Once Daily Administration of Maraviroc Submitted to EMA & FDA
Regulatory Update - Celsentri/Selzentry® (maraviroc)|
04 March 2011
London, UK, 04 March 2011 - ViiV Healthcare LLC announced today that it has submitted a Type II Variation to the European Medicines Agency (EMA) and a Supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for once daily administration of Celsentri/Selzentry® (maraviroc) 150 mg tablets in treatment-experienced patients infected with CCR5-tropic HIV-1. The once-daily dosing would only be for regimens containing certain boosted protease inhibitors without a CYP3A inducer. CYP3A is an enzyme that aids in the metabolism of certain medications.
About ViiV Healthcare
ViiV Healthcare is a global specialist HIV company established in November 2009 by GlaxoSmithKline (NYSE: GSK) and Pfizer (NYSE: PFE) dedicated to delivering advances in treatment and care for people living with HIV. Our aim is to take a deeper and broader interest in HIV/AIDS than any company has done before and take a new approach to deliver effective and new HIV medicines as well as support communities affected by HIV. For more information on the company, its management, portfolio, pipeline and commitment, please visit www.viivhealthcare.com.
SELZENTRY® (maraviroc) is a first-in-class oral CCR5 entry inhibitor approved in the U.S. for both treatment-naïve and treatment-experienced adult patients with CCR5-tropic HIV-1 virus in combination with other anti-HIV medicines. SELZENTRY is known as CELSENTRI® outside of the U.S. where it is indicated for appropriate treatment-experienced patients. The currently-approved dosing is twice daily, with the amount of SELZENTRY varying based on a patient's concomitant medications and level of renal function. Use of SELZENTRY in patients with dual/mixed or CXCR4-tropic HIV-1 is not recommended. SELZENTRY will not cure HIV infection.
SELZENTRY, in combination with other antiretroviral agents, is indicated for adult patients infected with only CCR5-tropic HIV-1.
This indication is based on analyses of plasma HIV-1 RNA levels in two controlled studies of SELZENTRY in treatment-experienced patients and one study in treatment-naive patients. Both studies in treatment-experienced patients were conducted in clinically advanced, 3-class antiretroviral-experienced (NRTI, NNRTI, PI, or enfuvirtide) adults with evidence of HIV-1 replication despite ongoing antiretroviral therapy.
The following points should be considered when initiating therapy with SELZENTRY:
· Adult patients infected with only CCR5-tropic HIV-1 should use SELZENTRY
· Tropism testing must be conducted with a highly sensitive tropism assay that has demonstrated the ability to identify patients appropriate for SELZENTRY use. Outgrowth of pre-existing low-level CXCR4- or dual/mixed-tropic HIV-1 not detected by tropism testing at screening has been associated with virologic failure on SELZENTRY
· Use of SELZENTRY is not recommended in patients with dual/mixed or CXCR4-tropic HIV-1 as efficacy was not demonstrated in a Phase 2 study of this patient group
· The safety and efficacy of SELZENTRY have not been established in pediatric patients
· In treatment-naive patients, more patients treated with SELZENTRY experienced virologic failure and developed lamivudine resistance compared to efavirenz
IMPORTANT SAFETY INFORMATION
WARNING: Hepatotoxicity: See full Prescribing Information for complete Boxed Warning.
Hepatotoxicity has been reported, which may be preceded by evidence of a systemic allergic reaction (eg, pruritic rash, eosinophilia or elevated IgE). Immediately evaluate patients with signs or symptoms of hepatitis or allergic reaction.
SELZENTRY should not be used in patients with severe renal impairment or end-stage renal disease (ESRD) (CrCl < 30 mL/min) who are taking potent CYP3A inhibitors or inducers.
ADDITIONAL WARNINGS AND PRECAUTIONS
Discontinuation of SELZENTRY should be considered in any patient with signs or symptoms of hepatitis, or with increased liver transaminases combined with rash or other systemic symptoms.
The safety and efficacy of SELZENTRY have not been specifically studied in patients with significant underlying liver disorders such as patients co-infected with viral hepatitis B or C. Caution should be used when administering SELZENTRY to patients with pre-existing liver dysfunction or who are co-infected with viral hepatitis B or C.
Use with caution in patients at increased risk of cardiovascular events because cardiovascular events, including myocardial ischemia and/or infarction, were observed in treatment-experienced and treatment-naive patients who received SELZENTRY.
Caution should be used when administering SELZENTRY in patients with a history of postural hypotension or who receive concomitant medication known to lower blood pressure. Patients should be advised that if they experience dizziness while receiving SELZENTRY, they should avoid driving or operating machinery.
Postural hypotension in patients with renal impairment
SELZENTRY should not be used in patients with severe renal impairment or end-stage renal disease (ESRD) (CrCl < 30 mL/min) who are taking potent CYP3A inhibitors or inducers due to an increased risk of postural hypotension as a result of increased SELZENTRY exposure in some patients.
SELZENTRY should be used in patients with severe renal impairment or ESRD only if they are not receiving a concomitant potent CYP3A inhibitor or inducer and no alternative treatment options are available. If patients with severe renal impairment or end-stage renal disease (ESRD) not receiving a concomitant potent CYP3A inhibitor or inducer experience any symptoms of postural hypotension while taking SELZENTRY 300 mg twice daily the dose should be reduced to 150 mg twice daily.
Immune reconstitution syndrome
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including SELZENTRY.
Potential risk of infection
SELZENTRY antagonizes the CCR5 co-receptor located on some immune cells, and therefore could potentially increase the risk of developing infections. Patients should be monitored closely for evidence of infection while receiving SELZENTRY.
Potential risk of malignancy
While no increase in malignancy has been observed with SELZENTRY, due to this drug's mechanism of action it could affect immune surveillance and lead to an increased risk of malignancy. Long-term follow-up is needed to more fully assess this risk.
In treatment-experienced patients, the most common adverse events reported with SELZENTRY twice-daily therapy with frequency rates higher than placebo, regardless of causality, were upper respiratory tract infections (23% vs 13%), cough (14% vs 5%), pyrexia (13% vs 9%), rash (11% vs 5%), and dizziness (9% vs 8%).
In treatment-naive patients, the most common adverse events occurring at ≥2% for the SELZENTRY group, and at a higher rate than in the efavirenz group, regardless of causality, were anemias not elsewhere classified (NEC) (8% vs 5%), flatulence, bloating, and distention (10% vs 7%), GI atonic and hypomotility disorders NEC (9% vs 5%), bronchitis (13% vs 9%), bacterial infections NEC (6% vs 3%), upper respiratory tract signs and symptoms (9% vs 5%), nail and nail bed conditions (6% vs 2%), excluding infections and infestations and Neisseria infections (3% vs 0%).
USE IN SPECIFIC PATIENT POPULATIONS
Pediatric Patients: There are no data available in pediatric patients; therefore, SELZENTRY should not be used in patients <16 years of age.
Hepatic Impairment: SELZENTRY is principally metabolized by the liver; therefore, caution should be exercised when administering this drug to patients with hepatic impairment, because SELZENTRY concentrations may be increased.
SELZENTRY is a substrate of CYP3A and Pgp. Coadministration with potent CYP3A inhibitors, including protease inhibitors (except tipranavir/ritonavir) or delavirdine, will increase the concentration of SELZENTRY. Coadministration with potent CYP3A inducers, including efavirenz, may decrease the concentration of SELZENTRY. Healthcare Providers should ensure that an appropriate dose adjustment of SELZENTRY is made when SELZENTRY is coadministered with potent CYP3A inhibitors and/or potent CYP3A inducers since concentrations, therapeutic effects, and the safety of SELZENTRY may be affected.
Concomitant use of SELZENTRY and St. John's wort (Hypericum perforatum) or products containing St. John's wort is not recommended.
SELZENTRY is available in 150mg and 300mg tablets.
For additional important information about SELZENTRY, please visit www.selzentry.com.
Cautionary statement regarding forward-looking statements
GlaxoSmithKline disclosure notice: Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK' s operations are described under 'Risk Factors' in the 'Business Review' in the company' s Annual Report on Form 20-F for 2009.
Pfizer disclosure notice: Pfizer assumes no obligation to update any forward-looking statements contained in this release as a result of new information or future events or developments.
This release contains forward-looking information about Pfizer, GlaxoSmithKline and ViiV Healthcare and about the prospects of the companies, including revenues from in-line products and the potential benefits of product candidates that will be contributed to that company, as well as the potential financial impact of the transaction. Such information involves substantial risks and uncertainties including, among other things, decisions by regulatory authorities regarding whether and when to approve any drug applications that have been or may be filed for such product candidates as well as their decisions regarding labeling and other matters that could affect the availability or commercial potential of such product candidates; and competitive developments.
A further list and description of risks and uncertainties can be found in Pfizer's Annual Report of Form 10-K for the fiscal year ended December 31, 2009 and in its reports on Form 10-Q and Form 8-K.