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


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.