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Date: 2018-07-26

Type of information: Positive opinion for the granting of a Market Authorisation in the EU

Product name: Kalydeco®

Compound: ivacaftor

Therapeutic area: Rare diseases - Genetic diseases

Action mechanism:

  • CFTR potentiator. Ivacaftor is an oral agent that increases ion-function of activated cell-surface cystic fibrosis transmembrane conductance regulator (CFTR).  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.  In vitro, ivacaftor increased CFTR-mediated transepithelial current (IT) in rodent cells expressing G551D-CFTR protein following addition of a cyclic adenosine monophosphate (cAMP) agonist with an EC50 of 100 ± 47 nM; however, ivacaftor did not increase IT in the absence of cAMP agonist. Ivacaftor also increased IT in human bronchial epithelial cells expressing G551D-CFTR protein following addition of a cAMP agonist with an EC50 of 236 nM. Ivacaftor increased the open probability of G551D-CFTR protein in single channel patch clamp experiments using membrane patches from rodent cells expressing G551D-CFTR protein by 10-fold versus untreated cells after addition of PKA and ATP.
  • Kalydeco® was first approved by the FDA in January 2012 for use in people with CF ages 6 and older who have at least one copy of the G551D mutation and in February 2014 for use in people with CF ages 6 and older who have the following additional CFTR mutations: G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P and G1349D. It was approved by the European Medicines Agency in July 2012, by Health Canada in November 2012 and by the Therapeutic Goods Administration in Australia in July 2013 for use in people with CF ages 6 and older who have at least one copy of the G551D mutation in the CFTR gene.
 

Company: Vertex Pharmaceuticals (USA - MA)

Disease:

  • cystic fibrosis for people ages 6 and older and in children ages 2 to 5 with cystic fibrosis (CF) who have one of 10 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R and R117H)
  • cystic fibrosis in children ages 2 and older who have one of 23 residual function mutations in the CFTR gene
  • cystic fibrosis in children ages 2 and older who have one of five residual function mutations that result in a splicing defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene  (2789+5G— > A, 3272-26A— > Gi
  • n a combination regimen with tezacaftor 100 mg/ivacaftor 150 mg tablets for the treatment of patients with cystic fibrosis  aged 12 years and older who are homozygous for the F508del mutation or who are heterozygous for the F508del mutation and have one of the following mutations in the CFTR gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A?G, S945L, S977F, R1070W, D1152H, 2789+5G?A, 3272-26A?G, and 3849+10kbC?T., 3849+10kbC— > T, 711+3A— > G, and E831X)

Latest news:

  • • On 26 July 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a change to the terms of the marketing authorisation for Kalydeco®. The committee adopted an extension to the existing indication as follows: “Kalydeco® tablets are also indicated in a combination regimen with tezacaftor 100 mg/ivacaftor 150 mg tablets for the treatment of patients with cystic fibrosis (CF) aged 12 years and older who are homozygous for the F508del mutation or who are heterozygous for the F508del mutation and have one of the following mutations in the CFTR gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A?G, S945L, S977F, R1070W, D1152H, 2789+5G?A, 3272-26A?G, and 3849+10kbC?T.
  • Kalydeco® tablets are also indicated for the treatment of patients with cystic fibrosis aged 18 years and older who have an R117H mutation in the CFTR gene
  • Kalydeco® tablets are also indicated in a combination regimen with tezacaftor 100 mg/ivacaftor 150 mg tablets for the treatment of patients with cystic fibrosis  aged 12 years and older who are homozygous for the F508del mutation or who are heterozygous for the F508del mutation and have one of the following mutations in the CFTR gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A?G, S945L, S977F, R1070W, D1152H, 2789+5G?A, 3272-26A?G, and 3849+10kbC?T. Detailed recommendations for the use of this product will be described in the updated summary of 1 Summaries of positive opinion are published without prejudice to the Commission decision, which will normally be issued 67 days from adoption of the opinion 2 New text in bold Kalydeco EMA/506642/2018 Page 2/2 product characteristics (SmPC), which will be published in the revised European public assessment report (EPAR), and will be available in all official European Union languages after a decision on this change to the marketing authorisation has been granted by the European Commission.
  • • On August 1, 2017, Vertex Pharmaceuticals announced that the FDA has approved Kalydeco® (ivacaftor) for use in more than 600 people with cystic fibrosis  ages 2 and older who have one of five residual function mutations that result in a splicing defect in the CFTR gene. This approval was based on Phase 3 clinical data for Kalydeco® in these mutations and follows the FDA's approval of Kalydeco® in May 2017 for 23 other residual function mutations, which was based on analyses of in vitro data.  The five mutations covered under this new approval (2789+5G— > A, 3272-26A— > G, 3849+10kbC— > T, 711+3A— > G, and E831X) cause CF and result in a moderate loss of chloride transport. People who have these mutations generally experience progressive lung function decline and other complications of the disease. All five of these mutations were evaluated as part of the previously disclosed Phase 3 EXPAND study. Kalydeco® is now approved in the U.S. to treat people with CF ages 2 and older who have one of 38 ivacaftor-responsive
  • • On June 1, 2017, Vertex Pharmaceuticals announced it has reached an agreement with the Health Service Executive (HSE) in the Republic of Ireland to expand access to Kalydeco® (ivacaftor) for children ages 2 to 5 with any approved gating mutation (G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P and G1349D) and to people ages 18 and older who have an R117H mutation. These reimbursements are effective immediately. This innovative long-term agreement also enables rapid access for people with these mutations if the labels of the existing medicines are expanded to cover additional age groups and if new Vertex medicines are approved for these populations.
  • • On May 17, 2017, Vertex Pharmaceuticals announced that the FDA has approved Kalydeco® (ivacaftor) for use in people with cystic fibrosis (CF) ages 2 and older who have one of 23 residual function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This decision is based on analyses of in vitro data and is supported by more than five years of real-world clinical data that demonstrate Kalydeco®'s strong safety and efficacy profile. More than 900 people ages 2 and older in the U.S. have one of these mutations. Based on this approval, Vertex today increased its guidance for 2017 product revenues of Kalydeco® to a range of $740 million to $770 million. In addition to the mutations added to the label, Vertex is continuing discussions with the FDA concerning the approval for additional people who have mutations responsive to Kalydeco®, including one of five "splice" mutations. These five mutations were evaluated as part of the previously disclosed Phase 3 EXPAND study in which the Kalydeco® monotherapy arm met its primary efficacy endpoint while being generally well tolerated. More than 600 people ages 2 and older in the U.S. have one of these mutations.
  • • On February 5, 2016, Vertex Pharmaceuticals announced that it received a Complete Response Letter from the FDA for its supplemental New Drug Application (sNDA) for the use of Kalydeco® (ivacaftor) in people with cystic fibrosis ages 2 and older who have one of 23 residual function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The FDA determined that it cannot approve the application in its present form. Vertex plans to meet with the FDA to determine an appropriate path forward. The sNDA is based on preclinical data for ivacaftor in residual function mutations, the established clinical profile of Kalydeco® and on previously reported data from an exploratory Phase 2a study. In 19 of the 24 patients enrolled in this study, eight of the 23 mutations proposed in the sNDA were represented. Kalydeco®, which received the FDA's Breakthrough Therapy Designation in 2013, is currently approved in the U.S. to treat people with CF ages 2 and older who have one of 10 mutations in the CFTR gene (G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R or R117H). As with the mutations for which Kalydeco® is approved, this group of 23 residual function mutations is known to have some functional CFTR protein at the cell surface.  The 23 residual function mutations included in the sNDA are: 2789+5G- > A, 3849+10kbC- > T, 3272-26A- > G, 711+3A- > G, E56K, P67L, R74W, D110E, D110H, R117C, L206W, R347H, R352Q, A455E, D579G, E831X, S945L, S977F, F1052V, R1070W, F1074L, D1152H, and D1270N.
  • The submission was also based on observed in vitro increases in chloride transport in response to ivacaftor in cells expressing CFTR. The presence of CFTR protein at the cell surface and increases in chloride transport are characteristics associated with clinical response to Kalydeco®.
  • • On 24 September 2015, the Committee for Medicinal Products for Human Use (CHMP) adopted two positive opinions recommending changes to the terms of the marketing authorisation for Kalydeco®. For the currently available 150 mg film-coated tablets, the CHMP recommended extending the indication to include: “treatment of patients with cystic fibrosis (CF) aged 18 years and older who have an R117H mutation in the CFTR gene.” In addition, the CHMP recommended extending the marketing authorisation for Kalydeco® to include two new presentations: 50 mg and 75 mg granules in sachet. The granules are for use in children aged 2 years and older in the previously authorised indication. The full indication for Kalydeco tablets will be: “treatment of patients with cystic fibrosis (CF) aged 6 years and older and weighing 25 kg or more who have one of the following gating (class III) mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R, “treatment of patients with cystic fibrosis (CF) aged 18 years and older who have an R117H mutation in the CFTR gene.”
  • The full indication for Kalydeco granules will be: “treatment of children with cystic fibrosis (CF) aged 2 years and older and weighing less than 25 kg who have one of the following gating (class III) mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R (see sections 4.4 and 5.1).”
  • • On March 18, 2015, Vertex Pharmaceuticals announced that the FDA approved Kalydeco® for use in children ages 2 to 5 with cystic fibrosis (CF) who have one of 10 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R and R117H). Prior to today's approval, Kalydeco® was approved in the United States for people ages 6 and older with these mutations. There are approximately 300 children in the United States ages 2 to 5 who have one of these 10 mutations, including 150 who have the R117H mutation and 150 who have one of the other nine mutations that result in a gating defect in the CFTR protein. A new weight-based oral granule formulation of Kalydeco® (50 mg and 75 mg) that can be mixed in soft foods or liquids was created to meet the needs of children in this age group who may be unable to swallow a tablet.
  • The approval is based on previously announced results of an open-label Phase 3 24-week study that was designed to evaluate the safety and pharmacokinetics of weight-based dosing of ivacaftor (50 mg or 75 mg twice daily) in children ages 2 to 5. With this approval, more than 3,400 people are currently eligible for treatment with Kalydeco® in the United States , Canada , Europe and Australia . In Europe , an MAA line extension for ivacaftor in children ages 2 to 5 with specific mutations in the CFTR gene has been validated by the European Medicines Agency (EMA) and is currently under review by the Committee for Medicinal Products for Human Use (CHMP).
  • * On December 29, 2014, Vertex Pharmaceuticals announced that the FDA approved a supplemental new drug application (sNDA) for the use of Kalydeco® (ivacaftor) in people with cystic fibrosis (CF) ages 6 and older who have the R117H mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Kalydeco® is now approved for use in the U.S. in people ages 6 and older with CF with one of the following ten mutations: R117H, G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P or G1349D. The approval is based on previously announced data from a Phase 3 study of ivacaftor that enrolled 69 people with CF ages 6 and older who had the R117H mutation.
  • • On October 21, 2014, Vertex Pharmaceuticals announced that the FDA's Pulmonary Allergy Drugs Advisory Committee (PADAC) voted 13-2 to recommend approval of Kalydeco® (ivacaftor) in people with cystic fibrosis (CF) ages 6 and older who have the R117H mutation in the cystic fibrosis transmembrane regulatory (CFTR) gene, which is the indication being reviewed by the FDA. The FDA is expected to make a decision on the approval of ivacaftor by December 30, 2014 under the Prescription Drug User Fee Act (PDUFA).
  • • On July 31, 2014, Vertex Pharmaceuticals announced that the European Commission has approved Kalydeco™ (ivacaftor) for people with cystic fibrosis (CF) ages 6 and older who have one of eight non-G551D gating mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The eight additional gating mutations included in this approval are: G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P and G1349D. In Europe , approximately 250 people ages 6 and older have one of these non-G551D gating mutations. This approval is based on previously announced data from the first part of a Phase 3, two-part, randomised, double-blind, placebo-controlled, cross-over study of 39 people with CF ages 6 and older who have a non-G551D gating mutation. The first part of the study showed statistically significant improvements in lung function (FEV1), sweat chloride, body mass index and CFQ-R scores. Data from the second part of the study were presented at the European Cystic Fibrosis Society Conference in June 2014 and showed that these improvements were maintained through 24 weeks of treatment. The safety profile was similar to prior Phase 3 studies of Kalydeco™ in people with the G551D mutation. In addition, the CHMP approved the inclusion of data from the long-term follow-up PERSIST study in the Kalydeco™ label. PERSIST is a Phase 3, open-label, 96-week, rollover extension trial that evaluated the long-term safety and durability of treatment with Kalydeco™ by enrolling people ages 6 and older with at least one copy of the G551D mutation who completed 48 weeks of treatment in the Phase 3 ENVISION and STRIVE studies (placebo and Kalydeco™ treatment groups) and met other eligibility criteria. Results from PERSIST demonstrated that the safety and efficacy of Kalydeco™ seen in the Phase 3 STRIVE and ENVISION trials was maintained through nearly three years (144 weeks) in G551D patients.
  • • On June 30, 2014, Vertex Pharmaceuticals announced the submission of a supplemental New Drug Application (sNDA) to the FDA for the approval of Kalydeco® in people with cystic fibrosis (CF) ages 18 and older who have the R117H mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In the United States , Kalydeco® is currently approved for use in people with CF ages 6 and older who have one of the following nine mutations: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P or G1349D. In the United States , approximately 300 people have the R117H mutation and are 18 years of age or older. R117H is the most common residual function mutation and also has a defect in the gating of the CFTR protein. In addition to the sNDA submission, Vertex intends to submit a Marketing Authorization Application (MAA) variation in Europe in the third quarter of 2014 for people with CF ages 18 and older who have the R117H mutation in the CFTR gene. The sNDA submission is based on previously announced data from a Phase 3 study of ivacaftor that enrolled 69 people with CF ages 6 and older who had at least one R117H mutation. The study did not meet its primary endpoint of the mean absolute change from baseline in ppFEV1 (percent predicted forced expiratory volume in one second) for ivacaftor compared to placebo (treatment difference) across all patients, however a pre-specified subset analysis in people who were 18 years of age and older showed statistically significant improvements in lung function (ppFEV1) and other key secondary endpoints. The subset analysis included 50 people with CF ages 18 and older who had a mean baseline absolute FEV1 of 65 percent predicted. In these patients, a statistically significant mean absolute treatment difference of 5.0 percentage points (p=0.01) in ppFEV1 was observed through 24 weeks of treatment, which corresponded to a mean relative treatment difference of 9.1 percent (p=0.008). Four weeks following the completion of treatment with ivacaftor, patients in this subset analysis showed a mean absolute within-group decrease of -3.1 percentage points (p=0.001) in ppFEV1. People who took part in this study were eligible to enroll in an open-label rollover study where all patients received ivacaftor after a washout period of at least three weeks. After the first 12 weeks of treatment in the rollover study, the mean absolute improvement from baseline in lung function for patients ages 18 and older (n=46) was 5.1 percentage points (p < 0.0001). Across the 24-week study and through 12 weeks of treatment in the rollover study, treatment with ivacaftor also resulted in decreases in sweat chloride and improvements in CFQ-R. Across all the patients, the safety and tolerability results observed in the 24-week study and rollover study were consistent with those observed in prior Phase 3 studies of ivacaftor in people with CF. In the 24-week study, the most commonly observed adverse events in those who received ivacaftor were infective pulmonary exacerbation, cough and headache, which occurred with similar frequency compared to those who received placebo. Serious adverse events occurred in 17 percent of patients who received placebo versus 12 percent of patients who received ivacaftor. In the rollover study, the most common serious adverse event was infective pulmonary exacerbations.
  • • On 26 June 2014, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a variation to the terms of the marketing authorisation for Kalydeco®.The CHMP adopted a change to the indication of Kalydeco®, introducing new cystic fibrosis genotypes for which the use of Kalydeco is indicated. The full indication for Kalydeco will be as follows: Treatment of cystic fibrosis in patients age 6 years and older who have one of the following gating (class III) mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R.
  • • On June 16, 2014, Vertex Pharmaceuticals announced that it has signed a letter of intent with the pan- Canadian Pricing Alliance (pCPA) to enable the public reimbursement of Kalydeco® (ivacaftor) for the treatment of eligible Canadians with cystic fibrosis ages 6 and older who have the G551D mutation. The letter of intent represents an agreement in principle with the pCPA regarding the public reimbursement of Kalydeco® in Canada. However, before patients can get access through public reimbursement, each participating province or territory must decide to reimburse Kalydeco® through its individual drug program. In Canada , there are approximately 100 people ages 6 and older with this specific mutation. The process to add Kalydeco® to drug programs at the provincial and territorial level is ongoing. The letter of intent does not include the province of Quebec , which does not participate in the pCPA process. Kalydeco® is now available to eligible people with CF in more than 15 countries around the world, including the United States , England , Scotland , Northern Ireland , Wales , the Republic of Ireland , France , Germany , the Netherlands , Austria , Denmark , Sweden , Norway , Greece , Italy and Switzerland .
  • • On February 21, 2014, Vertex Pharmaceuticals has announced the FDA approved a supplemental New Drug Application (sNDA) for Kalydeco® for people with cystic fibrosis (CF) ages 6 and older who have one of eight additional mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Kalydeco® was first approved in January 2012 for people with CF ages 6 and older who have at least one copy of the G551D mutation. With the approval of the sNDA, Kalydeco® is now approved for use in people with CF with the following nine mutations: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P and G1349D. In the United States , approximately 150 people ages 6 and older have one of the additional eight mutations for which Kalydeco® is now approved. Kalydeco® was granted Breakthrough Therapy designation by the FDA in late 2012. The sNDA approval is based on previously announced data from a Phase 3, two-part, randomized, double-blind, placebo-controlled, cross-over study of 39 people with CF who had one of the following mutations: G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D or G970R. The study showed statistically significant improvements in lung function (FEV1) for people in the overall study population who received ivacaftor, and the safety profile was similar to prior Phase 3 studies in people with the G551D mutation. Based on data from four patients with the G970R mutation enrolled in the study, the efficacy of Kalydeco® in patients with the G970R mutation could not be established to support approval in the U.S. Vertex estimates that approximately 10 people with CF have the G970R mutation worldwide, including two people in the United States . Data from the study noted above were also used to support regulatory submissions in Europe , Canada and Australia for approval of Kalydeco® in additional people with CF ages 6 and older. In Europe and Australia , approximately 250 people with CF have these additional mutations.
  • • On September 30, 2013, Vertex Pharmaceuticals has announced the submission of a supplemental New Drug Application (sNDA) to the FDA for the approval of Kalydeco® (ivacaftor) monotherapy for people with cystic fibrosis ages 6 and older who have at least one non-G551D gating mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Kalydeco® is currently approved for people with CF ages 6 and older who have at least one copy of the G551D mutation. CF is caused by a defective CFTR protein that results from mutations in the CFTR gene. G551D is known as a gating mutation, and there are an additional nine known gating mutations. Gating mutations prevent the CFTR protein from opening or working (gating) properly at the cell surface. Worldwide, approximately 2,000 people with CF ages 6 and older have at least one copy of the G551D mutation, and approximately 400 people with CF ages 6 and older have at least one non-G551D gating mutation. The sNDA submission is based on previously announced data from a Phase 3 study of ivacaftor monotherapy that showed statistically significant improvements in lung function (FEV1). The mean absolute treatment difference in percent predicted FEV1 between treatment with ivacaftor and placebo was 10.7% (p < 0.0001) and the mean relative treatment difference in percent predicted FEV1 was 14.2% (p < 0.0001) through the 8-week treatment period. The safety and tolerability results observed in this study were consistent with those observed in prior Phase 3 studies of ivacaftor monotherapy in people with CF who have the G551D mutation. The study in gating mutations is one of three ongoing Phase 3 label-expansion studies designed to evaluate whether additional people with CF may benefit from treatment with ivacaftor alone. In addition to the sNDA submission, Vertex intends to submit a Marketing Authorization Application (MAA) variation in Europe in October 2013 for people with CF ages 6 and older who have at least one non-G551D gating mutation.
  • • On February 1, 2013, Vertex Pharmaceuticals has announced that the Health Service Executive (HSE) in the Republic of Ireland will fund Kalydeco® (ivacaftor) for people ages 6 and older who have at least one copy of the G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This decision follows an assessment of the medicine by the National Centre for Pharmacoecomomics (NCPE), which acknowledged the benefits of ivacaftor, including significant improvement in lung function, increased body weight, improvement in quality of life and a 55 percent reduction in pulmonary exacerbations, or periods of worsening respiratory signs and symptoms that often require treatment with antibiotics and hospitalisation. Vertex is working to make ivacaftor available to eligible people in Ireland as quickly as possible.
  • • On December 19, 2012, Vertex Pharmaceuticals has announced that a decision has been made by the National Health Service (NHS) in England to fund Kalydeco® (ivacaftor) for people ages 6 and older who have at least one copy of the G551D mutation in the CFTR gene. This announcement concludes a comprehensive and robust clinical and economic evaluation of the medicine by the NHS in England. Vertex has agreed to a patient access scheme with the NHS, the details of which remain confidential. Vertex will make ivacaftor available to eligible people with CF as quickly as possible and anticipates reimbursement to begin in the second quarter of 2013.
  • • On July 27, 2012, Vertex has announced it has received European Approval for Kalydeco® (ivacaftor) for people with cystic fibrosis ages 6 and older who have at least one copy of the G551D mutation in the CFTR gene. Kalydeco® is the first medicine to target the underlying cause of the disease in these patients. In people with the G551D mutation, Kalydeco® helps the defective CFTR protein function more normally. The approval of Kalydeco® comes two months after the CHMP issued a positive opinion and is the first European approval for Vertex. The European Commission's decision is based on positive findings from two global Phase 3 studies in which Kalydeco® demonstrated significant and sustained improvements in breathing, weight gain and other measures of disease for people ages 6 and older with this specific genetic mutation, compared to placebo. In addition, people who took Kalydeco® were 55 percent less likely to have pulmonary exacerbations, or periods of worsening in the signs and symptoms of the disease that often require treatment with antibiotics and hospital visits, than those who received placebo. Fewer people in the Kalydeco® treatment groups discontinued treatment due to adverse events than in the placebo groups. The majority of the adverse events associated with Kalydeco® were mild to moderate. Adverse reactions very commonly observed in those taking Kalydeco® (less than 1/10) included headache; upper respiratory tract infection (common cold) including sore throat and nasal congestion; rash; diarrhoea; and abdominal pain (stomach ache). Two patients in the group receiving Kalydeco® reported a serious adverse reaction of abdominal pain.
  • • On May 25, 2012, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended Kalydeco® (ivacaftor) for the treatment of cystic fibrosis in patients age 6 years and older who have a G551D mutation in the CFTR gene.
  • • On January 31, 2012, FDA has approved Kalydeco® for people with cystic fibrosis (CF) ages 6 and older who have at least one copy of the G551D mutation in the CFTR gene. Kalydeco® was granted approval in approximately three months, making it one of the fastest FDA approvals ever and marking the second approval of a new medicine from Vertex in less than a year. Vertex will begin shipping it to pharmacies in the United States this week. The approval of Kalydeco® was based on data from two Phase 3 studies of people with CF who have at least one copy of the G551D mutation. Those who were treated with Kalydeco® experienced significant and sustained improvements in lung function as well as other disease measures, including weight gain and certain quality of life measurements, compared to those who received placebo. People who took Kalydeco® also experienced significantly fewer pulmonary exacerbations, which are periods of worsening in the signs and symptoms of the disease that often require treatment with antibiotics and hospital visits. Fewer people in the Kalydeco® treatment groups discontinued treatment due to adverse events than in the placebo groups. The majority of adverse events associated with Kalydeco® were mild to moderate. Adverse events commonly observed included headache, upper respiratory tract infection (common cold), stomach pain and diarrhea.

Patents:

Submission of marketing authorization application USA :

Submission of marketing authorization application UE: 2011-10

Withdrawal of marketing authorization application USA:

Withdrawal of marketing authorization application UE:

US authorization: 2012-01-31/2015-03-18/2017-05-17

UE authorization: 2012-07-25

Favourable opinion UE: 2012-05-25/2015-09-24/2018-07-26

Favourable opinion USA:

Orphan status USA: 2006-12-20

Orphan status UE: 2008-07-08

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

Is general: Yes