronic lumacaftor and ivacaftor co-treatment restores stability

30 Lumacaftor and ivacaftor combination treatment showed ef

31 bation of F508del-CFTR-expressing cells with lumacaftor and ivacaftor deactivated macroscopic F508del

32 reported in 13 (13%) of 103 patients in the lumacaftor and ivacaftor group and 11 (11%) of 101 patie

33 events in three (3%) of 103 patients in the lumacaftor and ivacaftor group and two (2%) of 101 patie

34 We provide evidence that combination lumacaftor and ivacaftor improves FEV1 for patients with

35 We report efficacy and safety of lumacaftor and ivacaftor in patients with cystic fibrosi

36 units (95% CI -1.43 to -0.75, p<0.0001) for lumacaftor and ivacaftor versus placebo.

37 INTERPRETATION: Treatment with lumacaftor and ivacaftor was associated with statistical

38 consistent with previous phase 3 studies of lumacaftor and ivacaftor.

39 Two small molecules, the CFTR corrector lumacaftor and the potentiator ivacaftor, are now used c

40 1 was used in combination with the corrector lumacaftor and the potentiator ivacaftor, it showed an a

41 ents, randomly assigned to either 56 days of lumacaftor (cohort 2: 200 mg, 400 mg, or 600 mg once per

42 These data show that lumacaftor in combination with ivacaftor provided a bene

43 adverse events was generally similar in the lumacaftor-ivacaftor and placebo groups.

44 mprovements in the primary end point in both lumacaftor-ivacaftor dose groups; the difference between

45 of intravenous antibiotics was lower in the lumacaftor-ivacaftor groups as well.

46 ary exacerbations was 30 to 39% lower in the lumacaftor-ivacaftor groups than in the placebo group; t

47 e event was 4.2% among patients who received lumacaftor-ivacaftor versus 1.6% among those who receive

48 These analyses confirm that lumacaftor/ivacaftor combination therapy benefits patien

49 Lumacaftor/ivacaftor combination therapy has shown clini

50 erability, pharmacodynamics, and efficacy of lumacaftor/ivacaftor combination therapy in patients age

51 ERPRETATION: The long-term safety profile of lumacaftor/ivacaftor combination therapy was consistent

52 The long-term safety profile of lumacaftor/ivacaftor combination therapy was consistent

53 The 24-week safety and efficacy of lumacaftor/ivacaftor combination therapy was shown in tw

54 ry exacerbation events were observed in both lumacaftor/ivacaftor dose groups compared with placebo a

55 at week 24 in ppFEV1 were observed with both lumacaftor/ivacaftor doses in the subgroup with baseline

56 RATIONALE: Combination lumacaftor/ivacaftor has been shown to improve lung func

57 e respiratory adverse events was higher with lumacaftor/ivacaftor than with placebo in all subgroups.

58 e aimed to assess the efficacy and safety of lumacaftor/ivacaftor therapy in these patients, defined

59 he long-term safety and efficacy of extended lumacaftor/ivacaftor therapy in this group of patients i

60 generally similar to that observed in larger lumacaftor/ivacaftor trials with older patients.

61 be observed with longer-term treatment, and lumacaftor/ivacaftor was associated with a 42% slower ra

62 Lumacaftor/ivacaftor was well tolerated in this young po

63 Lumacaftor/ivacaftor was well tolerated; the safety prof

64 alised rate of ppFEV1 decline was reduced in lumacaftor/ivacaftor-treated patients compared with matc

65 Lumacaftor partially stabilized purified full-length F50

66 2 knockdown with the corrector drug, VX-809 (lumacaftor) restored the mutant function to ~50% of the

67 that were designed to assess the effects of lumacaftor (VX-809), a CFTR corrector, in combination wi

68 y distinct correctors, corrector 4a (C4) and lumacaftor (VX-809), on I507-ATT and I507-ATC DeltaF508