Trikafta or Kaftrio

[Joseph260268]

Good evening everyone, can anyone tell me if Trikafta or Kaftrio is only available to certain people with CF? Is anyone not suffering from CF ever been prescribed it?

Thank you all in advance

Joe x

[Hidden]

Hi Joe. Trikafta - for some reason named Kaftrio in Europe - is only currently available on compassionate grounds in the UK to people with cf carrying the right genetic mutation(s) that cause the disease and whose health is deteriorating rapidly and/or they’re in need of a lung transplant. The European Medicines Agency (EMA) have in the last two weeks granted a licence for Kaftrio to be available to all patients in Europe with cf who have either two copies of F508del, which is the most common mutation involved in cf, or one copy of F508del and one of an as yet unreleased list of specific minimal function mutations, however it’s likely to be the autumn at the earliest before this translates to prescriptions being issued on the NHS. It’s actually caused a lot of upset because the original belief both amongst patients and professionals here was that it would be licensed the same way that it is in the US where everyone with at least one copy of F508del has been given access to it.

Vertex have this week submitted a licence extension request to the EMA, though, on the back of further phase 3 trials with people with F508del and certain gating and residual function mutations. If approved, this means that the license applicable in the UK will be on a much more similar footing to the FDA licence already in effect stateside and allow the majority of cf patients here to access Kaftrio, although aside from needing the right mutations, as with all the new precision meds from Vertex, there are currently contraindications for taking it where patients have significant liver disease. Overall, it’s thought there’ll probably be somewhere between 10 and 20% of UK cf patients who either aren’t eligible or can’t take it for some reason.

With regards to whether or not it’s available to those without cf, the short answer is no. These drugs are designed to correct the action of the faulty genes that cause cf, so only work where those mutations are present to begin with, and although more research is needed, at this point it’s believed to only work for certain cf mutations anyway. Unless it’s found in years to come that other lung conditions also have their root in mutations of the CFTR gene that cause cf, for instance non cf bronchiectasis, it’s unlikely to ever be used for other patient groups as it can’t correct something that isn’t present.

[Joseph260268 in reply to Hidden]

Thank you so much for your informative reply. I am currently on the lung transplant list awaiting a double transplant so it gives me something further to look into.

[Hidden in reply to Joseph260268]

Have you got cf, Joe?

[Joseph260268 in reply to Hidden]

Good morning, no I haven’t. I am currently listed for a double lung transplant, I suffer with severe bronchiectasis for 15 years and i am on 02 24/7 and a CPap mask at night as I am a C02 retainer. I have never smoked in my life and I am just trying to find out other options just in case my call for new lungs never comes up. x

[lucie982]

Cant say ive heard of anyone without CF using it, its a very specific drug to treat the underlying issues of having certain faulty cftr genes. If you knew you had one faulty gene and were under a consultant who was very suspicious of atypical CF and were really quite unwell there may be scope for compasionate use. Athough a deal has been made its not widely avaiable yet.

[Hidden in reply to lucie982]

My understanding is that only people with a clinically confirmed cf diagnosis - meaning two mutations and a positive sweat test - will have access, partly due to the cost implications. And even with atypical cf, the vast majority of people these days have two identified mutations. The only application of the drug at this stage is for the F508del mutation in combination with certain other mutations: as F508del is carried as at least one of the two required mutations by 90% of the cf population and by far the most prevalent in carriers by a mile in keeping with that, if the one gene you had was this gene, you’d know about it, and the absent second gene likely wouldn’t be covered for use except potentially under the caveat I mention below. If the only gene you know you have is not F508del, you’re not going to be eligible even you ultimately get a cf diagnosis, because outside of completely cocking up the first stage of the genetic screening to the point of clinical negligence, F508del is impossible to miss.

There is apparently meant to be some leeway with the licensing agreement in England (not the whole of the UK) as a result of the NICE negotiations with Vertex last year. No one’s quite sure what it will look like in reality yet, but the suggestion is that consultants may be able to prescribe Kaftrio at their discretion to people with a second mutation not covered by the EMA licensing agreement, but that does meet the FDA licensing terms, which in practice basically means as long as they have one copy of F508del. Any other use in cases where neither genotype is F508del will most likely be a long way off, if it ever happens, even on compassionate grounds, and likely depend on the future outcomes of the ongoing HIT-CF research. It’s a project trying to see if any of the existing modulators might work for the people like my daughter who are in the 10% that don’t carry even one copy of F508del and therefore won’t benefit from Kaftrio - or any of the other precision meds - as things stand.

[Joseph260268 in reply to Hidden]

Thank you once again.

[lucie982 in reply to Hidden]

yes the f508 gene would be a must unless under the circumstances you mention. They wont stop the search for that last 10% Hopefully some other treatments in the pipeline will help your daughter and others with more rare combinations. My son turned 12 last week and has 2 df508 mutations, Orkambi really didnt change anything for him, hes well but LF at lower end of normal and struggles with appetite, id love to see him eat more. Luckily no side effects from the Orkambi either. Hope your daughters keeping well

[Hidden in reply to lucie982]

Unfortunately, though, they could have started looking at the 10% when Ivacaftor was first licensed by the EMA in 2012, but for some reason didn’t do anything at all until 2018. The research in regards to the existing precision meds is 6 years behind where it should be, at best, and we personally don’t have a huge amount of leeway to play with: Bod doesn’t keep well, has never kept well, and at 12 has an absolute best fev1 of 75% but more usually lingers around the 70% mark. When she’s unwell, she routinely drops down into the 40s and 50s, and she’s permanently lost at least 6% in the last 18 months alone, although some of that may be because of the unbelievably poor tertiary care she was getting for the last couple of years. Out of desperation I moved us to get her under the Brompton last year, and a ct scan they did showed she has extensive lung damage including the start of bronchiectasis. She’s spent two years of her life so far in hospital having IVs. Thankfully weight gain isn’t a huge issue when well, although she quite routinely drops a couple of kilos whenever we go in for treatment.

Orkambi seems to have been quite hit and miss, tbh: there are figures out there that suggest about 30% of patients either can’t tolerate it or see no real benefit. You may have come across him online, but there’s a chap called Marc Cotterill who got Kaftrio on compassionate grounds earlier this year, and according to a mutual contact in the cf world, he went from needing a transplant to better fev1 than the child in about 4 months. The average improvement is around 14%, but in reality some people are actually getting improvements of up to 50 or 60%. Hopefully, Kaftrio will be really good for your son.

[Joseph260268 in reply to Hidden]

Thank you Charlie it’s actually for me I don’t have a son. x

[Hidden in reply to Joseph260268]

That was in reply to Lucie, Joe - her son has cf and is on orkambi and she asked about my daughter who is the same age and also has cf.

[Joseph260268 in reply to Hidden]

Sorry Charlie I didn’t realise you were addressing someone else. Thank you once again for all your helpful information.

[Joseph260268 in reply to lucie982]

Thank you Lucie. x

[cofdrop-UK in reply to lucie982]

A very warm welcome to you lucie and of course your son 🙂

Love cx

[Joseph260268 in reply to lucie982]

Thank you so much for your informative reply.

[cofdrop-UK]

Hi Joe,

I wasn’t happy with the way the media announced these new drugs as a breakthrough for cystic fibrosis, without explaining that it would be of benefit for a minority of patients with cf (hopefully enormous benefit - I do hope so). Clarification was definitely needed to avoid false hope.

With regard to non cf bronchiectasis, I expect it raised some hopes for some people with non cf BE with the way it was presented that it would ‘trickle down’, as most of our drugs have, without a full explanation of the facts. As you know it is only relatively recently that there has been any research specifically for non cf bronchiectasis. So neglected ncfbe has been in my 72 years as a bronchie that it is only the 4th world bronchie conference this year!!!

I wish you well Joe and stay safe.

Love cx

[Joseph260268 in reply to cofdrop-UK]

Thank you for your reply.