OFEV

What it is

OFEV is a soft capsule formulation containing nintedanib esilate, available in 100 mg and 150 mg strengths. Nintedanib is a tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptors (VEGFR), platelet-derived growth factor receptors (PDGFR), and fibroblast growth factor receptors (FGFR).

Approved indications

— Treatment in combination with docetaxel for patients with locally advanced, metastatic or recurrent non-small cell lung cancer (NSCLC) of adenocarcinoma tumour histology after failure of first line chemotherapy. — Treatment of Idiopathic Pulmonary Fibrosis (IPF). — Treatment of other chronic fibrosing Interstitial Lung Diseases (ILDs) with a progressive phenotype. — Slowing the rate of decline in pulmonary function in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD).

Dosing overview

OFEV capsules should be taken orally, preferably with food, swallowed whole with water, and should not be chewed.

Key safety warnings

**Gastrointestinal disorders.** Diarrhoea was the most frequently reported gastrointestinal event in clinical trials; the majority of patients had mild to moderate diarrhoea, though 6.3% of patients had diarrhoea of grade ≥ 3 in combination treatment with docetaxel compared to 3.6% treated with docetaxel alone. Diarrhoea should be treated at first signs with adequate hydration and anti-diarrhoeal medicinal products such as loperamide, and may require dose interruption, dose reduction or discontinuation of therapy. Diarrhoea and vomiting may lead to dehydration with or without electrolyte disturbances which may progress to renal function impairment; in the event of dehydration, administration of electrolytes and fluids is required. **Gastrointestinal perforation and ischaemic colitis.** Due to the mechanism of action, nintedanib patients might have an increased risk of gastrointestinal perforations and ischaemic colitis; cases of GI perforations and cases of ischaemic colitis, some of which were fatal, have been reported in the post-marketing period. Particular caution should be exercised when treating patients with previous abdominal surgery, previous history of peptic ulceration, diverticular disease or receiving concomitant corticosteroids or NSAIDs; OFEV should only be initiated at least 4 weeks after abdominal surgery. **Liver enzyme elevations.** Cases of drug-induced liver injury have been observed with nintedanib treatment, and in the post-marketing period, severe liver injury with fatal outcome has been reported. Liver related adverse events of grade ≥ 3 were reported in 15.3% of patients treated with the combination of OFEV and docetaxel compared to 1.8% of patients treated with docetaxel alone. Female and Asian patients have a higher risk of elevations in liver enzymes. **Neutropenia and sepsis (NSCLC).** A higher frequency of neutropenia of CTCAE grade > 3 was observed in patients treated with OFEV in combination with docetaxel as compared to treatment with docetaxel alone; subsequent complications such as sepsis or febrile neutropenia have been observed, with febrile neutropenia reported in 7.5% of patients in the combination arm compared to 4.5% with docetaxel alone, and fatal sepsis reported in 0.9% of patients treated with OFEV in combination with docetaxel.

Contraindications

OFEV is contraindicated in patients with known hypersensitivity to nintedanib, peanut or soya, or to any of the excipients. OFEV is contraindicated during pregnancy.

PBS listing

OFEV 100 mg and 150 mg soft capsules are registered on the ARTG, first listed 2015-09-01. The PBAC recommended listing of OFEV for Idiopathic Pulmonary Fibrosis in November 2016 under certain conditions with risk sharing measures, and recommended listing for Progressive Fibrosing Interstitial Lung Disease in September 2021.

Regulatory history

OFEV 100 mg and 150 mg soft capsules were first registered on the ARTG on 2015-09-01. In November 2014, the PBAC did not recommend nintedanib for Idiopathic Pulmonary Fibrosis due to uncertain clinical benefit and unacceptable cost-effectiveness. In November 2016, the PBAC recommended listing for IPF under certain conditions with risk sharing measures. On 23 December 2020, the TGA approved the extension of indications for OFEV for the treatment of other chronic fibrosing interstitial lung diseases with a progressive phenotype, based on sufficient evidence of efficacy and an acceptable safety profile demonstrated in clinical data. In September 2021, the PBAC recommended listing for Progressive Fibrosing Interstitial Lung Disease as an Early Resolution Resubmission change to PBS listing.