Appeal type: Medical necessity
Decision: Overturned

Diagnosis: cystic fibrosis (homozygous Delta F508)

Treatment: Trikafta 

The insurer denied coverage for Trikafta. The denial was reversed.

This patient is a male child with a past medical history notable for cystic fibrosis (homozygous Delta F508), multiple pulmonary exacerbations, pancreatic exocrine insufficiency, cystic fibrosis related liver disease, cirrhosis, esophageal varices, corrected heart disease (R anomalous coronary artery/ Patent Foramen Ovale (PFO) closure), rupture appendix, bowel obstruction/pseudo obstruction, obstructive sleep apnea and nasal polyps.  His treating teams (pulmonary, gastroenterology and transplant hepatology) have endorsed the use of Trikafta to address his multiple cystic fibrosis manifestations.

This patient has multi-system dysfunction related to his underlying cystic fibrosis.  Besides the usual pulmonary exacerbations and colonization with resistant organisms this patient has advanced cystic fibrosis related liver disease leading to cirrhosis and decompensated portal hypertension.  In regard to the use of Trikafta according to a review of the use of cystic fibrosis modulators from UpToDate the authors conclude the following:

We recommend treatment with a CFTR modulator for most individuals with CF who are greater than or equal to 12 years old and have responsive CFTR mutations.  The indications and efficacy of these drugs depend upon the CFTR mutations in the individual patient.  Therefore, all CF patients should undergo CFTR genotyping to determine if they carry a mutation that makes them eligible for CFTR modulator therapy.

In clinical trials involving patients with a wide range of CF genotypes, CFTR modulators have been shown to improve forced expiratory volume in one second (FEV1) and symptom-related quality of life (QoL) and reduce acute exacerbations.

Age greater than or equal to 12 years - For patients who have two F508del mutations (homozygotes) and are greater than or equal to 12 years old, we suggest triple therapy (elexacaftor-tezacaftor-ivacaftor) rather than dual therapy (tezacaftor-ivacaftor or lumacaftor-ivacaftor).

Both triple and dual therapies have demonstrated efficacy in this population, but in a four-week clinical trial, triple therapy achieved much greater improvements in FEV1 and symptom-related QoL compared with tezacaftor-ivacaftor.  Monotherapy with ivacaftor is not effective in this population, given its mechanism of action; however, it boosts the efficacy of the other corrector agents (lumacaftor, tezacaftor, and elexacaftor) when given in combination. Elexacaftor was identified by the same high-throughput screening strategy that identified other CFTR modulators.  Elexacaftor, in combination with tezacaftor-ivacaftor, increased the level of chloride transport in human bronchial epithelial cells heterozygote for F508del to approximately 50 percent of normal and even higher in homozygous F508del cells.  A 50 percent correction is approximately the same level that was achieved by ivacaftor in cells expressing the gating mutation G551D.
Phase 3 studies of elexacaftor-tezacaftor-ivacaftor in CF patients homozygous or heterozygous for F508del were completed in 2019 and led to the triple drug's approval in the United States for patients greater than 12 years.

For this particular patient given his multisystem injury secondary to cystic fibrosis including the eventual need for liver transplantation in the future this new agent may stabilize his pulmonary condition and potentially improve his cystic fibrosis related liver disease.  The use of Trikafta is medically necessary for the treatment of this patient as supported by the literature.  The studies demonstrate superiority of Trikafta over the suggested formulary agents that are not equivalent.    

The health plan did not act reasonably with sound medical judgment in the best interest of the patient.

The carrier's denial of coverage for Trikafta is reversed.  The medical necessity is substantiated.