Products

Date: 2017-07-13

Type of information: Product launch

Product name: Orkambi®

Compound: lumacaftor and ivacaftor

Therapeutic area: Rare diseases

Action mechanism:

• CFTR potentiator/cystic fibrosis transmembrane regulator (CFTR) protein modulator. Ivacaftor (Kalydeco®) is a CFTR (CF transmembrane conductance regulator protein) potentiator. Lumacaftor is an investigational CFTR corrector that partially restores CFTR function in people who are homozygous for F508del-CFTR. This gene encodes for the CFTR protein which is a chloride channel normally present at the surface of epithelial cells in multiple organs. Lumacaftor improves the cellular processing and trafficking of the F508del-CFTR protein to the cell membrane, while ivacaftor facilitates the function of the CFTR protein by increasing the CFTR channel gating. The combined effect of lumacaftor and ivacaftor results in increased quantity and function of F508del-CFTR protein at the cell surface, resulting in increased chloride ion transport.

Company: Vertex Pharmaceuticals (USA - MA)

Disease:

cystic fibrosis

Latest news:

• •  On July 13, 2017,  Vertex Pharmaceuticals announced that the Italian Medicines Agency (Agenzia Italiana del Farmaco , or AIFA) has agreed to reimburse Orkambi® (lumacaftor/ivacaftor) for the treatment of cystic fibrosis in people ages 12 and older who have two copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator gene. The agreement is published online in the Italian Official Gazette .  Recent European pricing and reimbursement agreements have enabled broad access to Orkambi® for thousands of eligible patients in Austria , Denmark , Germany , Ireland , Italy and Luxembourg. Negotiations continue in a number of other countries where CF is prevalent, including France and the United Kingdom
• • On June 9, 2017, Vertex Pharmaceuticals announced that the company has submitted a Marketing Authorization Application (MAA) line extension in March 2017 in the EU for the use of Orkambi® in children with cystic fibrosis ages 6 through 11 who have two copies of the F508del mutation.
• On June 1, 2017, Vertex Pharmaceuticals announced it has reached an agreement with the Health Service Executive (HSE) in the Republic of Ireland to fund Orkambi® (lumacaftor/ivacaftor) for all of the approximately 500 people in Ireland with cystic fibrosis ages 12 and older who have two copies of the F508del 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 December 19, 2016, Vertex Pharmaceuticals announced it has reached a pricing and reimbursement agreement for Orkambi® (lumacaftor/ivacaftor) with the German Federal Association of the Statutory Health Insurances (GKV-SV). This announcement follows a comprehensive benefit assessment of the medicine by the German Federal Joint Committee (G-BA), which recognized the "considerable additional benefit" of Orkambi® for people with cystic fibrosis who have two copies of the F508del mutation. Orkambi® has been available to eligible patients in Germany since it was granted marketing authorization from the European Commission in November 2015 , and the reimbursement agreement took effect on December 16, 2016 . In addition to Germany , Orkambi® is available to eligible people with cystic fibrosis in the United States , Austria , and France .
•  On September 28, 2016, Vertex Pharmaceuticals announced that the FDA approved Orkambi® (lumacaftor/ivacaftor) for use in children with cystic fibrosis ages 6 through 11 who have two copies of the F508del mutation. The drug was previously approved by the FDA for use in people ages 12 and older with two copies of the F508del mutation. With this new approval, approximately 11,000 people with cystic fibrosis are eligible for treatment with Orkambi® in the United States . The approval is based on data from a previously announced open-label Phase 3 clinical safety study of Orkambi® presented at the 39th European Cystic Fibrosis Society Conference in June 2016 . Vertex plans to submit a Marketing Authorization Application (MAA) variation in the European Union in the first half of 2017 for children ages 6 through 11 who have two copies of the F508del mutation. This application will be based on data from a Phase 3 efficacy study with a primary endpoint of absolute change in lung clearance index (LCI). These data are expected before the end of 2016.
• On May 31, 2016, Vertex Pharmaceuticals announced that the FDA has accepted for review a supplemental New Drug Application (sNDA) for the use of Orkambi® (lumacaftor/ivacaftor) in people with cystic fibrosis ages 6 to 11 who have two copies of the F508del mutation. The FDA granted Vertex's request for Priority Review of this sNDA, and a target review date of September 30, 2016 was set under the Prescription Drug User Fee Act (PDUFA). The sNDA is based on data from an open label Phase 3 clinical safety study of Orkambi®. To support potential approval in the European Union , a six-month Phase 3 efficacy study of children ages 6 to 11 is ongoing. Vertex recently completed enrollment in this study and, pending data from the study, plans to submit a Marketing Authorization Application variation in the European Union in the first half of 2017 for children ages 6 to 11 who have two copies of the F508del mutation. The primary endpoint of this efficacy study is the absolute change in lung clearance index (LCI). There are approximately 3,400 children ages 6 to 11 who have two copies of the F508del mutation in the European Union .
• On 24 September 2015, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Orkambi®, intended for the treatment of cystic fibrosis (CF). Orkambi® was designated as an orphan medicinal product on 22 August 2014. Orkambi® will be available as 200 mg/125 mg film-coated tablets. Orkambi® is to be used in patients with the specific F508del mutation affecting the CF transmembrane conductance regulator (CFTR) gene. The benefits of Orkambi® are its ability to improve pulmonary function [measured as the absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1)], increase the body weight and decrease the rate of pulmonary exacerbations in CF patients homozygous with F508del-CFTR. Mean improvement in ppFEV1, although of limited magnitude, was rapid in onset (15 days after starting treatment), sustained throughout the 48 week treatment period and observed regardless of age, disease severity, sex and geographic region. The most common side effects in patients aged 12 years and older who received lumacaftor/ivacaftor were dyspnoea, diarrhoea, and nausea. The full indication is: "Orkambi® is indicated for the treatment of cystic fibrosis (CF) in patients aged 12 years and older who are homozygous for the F508del mutation in the CFTR gene. It is proposed that Orkambi be prescribed by physicians experienced in the treatment of cystic fibrosis. If the patient’s genotype is unknown, an accurate and validated genotyping method should be performed to confirm the presence of the F508del mutation on both alleles of the CFTR gene.
• On July 2, 2015, the FDA approved the first drug for cystic fibrosis directed at treating the cause of the disease in people who have two copies of a specific mutation. Orkambi® (lumacaftor 200 mg/ivacaftor 125 mg) is now approved to treat cystic fibrosis in patients 12 years and older, who have the F508del mutation, which causes the production of an abnormal protein that disrupts how water and chloride are transported in the body. Orkambi® received FDA’s breakthrough therapy designation because the sponsor demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over available therapies. The FDA also reviewed Orkambi® under the priority review program. The approval of Orkambi® was based on data from two Phase 3 studies (TRAFFIC and TRANSPORT) that enrolled more than 1,100 people with CF ages 12 and older with two copies of the F508del mutation. Patients treated with Orkambi® experienced statistically significant improvements in lung function. Patients also experienced reductions in pulmonary exacerbations and improvements in body mass index (BMI). The most common adverse events included shortness of breath and/or chest tightness, upper respiratory tract infection (common cold) and gastrointestinal symptoms (including nausea, diarrhea, or gas).
• On November 5, 2014, Vertex Pharmaceuticals announced the submission of a New Drug Application to the FDA and a Marketing Authorization Application  to the European Medicines Agency  for a fully co-formulated combination of lumacaftor (400mg q12h) and ivacaftor (250mg q12h) for people with cystic fibrosis (CF) ages 12 and older who have two copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In the U.S., the combination of lumacaftor and ivacaftor received Breakthrough Therapy Designation in late 2012. The U.S. submission includes a request for Priority Review, which, if granted, would shorten the FDA's anticipated review time from approximately 12 to 8 months. The European Committee for Medicinal Products for Human Use has granted Vertex's request for Accelerated Assessment of the MAA, which is given to new medicines of major public health interest and shortens the review time from approximately 210 to 150 days for the CHMP to give an opinion following the start of the review. The CHMP opinion is then reviewed by the European Commission , which generally issues a final decision within three months. If approved, Vertex would then begin the country-by-country reimbursement approval process. Both applications seek approval for a fully co-formulated combination treatment dosed as two tablets every 12 hours (four tablets daily). The NDA and MAA submissions are based on previously announced data from two global Phase 3 studies, TRAFFIC and TRANSPORT, and the first interim data from the subsequent rollover study in people ages 12 and older who have two copies of the F508del mutation treated with standard-of-care medicines. The TRAFFIC and TRANSPORT studies showed improvements in lung function and other measures of disease, such as pulmonary exacerbations, through 24 weeks of treatment with lumacaftor in combination with ivacaftor. Initial interim data from the rollover study showed that lung function improvements were sustained for 48 total weeks of treatment (24 weeks in TRAFFIC/TRANSPORT + 24 weeks in rollover study). The combination was generally well tolerated in all three studies. In TRAFFIC and TRANSPORT, the most common adverse events were infective pulmonary exacerbation, cough, headache and increased sputum. In recognition of the immediate needs of some people with CF, Vertex is working to make the combination of lumacaftor and ivacaftor available to people ages 12 and older who have two copies of the F508del mutation, are in critical medical need and meet additional eligibility criteria. In the U.S., Vertex plans to begin a Phase 3b study for a limited number of people who have severe lung disease in the first quarter of 2015, followed by an expanded access program in the second quarter of the year, pending discussions with the FDA . Vertex will also work with regulatory authorities outside the United States toward implementing additional expanded access programs in other countries, with a goal of opening programs for eligible patients in the second quarter of 2015.
• On 8-10 July 2014, the Committee for Orphan Medicinal Products (COMP) has adopted a positive opinion recommending the approval of the orphan medicinal product designation for lumacaftor and ivacaftor fixed-dose combination for treatment of cystic fibrosis.
• On June 30, 2014, the FDA has granted the orphan drug status to lumacaftor and ivacaftor for treatment of cystic fibrosis.

Patents:

Submission of marketing authorization application USA : 2014-11-05

Submission of marketing authorization application UE: 2014-11-05/2017-03-01

Withdrawal of marketing authorization application USA:

Withdrawal of marketing authorization application UE:

US authorization: 2015-07-02/2016-09-28

UE authorization: 2015-11-19

Favourable opinion UE: 2015-09-24

Favourable opinion USA:

Orphan status USA: 2014-06-30

Orphan status UE: 2014-08-22

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

Is general: Yes