Tibotec Pharmaceuticals Announces Agreement With Gilead Sciencesto Develop and Commercialize a New Fixed-Dose Combination of PREZISTA® andCobicistat
CORK,Ireland, June 28, 2011 -- Tibotec Pharmaceuticals todayannounced that it has entered into a license agreement with Gilead Sciences,Inc., for the development and commercialization of a new once-daily singletablet fixed-dose antiretroviral combination product containing Tibotec'sprotease inhibitor PREZISTA® (darunavir) and Gilead's cobicistat, aninvestigational pharmacoenhancing or "boosting" agent.
PREZISTA,co-administered with ritonavir (PREZISTA/ritonavir), and with otherantiretroviral agents, is indicated for the treatment of human immunodeficiencyvirus (HIV-1) infection. In the United States of America, once dailydosing of PREZISTA is indicated for treatment-naive adult patients andtreatment-experienced adult patients with no darunavir resistance associated substitutions. In the European Union once daily dosing of PREZISTA is recommended fortreatment-naive adult patients and may be used in treatment-experienced adultpatients with no darunavir resistance associated substitutions and who haveplasma HIV-1 RNA < 100,000 copies/ml and CD4+ cell count greater than orequal to 100 cells x 10(6)/l.
"Weare excited to be able to study and develop PREZISTA with an alternativeboosting agent in a combination product which has the potential to reduce thenumber of tablets patients take. Tibotec is committed to developing newand innovative HIV treatment options, especially those which provide simplifiedtreatment regimens that may help patients to better manage their HIV treatment. PREZISTA is one of the leading protease inhibitors and co-formulating itwith cobicistat in a new combination product demonstrates our commitment to HIVand innovations that will provide new options for patients," said JohanVan Hoof, MD, Global Therapeutic Area Head, Infectious Diseases and Vaccines,Janssen Pharmaceutica N.V.
Subjectto regulatory approval, Tibotec will be responsible for the formulation,manufacturing, registration, distribution and commercialization of the PREZISTAand cobicistat fixed-dose combination worldwide. Gilead retains solerights for the manufacture, development and commercialization of cobicistat asa stand-alone product and for use in combination with other agents.
Inconnection with this agreement, the companies are also negotiating terms forthe development and commercialization of a future single-tablet regimen (STR)combining PREZISTA with Gilead's Emtriva® (emtricitabine), and itsinvestigational agents GS 7340 and cobicistat. Gilead would beresponsible for the development and commercialization of the new STR on aworldwide basis. The agreement to develop the fixed-dose combination ofcobicistat and PREZISTA is contingent upon the signing of an agreement on theEmtriva, GS 7340, cobicistat and PREZISTA STR.
PREZISTA®,co-administered with ritonavir (PREZISTA/ritonavir), and with otherantiretroviral agents, is indicated for the treatment of human immunodeficiencyvirus (HIV-1) infection. This indication is based on analyses of plasmaHIV-1 RNA levels and CD4+ cell counts from 2 controlled Phase 3 trials of 48weeks duration in antiretroviral treatment-naive and treatment-experiencedpatients and 2 controlled Phase 2 trials of 96 weeks duration in clinicallyadvanced, treatment-experienced adult patients.
Intreatment-experienced adults, the following points should be considered wheninitiating therapy with PREZISTA/ritonavir:
- Treatment history and, when available, genotypic or phenotypictesting should guide the use of PREZISTA/ritonavir.
- The use of other active agents with PREZISTA/ritonavir isassociated with a greater likelihood of treatment response.
PREZISTAdoes not cure HIV-1 infection or AIDS, and does not prevent passing HIV-1 toothers.
- Coadministration of PREZISTA/ritonavir is contraindicated withdrugs that are highly dependent on CYP3A for clearance and for which elevatedplasma concentrations are associated with serious and/or life-threateningevents (e.g., alfuzosin, dihydroergotamine, ergonovine, ergotamine,methylergonovine, cisapride, pimozide, oral midazolam, triazolam, lovastatin,or simvastatin).
- Coadministration of PREZISTA/ritonavir is also contraindicatedwith rifampin and products containing St. John's wort (Hypericum perforatum)because this may cause significant decrease in plasma concentration ofdarunavir, resulting in loss of therapeutic effect and development ofresistance.
- 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 inpatients receiving PREZISTA/ritonavir.
- This list of potential drug interactions isnot complete.
- PREZISTA must be coadministered with ritonavir and food to achievethe desired antiviral effect. Failure to administer PREZISTA with ritonavir andfood may result in a loss of efficacy of darunavir. Please refer toritonavir prescribing information for additional information on precautionarymeasures.
- Drug-induced hepatitis (e.g.,acute hepatitis, cytolytic hepatitis) has been reported withPREZISTA/ritonavir. During the clinical development program (N=3063),hepatitis has been reported in 0.5% of patients receiving combination therapywith PREZISTA/ritonavir. Patients with preexisting liver dysfunction,including chronic active hepatitis B or C, have an increased risk for liverfunction abnormalities, including severe hepatic adverse events.
Post-marketing cases of liver injury, including some fatalities,have been reported. A causal relationship with PREZISTA/ritonavir therapyhas not been established
Appropriate laboratory testing should be conducted prior toinitiating therapy with PREZISTA/ritonavir and patients should be monitoredduring treatment. Increased AST/ALT monitoring should be considered inpatients with underlying chronic hepatitis, cirrhosis, or in patients who havepretreatment elevations of transaminases, especially during the first severalmonths of PREZISTA/ritonavir treatment. Evidence of new or worseningliver dysfunction (including clinically significant elevation of liver enzymesand/or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, livertenderness, hepatomegaly) in patients on PREZISTA/ritonavir should promptconsideration of interruption or discontinuation of treatment
- Severe Skin Reactions: Severeskin reactions (0.4%), accompanied by fever and/or elevations of transaminasesin some cases, Stevens-Johnson Syndrome (<0.1%), and toxic epidermalnecrolysis (post-marketing experience) have been reported in patients receivingPREZISTA/ritonavir. Discontinue PREZISTA/ritonavir immediately if signsor symptoms of severe skin reactions develop (including, but not limited to,severe rash or rash accompanied with fever, general malaise, fatigue, muscle orjoin aches, blisters, oral lesions, conjunctivitis, hepatitis and/oreosinophilia).
In clinical trials (N=3063), rash (all grades, generally mild to moderate,regardless of causality) occurred in 10.3% of patients receivingPREZISTA/ritonavir. Discontinuation due to rash was 0.5%.
- Sulfa Allergy: PREZISTAshould be used with caution in patients with known sulfonamide allergy.
- Diabetes Mellitus/Hyperglycemia andHemophilia: New-onset or exacerbations of preexisting diabetes mellitus,hyperglycemia, and increased bleeding in hemophiliacs have been reported inpatients receiving protease inhibitors. Initiation or dose adjustments ofinsulin or oral hypoglycemic agents may be required. A causalrelationship between protease inhibitors and these events has not beenestablished.
- Fat Redistribution:Redistribution and/or accumulation of body fat have been observed in patientsreceiving ARV therapy. The causal relationship, mechanism, and long-termconsequences of these events have not been established.
- Immune reconstitution syndrome has beenreported in patients treated with ARV therapy.
- Resistance/Cross Resistance: Thepotential for HIV-1 cross-resistance among protease inhibitors has not beenfully explored in PREZISTA/ritonavir-treated patients.
Use inSpecific Populations
- Hepatic Impairment:PREZISTA/ritonavir is not recommended for use in patients with severe hepaticimpairment. There are no pharmacokinetic or safety data available inpatients with severe hepatic impairment.
- Pregnancy: PREZISTA should be usedduring pregnancy only if the potential benefit justifies the potential risk. No adequate and well-controlled studies have been conducted in pregnantwomen.
- In treatment-naive adult patients, themost common adverse drug reactions (greater than or equal to 5%) reported of atleast moderate intensity (greater than or equal to Grade 2) in thePREZISTA/ritonavir arm through 96 weeks were diarrhea (8%), headache(6%), abdominal pain (5%), and rash (5%).
- In treatment-experienced adult patients, themost common adverse drug reactions (greater than or equal to 5%) reported of atleast moderate intensity (greater than or equal to Grade 2) in thePREZISTA/ritonavir arm through 96 weeks were diarrhea (14%), nausea (7%), rash(7%), abdominal pain (6%), and vomiting (5%).
This isnot a complete list of all adverse drug reactions reported with the use ofPREZISTA/ritonavir.
Pleasesee accompanying full Prescribing Information for more details. Fullprescribing information is also available at www.PREZISTA.com.
You areencouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, orcall 1-800-FDA-1088.
TibotecPharmaceuticals is a global pharmaceutical and research development company andone of the companies that compose the Janssen Pharmaceutical Companies ofJohnson & Johnson. The Company's main research and developmentfacilities are in Beerse, Belgium with offices in Titusville, NJ and Cork,Ireland. Tibotec is dedicated to the discovery and development of innovativeHIV/AIDS and hepatitis C drugs, and anti-infectives for diseases of high unmetmedical need.