REGULATORY UPDATE – CELSENTRI/SELZENTRY® (MARAVIROC)
ViiV Healthcare announced today that it has withdrawn its Type II Variation to the European Medicines Agency (EMEA) and its Supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for once-daily (QD) administration of Celsentri/Selzentry® (maraviroc) tablets in treatment-experienced patients infected with only CCR5-tropic HIV-1. The submission was based on a sub-analysis of the original registrational studies in treatment-experienced patients, MOTIVATE 1 & 2. Although ViiV Healthcare remains committed to studying the potential for once-daily dosing of Celsentri/Selzentry in treatment-experienced patients, we have concluded that additional data is necessary to establish the efficacy of once-daily dosing of Celsentri/Selzentry.
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.
INDICATION AND USAGE
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 with efavirenz
IMPORTANT SAFETY INFORMATION
WARNING: Hepatotoxicity: See full Prescribing Information for complete Boxed Warning.
Hepatotoxicity has been reported, which may be preceded by severe rash or other features of a systemic allergic reaction (eg, fever, 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
Hepatotoxicity accompanied by severe rash or systemic allergic reaction including potentially life-threatening events has been reported in clinical trials and postmarketing. These events occurred approximately one month after starting treatment. Among reported cases of hepatitis, some were observed in the absence of allergic features or with no pre-existing hepatic disease.
Hepatic laboratory parameters including ALT, AST, and bilirubin should be obtained prior to starting SELZENTRY and at other time points during treatment as clinically indicated. If rash or symptoms or signs of hepatitis or allergic reaction develop, hepatic laboratory parameters should be monitored and discontinuation of treatment should be considered.
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-naïve patients, the most common adverse events reported with SELZENTRY twice-daily therapy with frequency rates higher than efavirenz, regardless of causality, were bronchitis (13% vs 9%), upper respiratory tract infection (32% vs 30%), flatulence, bloating, and distention (10% vs 7%), upper respiratory tract signs and symptoms (9% vs 5%), GI atonic and hypomotility disorders not elsewhere classified (NEC) (9% vs 5%), and anemias NEC (8% vs 5%).
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 150-mg and 300-mg tablets.
|UK Media inquiries:||Rebecca Hunt
|(020) 8380 6275
(020) 8047 5502
|US Media inquiries:||Marc Meachem||(919) 483 5005|
|GSK European Analyst/Investor inquiries:||Sally Ferguson||(020) 8047 5543|
|Gary Davies||(020) 8047 5503|
|Ziba Shamsi||(020) 8047 3289|
|GSK US Analyst/ Investor inquiries:||Tom Curry||(215) 751 5419|
|Jeff McLaughlin||(215) 751 7002|
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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 2010.
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, 2010 and in its reports on Form 10-Q and Form 8-K.