Type of information: Granting of a Market Authorisation in the EU
Product name: Esbriet®
Therapeutic area: Lung diseases - Respiratory diseases - Rare diseases
- Esbriet® is an orally active, small molecule drug that inhibits the synthesis of TGF-beta, a chemical mediator that controls many cell functions including proliferation and differentiation, and plays a key role in fibrosis. It also inhibits the synthesis of TNF-alpha, a cytokine that is known to have an active role in inflammation.
- Esbriet® has been developed by InterMune, a Brisbane, California-based biotechnology company that dedicated itself to developing medicines for IPF and other serious diseases related to fibrosis. On September 29, 2014, Roche announced that they completed the acquisition of InterMune after a definitive merger agreement on August 24, 2014.
Company: Intermune (USA - CA) Genentech, a member of the Roche Group (USA - Switzerland)
Disease: mild to moderate idiopathic pulmonary fibrosis (IPF)
- • On October 24, 2014, Roche announced that Esbriet® (pirfenidone) has received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) for an update to its European prescribing information.
- The CHMP recommendation includes data from the phase III ASCEND study, which showed that the proportion of patients with ?10 percent decline in forced vital capacity (FVC) – a measure indicative of the risk of mortality in IPF – was significantly reduced in patients receiving Esbriet® compared with patients receiving placebo at one year.
- Also included in the label update is a pre-specified pooled analysis from ASCEND and the two phase III CAPACITY trials that showed that the risk of all-cause mortality was reduced by 48 percent in Esbriet®-treated patients compared with the placebo group at one year. The pooled analysis also showed that the risk of treatment-emergent IPF-related mortality in the Esbriet® group compared to placebo was reduced by 68 percent in the pooled population at one year. Following the CHMP positive opinion, the EU prescribing information will now be updated to include the ASCEND data.
- • On October 15, 2014, Genentech, a member of the Roche Group, announced that the FDA has approved Esbriet® (pirfenidone) as a treatment for idiopathic pulmonary fibrosis (IPF) in the United States. The approval of Esbriet® is based on data from a large, placebo-controlled Phase III study known as ASCEND and is supported by two other large Phase III trials known as CAPACITY 1 and 2. The most serious adverse events observed in people who received Esbriet® compared to those who received placebo were: elevations in liver enzymes found in the blood (a sign of liver damage; 3.7 percent vs. 0.8 percent), sensitivity to light or rash (9.0 percent vs. 1.0 percent) and gastrointestinal (GI) side effects that caused 2.2 percent of patients to discontinue treatment compared to 1.0 percent of those who received placebo.
- Esbriet® will be available to patients within two weeks. A comprehensive patient support program designed to help with access, financial support and ongoing education will be available for people who are prescribed Esbriet for IPF.
- • On July 17, 2014, InterMune announced that pirfenidone has been granted Breakthrough Therapy Designation from the FDA. In May, InterMune resubmitted its New Drug Application (NDA) for pirfenidone and noted a target FDA review of six months under the Prescription Drug User Fee Act.
- • On May 27, 2014, InterMune announced that it has resubmitted its pirfenidone NDA to the FDA in response to a Complete Response Letter (CRL) received in May 2010. In May 2010, InterMune received a CRL from the FDA. In the CRL, the FDA recommended an additional Phase 3 clinical trial to support the efficacy of pirfenidone. Since the receipt of the CRL, InterMune has conducted the Phase 3 ASCEND trial of pirfenidone in IPF, and results of that trial were presented on May 18, 2014, at the meeting of the American Thoracic Society and were published on-line the same day in the New England Journal of Medicine. The NDA resubmission includes the ASCEND Clinical Study Report as well as the pooled analyses of efficacy and mortality from the three InterMune Phase 3 trials: ASCEND and the previous Phase 3 CAPACITY trials (004 and 006).
- • On May 16,2014, Intermune has announced that the company intended to resubmit the pirfenidone New Drug Application (NDA) to the FDA in the coming weeks.
- • On June 14, 2013, InterMune has announced that the Board of the Italian Drug Agency (AIFA) has approved the pricing and reimbursement conditions for Esbriet® (pirfenidone), and that the agreement has been published in the Official Gazette, the official journal of the government of Italy. Esbriet® will be reimbursed beginning 15 days from the publication date on the Italian Official Gazette , or June 29 . The gross ex-factory price of Esbriet® in Italy will be €32,994, or approximately $44,000 per patient, per year. In addition, pharmaceutical products in Italy are subject to the mandatory national discount of 9.75%. Reimbursement for Esbriet® will be provided under a risk-sharing arrangement, similar to the "Payment for Performance" system already in place for many specialty medicines in Italy. The agreement with AIFA specifies that Esbriet may be prescribed by pulmonologists. Esbriet® will be reimbursed as a Hospital Product, Class H, and will be distributed, similarly to other specialty products, by the pharmacies of the hospitals designated by the Regions and Autonomous Provinces. Patients treated with Esbriet therapy will be recorded in a registry designed and maintained by AIFA to collect patient data and to ensure appropriate patient selection to fit the approved label.
- • On March 20, 2013, InterMune has announced that the National Institute for Health and Clinical Excellence (NICE), the health technology appraisal body in England and Wales, has issued its Final Appraisal Determination (FAD) recommending Esbriet® (pirfenidone) for the treatment of mild to moderate idiopathic pulmonary fibrosis. The NICE Appraisal Committee recommended pirfenidone as an option for treating IPF patients whose predicted forced vital capacity (FVC) is between 50 percent and 80 percent at the initiation of therapy. Treatment with pirfenidone for these patients should be discontinued if there is evidence of disease progression (as defined by a decline in percent predicted FVC of 10 percent or more within any 12-month period). Based on the clinical study experience with Esbriet, the company expects that between 10 and 15 percent of patients could meet this definition of disease progression in a given 12-month period. The FAD further recommends the prescription of Esbriet for as long as InterMune makes the Patient Access Scheme (PAS) available. The PAS is a confidential pricing and access agreement with the UK's Department of Health. The NHS list price for Esbriet is £26,100 per full year of treatment. At current rates of exchange this is equivalent to roughly €30,140 and $39,350 per patient per year. The FAD forms the basis of the final guidance to the NHS in England and Wales and is expected to be published in April of 2013. Once the final guidance is published, the NHS must fully implement it within 90 days.
- InterMune also reported that health authorities of the Pharmaceutical Pricing Board of Finland (HILA) have agreed to pricing and reimbursement for Esbriet in that country, effective June 1, 2013. Esbriet will be reimbursed for IPF patients whose predicted FVC is between 50 percent and 80 percent at the initiation of therapy. The pharmacy purchase price of Esbriet in Finland will be equivalent to approximately €26,900 per patient, per year, while the net ex-factory price realized by InterMune will be approximately €26,000, or about $33,900 per patient, per year at current exchange rates. An estimated 500 to 800 patients are estimated to be living with mild to moderate IPF in Finland.
- • On September 11, 2012, InterMune has reported that the Comite Economique des Produits de Sante (CEPS) has granted reimbursement for Esbriet® (pirfenidone), making it the first medicine for the treatment of idiopathic pulmonary fibrosis to be reimbursed in France. The price of Esbriet® is expected to be published in France 's Journal Officiel in the fourth quarter of 2012; the final step in the reimbursement process for a new medicine in France. The CEPS authorized an ex-factory reimbursed price of 1.923,08€ for a four-week treatment pack of Esbriet®, corresponding to 25,000€ per patient, per year (approximately $32,000 at current exchange rates). Esbriet® will be reimbursed by the French National Health Insurance system for the treatment of mild to moderate forms of IPF in adults. Esbriet® will be reimbursed as a "Medicament d'Exception," which means that it will be reimbursed only for the labeled indication, defined previously by the Commission de Transparence of the French High Health Authority (CT) as IPF patients with forced vital capacity (FVC) > 50% and carbon monoxide diffusing capacity (DLco) > 35%. In agreement with CEPS , InterMune France will collect information in the form of a patient registry regarding the use of Esbriet® in clinical practice. InterMune is conducting a Phase 3 study, ASCEND, to support the regulatory registration of Esbriet® for the treatment of IPF in the United States and expects to complete patient enrollment of the study around the end of 2012.
- • On April 5, 2012, InterMune announced that the Transparency Commission (CT: Commission de Transparence) of the French National Health Authority (HAS: Haute Autorite de Sante) has issued a favorable opinion for the reimbursement of Esbriet® by French National Health Insurance. The CT noted that no other treatment provided evidence of a clinical benefit in IPF and considering all available information, Esbriet® was granted an Amelioration du Service Medical Rendu (ASMR) rating of level IV. ASMR is a rating of added clinical value in comparison with existing therapies. The CT focused on the risk/benefit ratio for assessing the actual medical benefit (Service Medical Rendu SMR), and rated it as "Low." The CT also recommended that InterMune collect information in the form of a patient registry regarding the use of Esbriet in clinical practice. InterMune will now enter the next step in the process, which is to determine the price and any reimbursement conditions of Esbriet® in France with the CEPS (Comite Economique des Produits de Sante).
- • On March 15, 2012, InterMune reported that Germany's Federal Joint Committee (G-BA) has announced its decision granting the additional benefit of Esbriet® in adults for the treatment of mild-to-moderate idiopathic pulmonary fibrosis. Esbriet®'s additional benefit was classified as stage 4 (not quantifiable benefit) in the rating system established under Germany's AMNOG pharmaceutical law. A non-quantifiable benefit means that the drug has an additional benefit, which will be defined in the future via experience in daily clinical use or clinical studies. Based on this, a stage of 1-3 will be assigned. InterMune's next step is to enter price negotiations with the Statutory Health Insurance.
- • On September 12, 2011, InterMune has announced that Esbriet® will be offered to patients in Germany beginning September 15, 2011. This will mark the first time Esbriet® will be commercially available in Europe since it was approved by the European Commission.
- • On March 3, 2011, InterMune has announced that the European Commission has granted marketing authorization for Esbriet®. The drug is indicated in adults for the treatment of mild to moderate idiopathic pulmonary fibrosis. InterMune currently plans to launch Esbriet® in the so-called "Top 5" EU countries as follows: Germany in September of 2011; France, Spain and Italy in the first half of 2012 and in the United Kingdom in mid-2012. InterMune also plans to launch Esbriet® in all or substantially all of the 10 most important pharmaceutical markets in the EU by approximately mid-2012.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE: 2010-02-26
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2014-10-15
UE authorization: 2011-02-28
Favourable opinion UE: 2010-12-17
Favourable opinion USA:
Orphan status USA: 2004- 03-05
Orphan status UE: 2004-11-16
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
Other news: • On June 27, 2017, Roche announced that the European Commission has approved a new tablet formulation of Esbriet® (pirfenidone) for the treatment of mild to moderate idiopathic pulmonary fibrosis. Esbriet has been shown to slow the progression of IPF and the new tablet formulation, available as an 801 mg or 267 mg tablet, is designed to provide additional treatment options for people living with the disease.