Products

Date: 2015-01-19

Type of information: Granting of a Market Authorisation in the EU

Product name: Ofev™

Compound: nintedanib

Therapeutic area: Rare diseases

Action mechanism:

• tyrosine kinase inhibitor. Nintedanib is an orall small molecule tyrosine kinase inhibitor. This triple angiokinase inhibitor targets the three receptors crucially involved in angiogenesis and tumour growth: vascular endothelial growth factor receptors (VEGFR 1-3), platelet-derived growth factor receptors (PDGFR alpha and beta), and fibroblast growth factor receptors (FGFR 1-3).  All three receptors are crucially involved in the formation and maintenance of new blood vessels (angiogenesis); their blockade may lead to the inhibition of angiogenesis, which plays a critical role in tumour growth and spread.

Company: Boehringer Ingelheim (Germany)

Disease: idiopathic pulmonary fibrosis

Latest news:

• • On January 19, 2015, Boehringer Ingelheim announced that the European Commission (EC) has approved Ofev® (nintedanib) for the treatment of idiopathic pulmonary fibrosis (IPF), following an expedited review and positive CHMP opinion on 20 November 2014.
• The approval is based on results from the replicate INPULSIS, involving 1,066 patients from 24 countries. INPULSIS® results showed that nintedanib* slowed disease progression by reducing the annual rate of decline in lung function by 50% in a broad range of IPF patient types including patients with early disease (forced vital capacity (FVC) >90% pred), limited radiographic fibrosis (no honeycombing) on high resolution computed tomography (HRCT) and those with emphysema. Nintedanib* has been shown to significantly reduce the risk of adjudicated acute exacerbations‡ by 68%.
• • On 20 November 2014, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Ofev®, 100 mg and 150 mg, soft capsules intended for adults in the treatment of idiopathic pulmonary fibrosis.
• The benefits with Ofev® are its ability to reduce the rate of deterioration of lung function measured as decline of absolute volume of Forced Vital Capacity in patients with idiopathic pulmonary fibrosis. It is noted that demonstration of this effect in the two pivotal clinical studies showed a clear and consistent benefit in reducing the decline of FVC by approximately 94 mL/year and 125 mL/year respectively. The most common side effects are: gastrointestinal disorders, diarrhoea, vomiting, nausea, alanine aminotransferase increase, aspartase aminotransferase increase. A pharmacovigilance plan for Ofev® will be implemented as part of the marketing authorisation.
• * On October 16, 2014, Boehringer Ingelheim announced that the FDA has approved Ofev™ (nintedanib*) for the treatment of idiopathic pulmonary fibrosis (IPF). Nintedanib* is taken as one capsule twice daily and will be available to patients within 10 days.
• The FDA-approval of nintedanib* is based on the findings from one Phase II trial (TOMORROW) and two Phase III trials (INPULSIS™-1 and INPULSIS™-2). The Phase II TOMORROW trial was a 12-month, randomised, double-blind, placebo-controlled trial conducted at 92 sites in 25 countries.5 The trial evaluated the safety and efficacy of oral nintedanib* at four dosage levels in 432 patients diagnosed with IPF, consistent with the criteria published by the American Thoracic Society (ATS) and European Respiratory Society (ERS). The primary endpoint for the TOMORROW trial was annual rate of decline in forced vital capacity (FVC).5 Secondary endpoints included acute exacerbations, quality of life measured with the St. Georges Respiratory Questionnaire (SGRQ) and total lung capacity. In patients treated with 150 mg twice daily nintedanib*, FVC declined by 0.06 litres per year as compared with 0.19 litres per year in patients treated with placebo.5 This dose also resulted in a lower incidence of acute exacerbations versus placebo (2.4 versus 15.7 per 100 patient years; p=0.02)5 and was also associated with a preserved quality of life when compared to placebo as measured by the SGRQ. Gastrointestinal side effects were common in the nintedanib* 150 mg bid group, but the majority of these effects were of mild or moderate intensity.5 Severe adverse events occurred with similar frequency in the placebo and active-treatment groups but numerically lower in the 150 mg twice daily dose group.
• •On July 16, 2014, Boehringer Ingelheim announced that the FDA has granted Breakthrough Therapy designation for nintedanib for treatment in idiopathic pulmonary fibrosis (IPF). Nintedanib is an investigational therapy currently under FDA and European Medicines Agency (EMA review) for IPF. Results from two global Phase III studies (INPULSIS™-1 and INPULSIS™-2) evaluating the efficacy and safety of nintedanib* for the treatment of IPF were presented at the American Thoracic Society (ATS) International Conference and published in the New England Journal of Medicine in May 2014.
• • On July 2, 2014, Boehringer Ingelheim Pharmaceuticals announced that the New Drug Application (NDA) for nintedanib has been accepted for filing by the FDA and granted Priority Review designation. The NDA package includes results from two global Phase 3 studies (INPULSIS™-1 and INPULSIS™-2) evaluating the efficacy and safety of nintedanib in the treatment of IPF. The INPULSIS™ studies were recently presented at the American Thoracic Society (ATS) International Conference and published in the New England Journal of Medicine.
• • On June 5, 2014, Boehringer Ingelheim has announced that the application for marketing authorisation of nintedanib* for the treatment of idiopathic pulmonary fibrosis has been validated and granted accelerated assessment by the European Medicines Agency (EMA).
• • On 26 April 2013, orphan designation (EU/3/13/1123) was granted by the European Commission to Boehringer Ingelheim International  for nintedanib for the treatment of idiopathic pulmonary fibrosis.
• • On March 12-13, 2013, the Committee for Orphan Medicinal Products has adopted a positive opinion recommending nintedanib for designation as an orphan medicinal product for treatment of idiopathic pulmonary fibrosis.

Patents:

Submission of marketing authorization application USA :

Submission of marketing authorization application UE:

Withdrawal of marketing authorization application USA:

Withdrawal of marketing authorization application UE:

US authorization: 2014-10-15

UE authorization: 2015-01-19

Favourable opinion UE: 2014-11-20

Favourable opinion USA:

Orphan status USA: 2011-06-29

Orphan status UE: 2013-04-26

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

Is general: Yes