CORK, Ireland, 28 June , 2011 – Tibotec Pharmaceuticals today announced that it has entered into a license agreement with Gilead Sciences, Inc., for the development and commercialization of a new once-daily single tablet fixed-dose antiretroviral combination product containing Tibotec’s protease inhibitor PREZISTA® (darunavir) and Gilead’s cobicistat, an investigational pharmacoenhancing or "boosting" agent.
PREZISTA, co-administered with ritonavir (PREZISTA/ritonavir), and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV-1) infection.
In the United States of America, once daily dosing of PREZISTA is indicated for treatment-naïve adult patients and treatment-experienced adult patients with no darunavir resistance associated substitutions. In the European Union once daily dosing of PREZISTA is recommended for treatment-naive adult patients and may be used in treatment-experienced adult patients with no darunavir resistance associated substitutions and who have plasma HIV-1 RNA < 100,000 copies/ml and CD4+ cell count ≥ 100 cells x 106/l.
“We are excited to be able to study and develop PREZISTA with an alternative boosting agent in a combination product which has the potential to reduce the number of tablets patients take. Tibotec is committed to developing new and innovative HIV treatment options, especially those which provide simplified treatment regimens that may help patients to better manage their HIV treatment. PREZISTA is one of the leading protease inhibitors and co-formulating it with cobicistat in a new combination product demonstrates our commitment to HIV and innovations that will provide new options for patients ,” said Johan Van Hoof, MD, Global Therapeutic Area Head, Infectious Diseases and Vaccines, Janssen Pharmaceutica N.V.
Subject to regulatory approval, Tibotec will be responsible for the formulation, manufacturing, registration, distribution and commercialization of the PREZISTA and cobicistat fixed-dose combination worldwide. Gilead retains sole rights for the manufacture, development and commercialization of cobicistat as a stand-alone product and for use in combination with other agents.
In connection with this agreement, the companies are also negotiating terms for the development and commercialization of a future single-tablet regimen (STR) combining Prezista with Gilead’s Emtriva® (emtricitabine), and its investigational agents GS 7340 and cobicistat. Gilead would be responsible for the development and commercialization of the new STR on a worldwide basis. The agreement to develop the fixed-dose combination of cobicistat and PREZISTA is contingent upon the signing of an agreement on the Emtriva, GS 7340, cobicistat and PREZISTA STR.
PREZISTA®, co-administered with ritonavir (PREZISTA/ritonavir), and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV-1) infection.
This indication is based on analyses of plasma HIV-1 RNA levels and CD4+ cell counts from 2 controlled Phase 3 trials of 48 weeks duration in antiretroviral treatment-naïve and treatment-experienced patients and 2 controlled Phase 2 trials of 96 weeks duration in clinically advanced, treatment-experienced adult patients
In treatment-experienced adult, the following points should be considered when initiating therapy with PREZISTA/ritonavir:
- Treatment history and, when available, genotypic or phenotypic testing should guide the use of PREZISTA/ritonavir.
- The use of other active agents with PREZISTA/ritonavir is associated with a greater likelihood of treatment response.
Important Safety Information
PREZISTA does not cure HIV-1 infection or AIDS, and does not prevent passing HIV-1 to others.
- Coadministration of PREZISTA/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., alfuzosin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, pimozide, oral midazolam, triazolam, lovastatin, or simvastatin)
- Coadministration of PREZISTA/ritonavir is also contraindicated with rifampin and products containing St. John’s wort (Hypericum perforatum) because this may cause significant decrease in plasma concentration of darunavir, resulting in loss of therapeutic effect and development of resistance
- Coadministration is not recommended with indinavir, lopinavir/ritonavir, saquinavir, and pravastatin
- Caution should be used when prescribing agents such as sildenafil, vardenafil, tadalafil, or other substrates, inhibitors, or inducers of CYP3A in patients receiving PREZISTA/ritonavir.
- This list of potential drug interactions is not complete.
Warnings & Precautions
- PREZISTA must be coadministered with ritonavir and food to achieve the desired antiviral effect. Failure to administer PREZISTA with ritonavir and food may result in a loss of efficacy of darunavir. Please refer to ritonavir prescribing information for additional information on precautionary measures
- Drug-induced hepatitis (e.g., acute hepatitis, cytolytic hepatitis) has been reported with PREZISTA/ritonavir. During the clinical development program (N=3063), hepatitis has been reported in 0.5% of patients receiving combination therapy with PREZISTA/ritonavir. Patients with preexisting liver dysfunction, including chronic active hepatitis B or C, have an increased risk for liver function abnormalities, including severe hepatic adverse events
Post-marketing cases of liver injury, including some fatalities, have been reported. A causal relationship with PREZISTA/ritonavir therapy has not been established
Appropriate laboratory testing should be conducted prior to initiating therapy with PREZISTA/ritonavir and patients should be monitored during treatment. Increased AST/ALT monitoring should be considered in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pretreatment elevations of transaminases, especially during the first several months of PREZISTA/ritonavir treatment. Evidence of new or worsening liver dysfunction (including clinically significant elevation of liver enzymes and/or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, hepatomegaly) in patients on PREZISTA/ritonavir should prompt consideration of interruption or discontinuation of treatment
- Severe Skin Reactions: Severe skin reactions (0.4%), accompanied by fever and/or elevations of transaminases in some cases, Stevens-Johnson Syndrome (<0.1%), and toxic epidermal necrolysis (post-marketing experience) have been reported in patients receiving PREZISTA/ritonavir. Discontinue PREZISTA/ritonavir immediately if signs or symptoms of severe skin reactions develop (including, but not limited to, severe rash or rash accompanied with fever, general malaise, fatigue, muscle or join aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia)
In clinical trials (N=3063), rash (all grades, generally mild to moderate, regardless of causality) occurred in 10.3% of patients receiving PREZISTA/ritonavir. Discontinuation due to rash was 0.5%
- Sulfa Allergy: PREZISTA should be used with caution in patients with known sulfonamide allergy
- Diabetes Mellitus/Hyperglycemia and Hemophilia: New-onset or exacerbations of preexisting diabetes mellitus, hyperglycemia, and increased bleeding in hemophiliacs have been reported in patients receiving protease inhibitors. Initiation or dose adjustments of insulin or oral hypoglycemic agents may be required. A causal relationship between protease inhibitors and these events has not been established
- Fat Redistribution: Redistribution and/or accumulation of body fat have been observed in patients receiving ARV therapy. The causal relationship, mechanism, and long-term consequences of these events have not been established
- Immune reconstitution syndrome has been reported in patients treated with ARV therapy
- Resistance/Cross Resistance: The potential for HIV-1 cross-resistance among protease inhibitors has not been fully explored in PREZISTA/ritonavir-treated patients
Use in Specific Populations
- Hepatic Impairment: PREZISTA/ritonavir is not recommended for use in patients with severe hepatic impairment. There are no pharmacokinetic or safety data available in patients with severe hepatic impairment
- Pregnancy: PREZISTA should be used during pregnancy only if the potential benefit justifies the potential risk. No adequate and well-controlled studies have been conducted in pregnant women
- In treatment-naïve adult patients, the most common adverse drug reactions (³5%) reported of at least moderate intensity (≥Grade 2) in the PREZISTA/ritonavir arm through 96 weeks were diarrhea (8%), headache (6%), abdominal pain (5%), and rash (5%)
- In treatment-experienced adult patients, the most common adverse drug reactions (³5%) reported of at least moderate intensity (≥Grade 2) in the PREZISTA/ritonavir arm through 96 weeks were diarrhea (14%), nausea (7%), rash (7%), abdominal pain (6%), and vomiting (5%)
This is not a complete list of all adverse drug reactions reported with the use of PREZISTA/ritonavir
Please see accompanying full Prescribing Information for more details. Full prescribing information is also available at www.PREZISTA.com.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
Tibotec Pharmaceuticals is a global pharmaceutical and research development company and one of the companies that compose the Janssen Pharmaceutical Companies of Johnson & Johnson. The Company’s main research and development facilities are in Beerse, Belgium with offices in Titusville, NJ and Cork, Ireland. Tibotec is dedicated to the discovery and development of innovative HIV/AIDS and hepatitis C drugs, and anti-infectives for diseases of high unmet medical need.
This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Tibotec Pharmaceuticals and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to, general industry conditions and competition; economic factors, such as interest rate and currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws and regulations; trends toward health care cost containment; and increased scrutiny of the healthcare industry by government agencies. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended January 2, 2011. Copies of this Form 10-K, as well as subsequent filings, are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. Neither Tibotec Pharmaceuticals nor Johnson & Johnson undertake to update any forward-looking statements as a result of new information or future events or developments.
Stan Panasewicz, Investor Relations
Louise Mehrotra, Investor Relations
Karen Manson, Media
+32 479 89 47 99 (mobile)