• CF Drugs Update: January 2019

    Orkambi, Kalydeco and Smykevi: More Good News


    Cystic Fibrosis Ireland welcomes the news that Orkambi has been approved by the EMA (European Medicines Agency) for children aged 2-5 years old with 2 copies of the F508del gene alteration. 

    Orkambi was originally approved for reimbursement in Ireland for 12 years and older in 2017. Orkambi was subsequently extended to 6-11 year olds in 2018. The further extension of Orkambi to 2-5 years olds approved by the EMA is consistent with the drugs portfolio deal agreed in April 2017 between the HSE and Vertex Pharmaceuticals. 

    CFI will seek clarification from the HSE on timing of availability of the latest Orkambi extension in Ireland. 


    CF Ireland understands that the introduction of Symkevi (approved on 1 January 2019) is going very well. A small number of patients have been switched to Symkevi who were originally on Orkambi, based on clinical criteria and expert advice from Consultants. However CFI also understands that the vast majority of those on Orkambi will remain on Orkambi as CFI predicted in earlier news updates.

    Symkevi is a CFTR medication that is a possible alternate for those eligible for Orkambi and also for a small number of other linked gene alterations


    The EMA have also recently approved the extension of Kalydeco to 1-2 year olds. 

    Cystic Fibrosis Ireland is also seeking clarification if Kalydeco will be extended to those under 18 years of age with the R117H gene alteration. 

    Kalydeco was the first CFTR drug introduced to Ireland in 2013 of which Orkambi and Symkevi have since followed (2017 and 2019). These are the first drugs that treat the underlying cause of CF. They are personalised drugs in the sense that they are tailored for those with certain gene alterations.

    Kalydeco impacts on those with the G551D gene alteration (15% of the CF population in Ireland) but also other named gene alterations including R117H (6% of the CF population in Ireland). The most common gene alteration in Ireland and worldwide is people with CF with 2 copies of the F508del gene alteration (about 57% in Ireland). This is the group of patients eligible for Orkambi and Symkevi

  • CFI welcomes Government approval of new CF drug Symkevi

    Cystic Fibrosis Ireland welcomes Irish Government approval of a new Cystic Fibrosis drug Symkevi. This is the third in a series of groundbreaking and innovative drugs for CF in Ireland. These are precision CFTR drugs that treat the underlying cause of CF and are aimed at particular CF gene mutations- hence the need for more than one drug. 

    Symkevi is designed for those with the most common CF gene mutation in Ireland and worldwide, which is people with 2 copies of the F508del mutation (57% of the CF population in Ireland).

    Symkevi is also aimed at those with 1 copy of the F508del mutation and one of 14 mutations.

    The other 2 CFTR drugs that were previously approved by the Irish Government are Kalydeco (2013) and Orkambi (2017). The innovative deal struck in 2017 between Vertex and the HSE provided for both Orkambi but also known drugs that were 'in the pipeline' (i.e. undergoing very positive clinical trials, such as Symkevi). Similar deals using this pipeline approach have since been struck with the Netherlands and Sweden.

    The EMA approved Symkevi in November 2018, the Irish Government approved Symkevi today (20 December) and CFI expects this important to be available to patients in January 2019

    Philip Watt, CEO of CFI stated: '

    We thank again Ministers' Simon Harris TD and Finnian McGrath TD and An Taoiseach, Leo Varadkar TD with the support of all political parties for ensuring new and groundbreaking drugs are provided to patients with CF in Ireland without delay. 

    CFI also wishes to express our support to other patients with rare disease seeking access to drugs such as Alpha 1 and Duchene Muscular Dystrophy and we welcome the recently announced extension of Pembro to Women with Cervical cancer in Ireland'.


    Very encouraging Late Stage Study Results for forthcoming CF Triple-Combination drugs

    On 27 November Vertex pharmaceuticals released the initial Phase 3 clinical trial data for one of two next-generation, triple-combination drugs that are undergoing late stage clinical trials (Phase 3 trials). These are further part of the CFTR family of drugs that includes Klaydeco; Orkambi and most recently Symkevi.

    ‘The results are very encouraging’  said Philip Watt, CEO Cystic Fibrosis Ireland (CFI). 'They are still at clinical trial stage but they point to the increasingly strong possibility of further drugs coming down the line for those already on a CFTR drug and for some of those that are not. It continues to be a time of hope for people with CF. We are determined to try and ensure that no one gets left behind and that there will be a CFTR drug available to as many patients as possible in Ireland’

    In further, unconnected news - Novartis has sold TOBI Solution and Tobi Pod inhaler to US pharma firm, Mylan which also has a significant presence in Ireland (see information at end of this article).

    The results
    Positive results were announced from late-stage studies of a potential triple-combination CFTR drug for people with cystic fibrosis. Vertex Pharmaceuticals released Phase 3 clinical trial data for two studies of the next-generation modulator VX-659 in combination with ivacaftor and tezacaftor. 

    The first study tested this triple-combination drug on people with CF ages 12 years and older who have one copy of the most common gene alteration (mutation), F508del, and one minimal function mutation

    Results showed that those who received VX-659 combined with ivacaftor and tezacaftor had a 14 percent increase in lung function compared to participants taking a placebo. Researchers believe that anyone with at least one copy of the F508del mutation -- regardless of their second mutation -- could benefit from next-generation modulators.

    The second study included people with CF ages 12 years and older who have two copies of the F508del mutation. The trial compared the effectiveness of Symkevi (tezacaftor/ivacaftor) to VX-659 combined with tezacaftor and ivacaftor. Participants who were given VX-659 combined with tezacaftor and ivacaftor had a 10 percent improvement in lung function over those who were only given Symkevi® (tezacaftor/ivacaftor).

    Just as important are the wider impacts that these drugs will likely have including overall quality of life and reduction in exacerbations and weight gain. It’s too early to be definitive but the signs at this stage are very encouraging.

    Vertex will decide which of the two next-generation drugs they will submit to the U.S. Food and Drug Administration (FDA) for potential approval as a new drug. If approved, it is estimated that triple-combination CFTR modulators could potentially bring the benefits of therapies that treat the underlying cause of the disease to more than 90 percent of people with CF.

    Michael P. Boyle, M.D., senior vice president of therapeutics in the US Cystic Fibrosis Foundation stated:

    ‘It is an exciting time for the CF community, as we approach a milestone that seemed impossible even just a few years ago. Today's announcement represents an important step in our journey to developing treatments for the underlying cause of this disease for all people with cystic fibrosis. We are enthusiastic about the clinical benefit VX-659 demonstrated in these studies and look forward to seeing how these compare to the other next-generation modulator in clinical trials, VX-445.’

    CF Hospital Centres in Ireland have played a key role in supporting clinical trials for these medications. It is unclear yet when they will be submitted for approval to the FDA in the US and the EMA in Europe.

    There are presently 3 Vertex CFTR drugs approved for reimbursement in Ireland. These are ground-breaking drugs that treat the underlying cause of CF and include:

    Kalydeco (2013) primarily for those patients with the G551D gene alteration

    Orkambi (2017)for those patients with two copies of the F508del gene alteration

    Symkevi (2018) for those patients with two copies of the F508del gene alteration (alternate drug to Orkambi)

    In relation to Symkevi, CFI understands that a protocol is being developed. It is likely that those who are doing well on Orkambi (and the feedback to date is generally very positive) will remain on Orkambi.

    The impact of these drugs are closely monitored in Ireland. CFI will continue to provide impartial and informed information about these and future CF Drugs

    Further Drugs News: Novartis sells Tobramycin to Mylan
    In September 2018 Mylan, a Pennsylvania pharma company paid Novartis, the Swiss based pharm-company, 463 million dollars for its CF therapies including TOBI solution and TOBI pod-inhaler. This coincides with TOBI coming off patent. Nebulised Tobramycin was introduced in 1998 and has proven especially effective against Pseudomonos. Meanwhile Teva an international Pharma company has introduced a generic form of Nebulised Tobramycin.  These developments will likely result in significant price reductions in Nebulised Tobramycin to the HSE.