The approval enables a small number of people with cystic fibrosis in the U.S. who were not previously eligible for a CFTR modulator therapy to access a drug that treats the underlying cause of their disease for the first time.
The FDA based its decision on laboratory evidence submitted by Vertex Pharmaceuticals that demonstrates these CFTR mutations respond to Trikafta and on established safety and efficacy data for the drug.
Because only a small number of people with CF have these mutations, conducting a traditional clinical trial with hundreds of people is not practical. Testing how well these mutations respond to modulators in the lab — a process known as theratyping — enables people with rare CFTR mutations to gain access to already approved modulators quickly and safely.
Expanding approval to additional mutations and age groups allows greater access to Trikafta and other modulator therapies. Trikafta was first approved in 2019 for people with CF ages 12 and older with at least one copy of the F508del mutation. Since then, the modulator has been expanded to people with CF ages 2 and older who have at least one copy of 178 specified mutations. With today’s announcement, Trikafta is approved to treat the following additional mutations:
| 1507_1515del9 | 2183A→G | A1067P | A107G | A309D | A62P | C491R | D1445N |
| D565G | D993Y | E116Q | E292K | F1107L | F200I | F587I | G1047R |
| G1123R | G1247R | G27E | G424S | G480S | G551A | G970S | H620P |
| H620Q | H939R;H949L | I105N | I125T | I148N | I331N | I506L | I556V |
| K162E | K464E | L1011S | L137P | L333F | L333H | L441P | L619S |
| M1137V | M150K | N1088D | N1303I | N186K | N187K | N418S | P140S |
| P499A | P750L | Q1313K | Q372H | Q493R | Q552P | R1048G | R117C;G576A;R668C |
| R297Q | R31C | R516S | R555G | R709Q | R75L | S1045Y | S108F |
| S1118F | S1235R | S549I | T1086I | T1246I | T1299I | T351I | V392G |
| V603F | Y301C | 2789+5G→A | 3272-26A→G | 3849+10kbC→T | N1303K | 711+3A→G | E831X |
| 5T;TG12 | 5T;TG13 | 296+28A→G | 621+3A→G | 1898+3A→G | 2789+ 2insA | 3850-3T→G | 3600G→A |
| 3849+4A→G | 3849+40A→G | 4005+2T→C | 1341G→A | 3041-15T→G | 2752-26A→G |
New Safety Information
In addition, Vertex announced that safety information on liver injury and liver failure has been updated from warnings and precautions to a boxed warning. Please speak to your clinician with any questions or concerns.
How a Label Expansion Works
The Cystic Fibrosis Foundation recently published the results of its own testing to determine whether certain mutations that have not been approved for Trikafta would respond to the modulator. Although these results are informative, they could not be used to gain FDA approval for Trikafta to treat additional mutations.
To obtain today’s FDA approval of a label expansion, the drug’s manufacturer, Vertex, was required to conduct its own testing and submit its own data to the FDA for review. A label expansion is important because it allows people with CF with those mutations to seek insurance coverage for Trikafta (or other modulators).
For Certain Mutations Not Approved for Modulators
For those who live with a mutation that is not on Trikafta’s label, the Foundation encourages them to speak with their care team about nasal cell testing at Cincinnati’s Children’s Hospital Medical Center to determine whether their mutation would respond to Trikafta or another modulator. Individuals wishing to undergo testing should carry at least one CFTR mutation expected to make a full-length CFTR protein, because nonsense, frameshift, and many splice mutations will not respond to modulators.
Data derived from a successful test of nasal cells may be used to seek insurance coverage for an off-label prescription of Trikafta. We recommend that people with CF first contact Compass to see how much their insurance is likely to cover and what their co-pays would be for Trikafta.