Products

Date: 2015-01-19

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

Product name: Viekira®Pak

Compound: fixed-dose combination of ABT-450 (paritaprevir)/ritonavir (150/100mg) co-formulated with ombitasvir (ABT-267) 25mg, dosed once daily, and dasabuvir (ABT-333) 250mg

Therapeutic area: Infectious diseases

Action mechanism:

• direct-acting antiviral agent/protease inhibitor/RNA polymerase (NS5B) inhibitor/RNA polymerase (NS5A) inhibitor/NS3/4A protease inhibitor. The AbbVie investigational regimen consists of the fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ombitasvir (ABT-267) 25mg, dosed once daily, and dasabuvir (ABT-333) 250mg with or without RBV (weight-based), dosed twice daily. The combination of three different mechanisms of action interrupts the hepatitis C virus replication process with the goal of optimizing sustained virologic response rates across different patient populations. ABT-450 is an inhibitor of the HCV nonstructural 3/4A (NS3/4A) protease administered with the pharmacoenhancer ritonavir. It was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals. Ombitasvir is an HCV NS5A inhibitor. Dasabuvir is a nonnucleoside HCV NS5B RNA polymerase inhibitor.
• Six Phase III studies have included more than 2,300 patients in over 25 countries:

SAPPHIRE-I is a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of of the combination of ABT-450/ritonavir, ombitasvir and dasabuvir with ribavirin in treatment-naïve adults with genotype 1 chronic HCV infection (NCT01716585). Results of this study have been published in The New England Journal of Medicine on April 24, 2014. (Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. Jordan J. Feld and al. DOI:10.1056/NEJMoa1315722) SAPPHIRE-II is a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of combination of ABT-450/ritonavir, ombitasvir and dasabuvir with ribavirin in treatment-experienced adults with genotype 1 chronic HCV infection (NCT01715415). PEARL-II is is a randomized, open-label, multicenter study to evaluate the efficacy and safety of combination of ABT-450/ritonavir, ombitasvir and dasabuvir with and without ribavirin in treatment-experienced subjects with genotype 1b HCV infection (NCT01674725). PEARL-III is a randomized, double-blind, controlled study to evaluate the efficacy and safety of of the combination of ABT-450/ritonavir, ombitasvir and dasabuvir with and without ribavirin in treatment naive adults with genotype 1b chronic HCV infection (NCT01767116). PEARL-IV is a randomized, double-blind, controlled study to evaluate the efficacy and safety of of the combination of ABT-450/ritonavir, ombitasvir and dasabuvir with and without ribavirin in treatment naive adults with genotype 1a chronic HCV infection (NCT01833533). TURQUOISE-II is a phase III, randomized, open-label, international trial that evaluated safety and efficacy of the combination of ABT-450/ritonavir, ombitasvir and dasabuvir with ribavirin for 12 or 24 weeks in previously untreated and previously treated adults with chronic HCV genotype 1 infection and compensated cirrhosis (NCT01704755). Results of this study have been published in The New England Journal of Medicine on April 12, 2014 (ABT-450/r-ombitasvir and dasabuvir with ribavirin  for hepatitis C with cirrhosis. Fred Poordad and al. April 12, 2014 DOI:10.1056/NEJMoa1402869).

Company: Abbvie (USA - IL)

Disease: hepatitis C

Latest news:

• • On December 19, 2014, the FDA approved Viekira® Pak (ombitasvir, paritaprevir and ritonavir tablets co-packaged with dasabuvir tablets) to treat patients with chronic hepatitis C virus (HCV) genotype 1 infection, including those with a type of advanced liver disease called cirrhosis. Viekira® Pak contains three new drugs—ombitasvir, paritaprevir and dasabuvir—that work together to inhibit the growth of HCV. It also contains ritonavir, a previously approved drug, which is used to increase blood levels of paritaprevir. Viekira Pak can be used with or without ribavirin, but it is not recommended for patients whose liver is unable to function properly (decompensated cirrhosis).
• • On June 13, 2014, AbbVie announced that the New Drug Application (NDA) for its investigational, all-oral, interferon-free regimen for the treatment of adult patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection has been accepted by the FDA and has been granted priority review. The NDA was submitted on April 21, 2014 and is supported by data from a large clinical program including six Phase III studies of more than 2,300 GT1 patients in over 25 countries. The regimen was granted a Breakthrough Therapy designation by the FDA in May 2013, a status given to investigational treatments for serious or life-threatening conditions with preliminary clinical evidence demonstrating substantial improvement on at least one clinically significant endpoint compared to available therapy.
• * On May 8, 2014, AbbVie submitted marketing authorization applications (MAAs) to the European Medicines Agency (EMA) seeking approval for the company's investigational, all-oral, interferon-free regimen for the treatment of adult patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection. The MAAs are supported by data from a large all-oral, interferon-free clinical program in GT1 patients, which consists of six Phase III studies that include more than 2,300 patients in over 25 countries. The EMA has granted AbbVie's request for accelerated assessment for ABT-450/ritonavir, ombitasvir (ABT-267), and dasabuvir (ABT-333). Review of AbbVie's MAAs will be conducted under the centralized licensing procedure which, when finalized, provides one marketing authorization in all 28 member states of the European Union (EU).
• • On April 22, 2014, AbbVie has announced that it has submitted its New Drug Application (NDA) to the FDA seeking approval for the company's investigational, all-oral, interferon-free regimen for the treatment of adult patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection. The NDA is supported by data from the largest all-oral, interferon-free clinical program in GT1 patients conducted to date,1 with six Phase III studies that included more than 2,300 patients in over 25 countries.
• In May of 2013, AbbVie's investigational direct-acting antiviral (DAA) regimen with and without ribavirin for HCV genotype 1 was designated as a Breakthrough Therapy by the U.S. FDA. This designation is intended to help expedite the development of drugs for serious or life-threatening conditions and is based in part on preliminary clinical evidence demonstrating a drug or regimen may have substantial improvement on at least one clinically significant endpoint compared to available therapy. AbbVie plans to submit applications for regulatory approval of its regimen in the European Union in early May.

Patents:

Submission of marketing authorization application USA : 2014-04-21

Submission of marketing authorization application UE: 2014-05-08

Withdrawal of marketing authorization application USA:

Withdrawal of marketing authorization application UE:

US authorization: 2014-12-19

UE authorization: 2015-01-19

Favourable opinion UE: 2014-11-21

Favourable opinion USA:

Orphan status USA:

Orphan status UE:

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

• • On 26 July 2018, the CHMP adopted a positive opinion recommending a change to the terms of the marketing authorisation for Viekirax®. The full contraindications for Viekirax® will be as follows:
• “Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.
• Patients with moderate to severe hepatic impairment (Child-Pugh B or C) (see section 5.2).
• Use of ethinylestradiol-containing medicinal products such as those contained in most combined oral contraceptives or contraceptive vaginal rings (see section 4.4 and 4.5). Medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma levels are associated with serious events must not be co-administered with Viekirax (see section 4.5). Examples are provided below. CYP3A4 substrates: • alfuzosin hydrochloride • amiodarone, disopyramide, dronedarone, quinidine, ranolazine • astemizole, terfenadine • cisapride • colchicine in patients with renal or hepatic impairment • ergotamine, dihydroergotamine, ergonovine, methylergometrine • fusidic acid • lovastatin, simvastatin, atorvastatin • lurasidone • oral midazolam, triazolam • pimozide • quetiapine • salmeterol • sildenafil (when used for the treatment of pulmonary arterial hypertension) • ticagrelor Co-administration of Viekirax with or without dasabuvir with medicinal products that are strong or moderate enzyme inducers is expected to decrease ombitasvir, paritaprevir, and ritonavir plasma concentrations and reduce their therapeutic effect and must not be co-administered (see section 4.5). Examples of contraindicated strong or moderate enzyme inducers are provided below. Enzyme inducers: • carbamazepine, phenytoin, phenobarbital • efavirenz, nevirapine, etravirine • enzalutamide • mitotane • rifampicin • St. John’s Wort (Hypericum perforatum) Co-administration of Viekirax with or without dasabuvir with medicinal products that are strong inhibitors of CYP3A4 is expected to increase paritaprevir plasma concentrations and must not be co-administered with Viekirax (see section 4.5). Examples of contraindicated strong CYP3A4 inhibitors are provided below. CYP3A4 inhibitors: • cobicistat • indinavir, lopinavir/ritonavir, saquinavir, tipranavir, • itraconazole, ketoconazole, posaconazole, voriconazole • clarithromycin, telithromycin • conivaptan”
• • On October 22, 2015, the FDA has warned that hepatitis C treatments Viekira Pak® and Technivie® can cause serious liver injury mostly in patients with underlying advanced liver disease. As a result, the agency has required the manufacturer to add new information about this safety risk to the drug labels. Patients taking these medicines should contact their health care professional immediately if they develop fatigue, weakness, loss of appetite, nausea and vomiting, yellow eyes or skin, or light-colored stools, as these may be signs of liver injury. Patients should not stop taking these medicines without first talking to their health care professionals. Stopping treatment early could result in drug resistance to other hepatitis C medicines. Health care professionals should closely monitor for signs and symptoms of worsening liver disease, such as ascites, hepatic encephalopathy, variceal hemorrhage, and/or increases in direct bilirubin in the blood.

Is general: Yes