INITIATION CRITERIA
For the treatment of cystic fibrosis (CF) in patients who meet all of the following criteria:
- 2 years of age and older;
AND
- Patient has a confirmed diagnoses of CF through a validated test documenting one of the following mutational results in the cystic fibrosis transmembrane conductance regulator (CFTR) gene;
a. Has at least one F508del mutation
OR
b. Has at least one N1303K mutation
OR
c. Has at least one mutation in the CFTR gene that is responsive to Trikafta listed in Table 1 below;
AND
- Patient has been optimized on best supportive care for their CF prior to starting Trikafta; AND
- Prescribed by a clinical specialist affiliated with a Canadian cystic fibrosis centre.
The following measurements must be completed prior to initiating treatment with Trikafta and will serve as the “baseline” measures upon which renewal of funding will be compared.
For patients 2 to less than 6 years of age:
- Number of days treated with oral and/or intravenous (IV) antibiotics for pulmonary exacerbations in the 6 months preceding* the request OR number of pulmonary exacerbations requiring oral and/or IV antibiotics in the 6 months preceding* the request;
AND
- Number of CF-related hospitalizations in the 6 months preceding* the request (if patient has not required any hospitalizations, no hospitalizations can be stated on the request);
AND
- Weight, height, and body mass index (BMI) and/or BMI z-score
For patients 6 years of and older:
- Baseline spirometry measurements of forced expiratory volume in 1 second (FEV1) in litres and percent predicted (ppFEV1) taken within the 3 months preceding* the request;
AND
- Either the number of days treated with oral and/or intravenous (IV) antibiotics for pulmonary exacerbations in the 6 months preceding* the request OR the number of pulmonary exacerbations requiring oral and/or IV antibiotics in the 6 months preceding the request;
AND
- Number of CF-related hospitalizations in the 6 months preceding* the request;
AND
- Weight, height, and body mass index (BMI) or BMI z-score in children;
AND
- A score from an age-appropriate Cystic Fibrosis Questionnaire as follows:
i) Cystic Fibrosis Questionnaire Child (CFQ-C) and Cystic Fibrosis Questionnaire-Parent (CFQ-P) if the patient is 6 to 13 years of age inclusive;
OR
ii) Cystic Fibrosis Questionnaire Revised (CFQ-R teen/adult) Respiratory Domain score it the patient is 14 years of age or older.
*Note that where it states “preceding the request”, this is intended to refer to the baseline measure taken before the initiation of Trikafta at the time the request is first submitted for funding consideration.
Notes:
- Pediatric patients who start therapy when they are 5 years of age or younger can provide the additional measures below at the time of renewal after turning 6 years old;
i) Baseline spirometry measurements of forced expiratory volume in 1 second (FEV1) in litres and percent predicted (ppFEV1)
ii) CFQ questionnaires at the time of renewal of funding when they become 6 years old.
- Case-by-case consideration will be provided for patients with mutations not listed in Table 1 below but where the mutation has been listed on the Health Canada product monograph for Trikafta or as supported by submitted in-vitro or in-vivo evidence aligned with the national review by Canada’s Drug Agency.
Exclusion criteria:
(Patients meeting any of the following will not be funded)
- Patient has undergone lung transplantation;
- Patient is using Trikafta as combination therapy with another cystic fibrosis transmembrane conductance regulator (CFTR) modulator.
Initial approval duration for 2 to 5 years (i.e., Less than 6 years old): 1 year
Initial approval duration for 6 years and older: 7 months
RENEWAL CRITERIA
Initial Renewal Criteria:
2 to 5 years:
Renewal of funding for patients 2 to 5 years of age will be considered in patients who are 2 to less than 6 years of age at the time the request is submitted where the prescriber confirms that the patient meets the following criteria:
- The patient continues to demonstrate continuing benefit from treatment with Trikafta;
AND
- The patient has demonstrated at least ONE of the following within six months of the renewal request:
i) A decrease in the total number of days on which the patient received treatment with oral and/or IV antibiotics for pulmonary exacerbations OR a decrease in the total number of pulmonary exacerbations requiring oral and/or IV antibiotics compared to the baseline measure
ii) A decreased number of cystic fibrosis related hospitalizations
iii) No decline in BMI using an age-appropriate measure compared with the baseline BMI measurement (i.e., BMI z-score)
6 years and older:
Renewal of funding for patients 6 years of age and older will be considered in patients demonstrating at least ONE of the following improvements after 6 months of treatment with Trikafta;
- In those providing a baseline lung function test, improvement of percent predicted FEV1 by 5% or more above the baseline measurement or improvement above the baseline of the associated age-appropriate lung function test used by the CF clinic to evaluate a pediatric patient;
- A decrease in the total number of days for which the patient received treatment with oral and/or IV antibiotics for pulmonary exacerbations compared with the 6-month period prior to initiating treatment OR a decrease in the total number of pulmonary exacerbations requiring oral and/or IV antibiotics compared with the 6-month period prior to initiating treatment;
- A decreased number of CF-related hospitalizations compared to the 6-month period prior to initiating Trikafta;
- No decline in BMI using an age-appropriate measure compared with the baseline BMI measurement;
- If the patient is 6 to 13 years of age inclusive, an improved or sustained quality of life through the scores of the age-appropriate questionnaires using the CFQ-C and CFQ-P compared to the baseline, scores using these questionnaires;
- If the patient is 14 years of age or older, an improvement by 4 points or more in the CFQ-R Respiratory Domain scale compared to baseline scores.
Subsequent renewal criteria:
For patients who have met the initiation criteria and initial renewal criteria.
- Ongoing renewal of funding will be provided for those who are continuing to benefit from therapy with Trikafta and who do not meet any of the exclusion criteria.
- At the time of renewal of funding, include the patient’s most recent ppFEV1 if the patient is 6 years of age or older and also include a clinical update to confirm the treatment benefits or response to trikafta that has been experienced by the patient.
Exclusion criteria for Initial and Renewal criteria:
(Patients meeting any of the following will not be funded)
- Patient has undergone lung transplantation;
- Patient is using Trikafta as combination therapy with another cystic fibrosis transmembrane conductance regulator (CFTR) modulator.
Approval Duration of first and subsequent renewals: 1 year
Table 1: Additional CFTR Mutations
CFTR mutations with significant clinical evidence of efficacy for trikafta, independent of the mutation on the second allele, are bolded and highlighted
*Complex/compound mutations where a single allele of the CFTR gene has multiple mutations; these exist independent of the presence of mutations on the other allele.
† CFTR mutations for which an in vitro response was also demonstrated for ivacaftor alone |
| 3141del9 |
E588V |
H139R |
P574H |
S341P |
| 546insCTA |
E822K† |
H199Y |
Q98R |
S364P |
| 711+3A→G† |
F191V |
H1054D |
Q237E† |
S492F |
| 2789+5G→A† |
F311del† |
H1085P |
Q237H† |
S549N† |
| 3272-26A→G† |
F311L† |
H1085R |
Q359R† |
S549R† |
| 3849+10kbC→T† |
F508C; S1251N *† |
H1375P† |
Q1291R† |
S737F† |
| A46D |
F508del |
I336K |
R74Q |
S912L |
| A120T† |
F575Y |
I502T |
R74W† |
S945L† |
| A234D† |
F1016S |
I601F |
R74W;D1270N |
S977F† |
| A349V† |
F1052V† |
I618T |
R74W;V201M * |
S1159F† |
| A455E |
F1074L† |
I980K |
R74W;V201M; |
S1159P† |
| A554E |
F1099L |
I1269N |
R117C† |
S1251N† |
| A1006E |
G27R |
I1366N |
R117G† |
S1255P† |
| A1067T† |
G85E |
L15P |
R117H† |
T338I† |
| D110E† |
G126D |
L165S |
R117L† |
T1036N |
| D110H† |
G178R† |
L206W |
R117P† |
V201M |
| D192G† |
G194R† |
L346P |
R258G |
V232D† |
| D443Y |
G194V |
L453S |
R334L |
V456A |
| D443Y;G576A; |
G314E† |
L967S† |
R334Q |
V456F |
| D579G† |
G463V |
L1077P |
R347H† |
V1153E |
| D614G |
G480C |
L1324P |
R347L† |
V1240G |
| D924N† |
G551D† |
L1335P |
R347P |
W361R |
| D979V |
G551S† |
L1480P† |
R352Q† |
W1098C |
| D1152H† |
G622D |
M265R |
R352W |
W1282R† |
| D1270N† |
G628R |
M952I† |
R933G† |
Y109N |
| E56K |
G970D† |
M952T† |
R1066H |
Y161D |
| E60K |
G1061R |
M1101K |
R1070Q† |
Y161S |
| E92K |
G1069R† |
N1303K |
R1070W† |
Y563N |
| E116K |
G1244E† |
P5L |
R1283M† |
Y1032C† |
| E193K† |
G1249R† |
P67L |
R1283S |
|
| E474K |
G1349D† |
P205S |
S13F |
|
Approved doses fo Trikafta:
(Refer to the product monograph for dose adjustments when used concomitantly with CYP3A inhibitors.)
Patients 2 to less than 6 years weighing less than 14 kg:
One packet (containing elexacaftor 80 mg, tezacaftor 40 mg and ivacaftor 60 mg granules) in the morning and one packet (ivacaftor 59.5 mg granules) in the evening.
Patients 2 to less than 6 years weighing 14 kg or more:
One packet (containing elexacaftor 100 mg, tezacaftor 50 mg and ivacaftor 75 mg granules) in the morning and one packet (ivacaftor 75 mg granules) in the evening.
6 to less than 12 years of age (weighing less than 30 kg):
2 tablets (each containing elexacaftor 50mg/tezacaftor 25mg/ivacaftor 37.5mg) taken in the morning & one tablet (ivacaftor 75mg) taken in the evening approximately 12 hours apart.
6 to less than 12 years of age (weighing 30 kg or more) OR 12 years of age and older:
2 tablets (each containing elexacaftor 100mg/ tezacaftor 50mg/ ivacaftor 75mg) taken in the morning & one tablet (ivacaftor 150mg) taken in the evening approximately 12 hours apart.
EAP Drug Request Form:
Standard Form for EAP Drug Requests