CF Drugs Update: July 2018
This is a brief summary of some recent developments in CF drug therapy availability (and likely future availability) in Ireland.
The roll out of Orkambi for 6-11 year olds in Ireland is going very well, including since extended use was approved in March 2018 (previously Orkambi was only licensed for 12 year olds and upwards).
CFI understands there has been an almost a 100% uptake in Orkambi among the 6-11 cohort of patients, representing over 110 patients. This is on top of the circa 380 patients aged 12 years and over already on Orkambi.
This means that the total CF population on Orkambi at present is 490 or about 37% of the CF population in Ireland. This represents a high proportion of those with two copies of the F508del gene alteration, especially since those aged 0-5 are presently excluded from Orkambi on age grounds. Further extensions of Orkambi are covered by the pipeline deal agreed between the HSE and Vertex in April 2017.
Plans are presently well advanced to further extend Orkambi to 2-5 year olds and this will likely be considered in the new year by the European Medicines Agency (EMA) and then by Ireland through a rapid review by the NCPE. It should be noted that this and other decisions may be delayed by the move of the EMA from London to the Netherlands as a result of Brexit.
To date, Orkambi has been approved in Germany; the Netherlands; Austria; Italy, France, Ireland and Sweden. England NHS turned it down in July 2018 for a second time, which will also impact on PWCF in N. Ireland who will continue to be denied this medication. Australia and Canada are likely to make a decision in the next couple of months. It should be noted that the Irish pipeline deal is reflected in the agreements with the Netherlands and Sweden.
Vertex have recently released promising results from studies into two drugs, a double combination therapy called Symdeko, and a triple combination therapy. The double combination therapy (Symdeko) uses a combination of ivacaftor and tezacaftor. The drug has been tested on people with CF with two copies of the F508del mutation and those with one copy of F508del and another mutation, and results have been positive.
The triple combination therapy uses a combination of ivacaftor, tezacaftor and one of three new compounds, and could work in people with one copy of the F508del mutation and one copy of a 'minimal function mutation' - approximately 90% of the CF population.
Symdeko was approved by the Food and Drug Administration (FDA) in the United States in February 2018 and may be approved by the EMA as early as February 2019. Under the pipeline deal this drug would be made available in Ireland after a rapid review by the NCPE. It is likely that some patients presently on Orkambi will be switched to Smydeko, but the criteria for switching is not yet clear.
VX 659 plus tezacaftor and ivcaftor and VX445 plus tezacaftor and ivcaftor
These two separate triple combination therapies are in phase 3 clinical trials at present following very promising results from phase 2. The target genotypes are or PWCF with one F508del and one minimal function gene alteration who don’t currently have a CFTR precision medicine – we estimate around 100-150 patients in Ireland may fall into this cohort- about 10% or more of the total CF population. These 2 therapies are presently outside the ‘pipeline deal’ but CFI will of course seek to have them included once the results of the Phase 3 trials become verified. Phase 2 trials showed a fantastic increase in FEV1 of 13 percentage points from baseline, which would put this drug therapy in the Kalydeco range of effectiveness for that marker, although it will also be important to use other markers to assess its full impact.
In short, CFI envisages that up to 90% of people with CF, and perhaps more, will be on one of the above ground-breaking CFTR drugs in the next few years. We predict that, all going to plan, this is going to bring a further major boost on both life expectancy and quality of life for people with CF in Ireland. Important as these new and innovative drugs are, CFI reminds our patients and families that they need to continue to adhere to the fully range of therapies, exercise and physiotherapy that has been prescribed for their care by their CF team. CFI thanks the CF centres in Ireland who have been involved in clinical trials and other research related to CFTR drug therapies, as we know this contribution has been important.
Anti-Biotics: New Colobreathe Capsule and Tymbrineb available in Ireland
There have also been some important recent developments in relation to anti-biotics for people with CF in Ireland.
Teva Pharmaceuticals Ireland have launched a new Colobreathe (colistimethate sodium) capsule which is now available in Ireland. This new capsule is designed ‘to help minimise capsule fracture on administration when used with the Turbospin inhaler’.
Teva Pharmaceuticals have also informed CFI they have launched a new generic medicine called Tymbrineb (tobramycin) nebuliser solution. Tymbrineb will be available in Ireland from 22 June 2018, and is indicated for the long-term management of chronic pulmonary infection due to Pseudomonas aeruginosa (in patients 6 years and older).
CFI understands that this generic form of tobramycin and is an outcome of the patent for tobramycin expiring in Ireland, thus bringing competition into the market for this important and widely used anti-biotic. CFI and for their continuing support of the CF annual medical and scientific meeting in Killarney over many years.
A note on Patents and Drug Therapies
CFI supports the responsible and planned use of generic medicines and biosimilars in Ireland to reduce the cost of drug therapies for all patients, including for those with CF. CFI has also campaigned with other patient groups on this issue (see references to further information below).
Patents for drug therapies in Ireland (and the EU) normally last 20 years. Once this period is over, other drug companies can enter into competition and bring in what is known as ‘generic drugs’ that are often at a fraction of a price of the original patent drug. The price of the original patented drug also falls after the end of the patent period.
In 2012 Ireland had the third highest per person spending on drugs of all 25 countries in the EU where data was available. Ireland was 43% above the average and Ireland’s increases have been among the highest, nearly tripling from 2000-2008 (Briody)
From an industry perspective, pharma contend that they often only get only 8-12 years on patent because it takes so long for drugs to be reimbursed. They also point out to job losses arising from the ‘cliff’ at the end of patent. International human rights groups such as Oxfam and Medicines Sans Frontiers have contended that there is need to reform the patent system to reduce the cost of drugs. Industry contends that they need strong incentives to invest in drug therapies, given the very high costs and risks associated with research and development. It should be noted the price of generics has declined in time relative to the price of the patented drugs. The discount was 35% in 2010 to about 50-60% in recent years in Ireland. This shows that drug prices can be reduced by more effective intervention by Government at a national policy level.
For more information visit
J. Briody. ‘How Drugs Prices are set in Ireland’ www.publicpolicy.ie http://www.publicpolicy.ie/wp-content/uploads/Pharmaceutical-Prices-in-Ireland-J-Briody-Draft-2.pdf
MRCG and IPPOSI. ‘Steering a course to avoid the drug iceberg’ (Two Reports) http://www.mrcg.ie/go/news/in_the_news/mrcg-ipposi-meeting-report-the-drug-iceberg