Lo studio Illuminate, pubblicato sul New England Journal of Medicine, ha dimostrato la non inferiorità del regime terapeutico a base di telaprevir della durata di 24 settimane rispetto a quello di 48 settimane.
Sono stati pubblicato sul New England Journal of Medicine i risultati dello studio clinico di Fase III Illuminate, che ha analizzato la risposta dei pazienti naïve affetti da epatite C cronica di genotipo 1 alla terapia con telaprevir, in combinazione con interferone pegilato e ribavirina.
Il trial ha dimostrato la non inferiorità del regime terapeutico a base di telaprevir della durata di 24 settimane rispetto a quello di 48 settimane, nei pazienti che hanno ottenuto una risposta virologica rapida estesa (eRVR ) o con Hcv RNA non rilevabile alla quarta e alla dodicesima settimana di trattamento. Con i regimi terapeutici a base di telaprevir si è ottenuta una risposta virologica rapida estesa (eRVR) nella maggioranza dei pazienti analizzati (65%).
“Questi risultati confermano i benefici del regime terapeutico a base di telaprevir in pazienti naïve con infezione da Hcv di genotipo 1”, ha affermato uno dei ricercatori, Kenneth Sherman, direttore della Divisione Digestive Diseases alla UC Health di Cincinnati (Usa). “La maggior parte dei pazienti, se trattati con telaprevir, potrebbe vedersi dimezzare la durata del trattamento, rispetto alla terapia standard”.
“Il percorso terapeutico a base di interferone pegilato e ribavirina - ha spiegato - è piuttosto lungo (generalmente 48 settimane), ma risulta efficace in meno della metà dei pazienti. La durata del trattamento, infatti, può portare a una minore aderenza alla terapia e al conseguente fallimento della stessa. La possibilità di dimezzare le tempistiche, senza compromettere l’efficacia della terapia, non potrà che migliorare i risultati clinici dei pazienti”, ha concluso.
Tutti pazienti che hanno completato lo studio hanno ricevuto fino alla dodicesima settimana telaprevir, in combinazione con interferone pegilato e ribavirina, e in seguito hanno assunto interferone pegilato e ribavirina da soli, per una durata totale del trattamento di 24 o 48 settimane.
I risultati dimostrano che, dei pazienti che hanno ottenuto una risposta virologica rapida estesa (eRVR), il 92% di quelli appartenenti al gruppo trattato per 24 settimane ha raggiunto una risposta virologica sostenuta o è guarito rispetto all’88% di quelli del gruppo trattato per 48 settimane. I pazienti che non hanno ottenuto una risposta virologica rapida estesa sono stati assegnati al trattamento completo della durata di 48 settimane. Di questi, il 64% ha ottenuto una risposta virologica sostenuta.
Questi dati, insieme a quelli degli studi Advance e Realize, costituiscono la base della richiesta di autorizzazione all’immissione in commercio di telaprevir, già sottoposta all’Ema. Il Comitato per i Prodotti Medicinali per Uso Umano aveva inoltre concesso la procedura di valutazione accelerata e il 22 luglio scorso ha espresso parere positivo per l’indicazione del farmaco nel trattamento dell’infezione da Hcv cronica di genotipo 1, in pazienti adulti con malattia epatica compensata (inclusa la cirrosi) naïve o che avevano fallito un precedente trattamento con interferone pegilato alfa da solo o in combinazione con ribavirina.
L’ingresso degli antivirali ad azione diretta (DAA), primo trattamento innovativo degli ultimi 10 anni, rappresenta un significativo passo in avanti, oltre che una nuova speranza di guarigione offerta ai pazienti affetti da Epatite C” afferma Charles Gore, del World Hepatitis Alliance. Il profilo generale di sicurezza di telaprevir è derivato dal programma di Studi clinici di Fase II/III. In questi studi l’incidenza di eventi avversi di intensità moderata è stata più alta nel gruppo che ha assunto telaprevir rispetto al gruppo placebo (entrambi i gruppi hanno ricevuto interferone alfa pegilato e ribavirina).
Le reazioni avverse moderate riportate più di frequente (incidenza ≥ 5,0%) sono state anemia, rash cutaneo, prurito, nausea e diarrea, mentre gli eventi avversi più frequenti di grado severo (incidenza ≥ 1,0%) sono stati anemia, rash cutaneo, trombocitopenia, linfopenia, prurito e nausea. 4 Il rash è stato riportato dal 55% dei pazienti trattati con telaprevir e più del 90% degli episodi andava da un grado di severità da lieve a moderato. Rash severi sono stati riportati nel 4,8% dei pazienti trattati con telaprevir. Questo evento avverso ha determinato la sospensione del trattamento nel 5,8% dei pazienti. L’anemia si è presentata nel 32,1% dei casi ed ha causato la sospensione del trattamento nel 3% circa dei pazienti.
“Siamo felici che la Commissione Europea abbia approvato telaprevir, e ciò che possiamo offrire ora ai pazienti è un significativo miglioramento della terapia per l’infezione da HCV, rispetto ai trattamenti standard” ha dichiarato Ramon Polo, Team Leader per lo sviluppo della molecola telaprevir. “Il farmaco rappresenta un momento di svolta per Janssen che sta ampliando il suo portafoglio di farmaci per il trattamento delle patologie infettive, che includono terapie anti HIV, tubercolosi, infezioni severe ed ora l’HCV, aiutando a ridefinire ed aumentare i risultati clinici dei trattamenti. Janssen continuerà a dedicarsi al miglioramento della qualità della vita dei pazienti e a supportare la comunità medico scientifica in tutto il mondo”. Telaprevir sarà commercializzato da Janssen in tutti i Paesi dell’Unione Europea con il nome commerciale di INCIVO®.
Il farmaco è stato sviluppato da Tibotec, una della aziende farmaceutiche della Janssen, in collaborazione con Vertex e Mitsubishi Tanabe Pharma. Janssen detiene il diritto di commercializzazione in Europa, America Latina, Medio Oriente, Africa, India, Australia e Nuova Zelanda con il nome commerciale di INCIVO®; Vertex commercializza telaprevir in Nord America con il nome di INCIVEK™ (approvato dall’FDA statunitense nel maggio 2011 e dalla Health Canada ad Agosto 2011 per il trattamento dell’Epatite cronica C di genotipo 1, con malattia di fegato compensata); Mitsubishi Tanabe Pharma possiede i diritti per la vendita di telaprevir in Giappone e in alcuni Paesi dell’Estremo Oriente.
FONTE: quotidianosanità, salus.it
Con telaprevir stessa efficacia in metà tempo
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thelondonsuede
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Re: Con telaprevir stessa efficacia in metà tempo
Almeno sono stati veloci. 5 mesi e mezzo dalla analoga decisione della F&D Administration. Chissa perchè non hanno approvato anche l'analogo Boceprevir (più in la nel tempo c'è un terzo famaco ancora più promettente, il PSI-7977).
Ricordo a tutti che questa classe di farmaci, essendo smaltita dal sistema citocromo P450, interagisce con praticamente tutte le HAART e alcuni di queste in maniera piuttosto rilevante (es. il Sustiva). La stessa casa farmaceutica sta conducendo uno studio per la rideterminazione dei dosaggi per l'uso in contemporanea di Telaprevir e le principali HAART. La prima fase dovrebbe finire a giugno del 2012. Per adesso, si consiglia vivamente l'utilizzo con l'interruzione delle HAART.
Per approfondimenti:
http://lilanew.forumup.it/about6039-lilanew.html
Ricordo a tutti che questa classe di farmaci, essendo smaltita dal sistema citocromo P450, interagisce con praticamente tutte le HAART e alcuni di queste in maniera piuttosto rilevante (es. il Sustiva). La stessa casa farmaceutica sta conducendo uno studio per la rideterminazione dei dosaggi per l'uso in contemporanea di Telaprevir e le principali HAART. La prima fase dovrebbe finire a giugno del 2012. Per adesso, si consiglia vivamente l'utilizzo con l'interruzione delle HAART.
Per approfondimenti:
http://lilanew.forumup.it/about6039-lilanew.html
Re: Con telaprevir stessa efficacia in metà tempo
All'ICAAC sono stati presentati i risultati sull'Interazione farmacocinetica fra Telaprevir & Raltegravir in volontari sani e sulle Interazioni fra HAART e l'inibitore della proteasi dell'HCV BI-201335.skydrake ha scritto: La stessa casa farmaceutica sta conducendo uno studio per la rideterminazione dei dosaggi per l'uso in contemporanea di Telaprevir e le principali HAART. La prima fase dovrebbe finire a giugno del 2012. Per adesso, si consiglia vivamente l'utilizzo con l'interruzione delle HAART.
Poiché la questione dell'interazione fra antiretrovirali e nuovi farmaci contro l'HCV è proprio quello che sta frenando la somministrazione di questi nuovi farmaci nelle persone con coinfezione, vi suggerisco di controllare in Natap se dovessero essere postati ulteriori aggiornamenti portati al congresso di Chicago.
P.S. A me questa cosa dell'interruzione della HAART piace molto poco. Ma ora non ho il tempo di cercare l'articolo che ho letto di recente sui problemi che può dare interromperla. Appena lo trovo, vi aggiorno.
Re: Con telaprevir stessa efficacia in metà tempo
Tutto sommato sono fiducioso per l'assunzione contemporanea. Nella fase di riassorbimento le due terapie si rallentano a vicenda, quindi aumentando le concentrazioni e le emivite. Se da un lato questo può esasperare gli effetti collaterali delle rispettive terapie (io ad esempio ancora mal sopporto il Sustiva), dall'altro qui si tratta solo di rideterminare i dosaggi ottimali. Oppure, Dora, hai il sospetto di ulteriori effetti collaterali per eccessivo carico del sistema citocromo P450?Dora ha scritto:All'ICAAC sono stati presentati i risultati sull'Interazione farmacocinetica fra Telaprevir & Raltegravir in volontari sani e sulle Interazioni fra HAART e l'inibitore della proteasi dell'HCV BI-201335.skydrake ha scritto: La stessa casa farmaceutica sta conducendo uno studio per la rideterminazione dei dosaggi per l'uso in contemporanea di Telaprevir e le principali HAART. La prima fase dovrebbe finire a giugno del 2012. Per adesso, si consiglia vivamente l'utilizzo con l'interruzione delle HAART.
Poiché la questione dell'interazione fra antiretrovirali e nuovi farmaci contro l'HCV è proprio quello che sta frenando la somministrazione di questi nuovi farmaci nelle persone con coinfezione, vi suggerisco di controllare in Natap se dovessero essere postati ulteriori aggiornamenti portati al congresso di Chicago.
P.S. A me questa cosa dell'interruzione della HAART piace molto poco. Ma ora non ho il tempo di cercare l'articolo che ho letto di recente sui problemi che può dare interromperla. Appena lo trovo, vi aggiorno.
Re: Con telaprevir stessa efficacia in metà tempo
Scusa Skydrake, ho fatto confusione. Quel che avevo letto riguardava in generale l'interruzione della HAART in persone anche HCV+, che pare dannoso, perché peggiora la fibrosi epatica, indipendentemente dall'aumentare della viremia e dal diminuire dei CD4 e dall'aumento di problemi cardiaci, renali o epatici evidenziato dallo studio SMART (cfr. Treatment Interruption Spurs Fibrosis in HIV/HCV Coinfected People).skydrake ha scritto:Tutto sommato sono fiducioso per l'assunzione contemporanea. Nella fase di riassorbimento le due terapie si rallentano a vicenda, quindi aumentando le concentrazioni e le emivite. Se da un lato questo può esasperare gli effetti collaterali delle rispettive terapie (io ad esempio ancora mal sopporto il Sustiva), dall'altro qui si tratta solo di rideterminare i dosaggi ottimali. Oppure, Dora, hai il sospetto di ulteriori effetti collaterali per eccessivo carico del sistema citocromo P450?
Pensando anche al generale crollo dei bianchi che si può verificare durante il trattamento con interferone, ne ho dedotto che sia meglio non interrompere la HAART quando si affronta la terapia contro l'HCV. Ma è una deduzione mia, che vale meno di zero.
Re: Con telaprevir stessa efficacia in metà tempo
Il problema sussiste solo nella fase iniziale in quanto qui stiamo parlando di interrompere la HAART per eradicare l'HCV. Ovviamente, l'interruzione è un lusso che possono permettersi solo quelli che invece hanno un numero sufficiente di CD4, l'interferone li fa crollare (n.d.r lo ricordo agli altri, tu Dora saresti persino capace di disegnare la formula stechiometrica dell'interferone).Dora ha scritto: Quel che avevo letto riguardava in generale l'interruzione della HAART in persone anche HCV+, che pare dannoso, perché peggiora la fibrosi epatica
Riguardo alla co-terapia, ne ho parlato col mio infettologo. In effetti vi sono persone con casi talmente disperati (epatiti acute/cirrosi epatiche con coinfezioni HIV e CD4<50 con viremie di entrambi i virus alle stelle) che non possono permettersi il lusso di aspettare anni per la messa a punto di dosaggi ottimali, nè di fare una ma non l'altra.
Re: Con telaprevir stessa efficacia in metà tempo
La Vertex, produttrice del Telaprevir, ha rilasciato un'anticipazione della sperimentazione in fase II di una terapia anti HCV di sole 12 settimane, per i pazienti coinfetti sotto HAART (Atripla). I risultati sono eccezionali. Da notare l'uso del VX-222.
(attenzione l'articolo è tratto dal sito della casa farmaceutica).
http://investors.vrtx.com/releasedetail ... eID=621138
________________________
November 5, 2011
Interim Data from Phase 2 Study Showed 93% of People with Hepatitis C Who Received a Total of 12 Weeks of a Combination Regimen Including INCIVEK™ (telaprevir) and VX-222 (400mg) Achieved a Viral Cure (SVR)
- Vertex announces it intends to start a Phase 3 study to evaluate a 12-week regimen in treatment naive and relapser patients with genotype 1 hepatitis C -
SAN FRANCISCO--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced today interim results from ZENITH, an ongoing Phase 2 study designed to assess the safety, tolerability and efficacy of multiple 12- and 24-week response-guided treatment regimens with VX-222 (100mg or 400mg), its lead polymerase inhibitor in development, in combination with INCIVEK™ (telaprevir ) tablets, pegylated-interferon and ribavirin in people with genotype 1 chronic hepatitis C who were new to treatment. On the basis of the results announced today and previously announced data from other treatment arms of the ZENITH study, Vertex intends to start a Phase 3 study to evaluate a total treatment duration of 12 weeks with this four-drug regimen in treatment naïve and relapser patients with genotype 1 chronic hepatitis C.
Data from the four-drug treatment arms (C and D) of ZENITH were announced today and showed that, regardless of treatment duration, 90 percent of patients in the VX-222 (400mg) group had undetectable levels of hepatitis C virus in the blood 12 weeks after the end of treatment (sustained viral response 12, or SVR12). Fifty percent (15/30) of patients who received the combination regimen including VX-222 (400mg) were eligible for a total of 12 weeks of treatment and 93 percent (14/15) of them achieved a viral cure (sustained viral response, or SVR). For patients in the VX-222 (400mg) arm who received an additional 12 weeks of pegylated-interferon and ribavirin alone, 87 percent (13/15) had undetectable hepatitis C virus 12 weeks after treatment ended. Study results also showed that patients treated with the four-drug regimen experienced a rapid viral response; more than 85 percent had undetectable heptatitis C virus in the blood at week four of treatment. The most frequent adverse events (≥20 percent) observed in the four-drug treatment arms were fatigue, nausea, diarrhea, anemia, pruritis (itchiness), insomnia and rash. Interim data from ZENITH will be presented during a late-breaker poster session at The Liver Meeting®, the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), in San Francisco November 4-8, 2011.
"More than 85 percent of patients in the four-drug treatment arms of ZENITH had undetectable hepatitis C virus at week 4 and, regardless of treatment duration, 90 percent of them cleared the hepatitis C virus," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "Based on these interim results, Vertex began discussions with regulatory agencies about the regulatory path for this four-drug regimen, with the intent to initiate Phase 3 studies in a broad group of people with genotype 1 hepatitis C in the first quarter of 2012."
"The potential to achieve high viral cure rates with just 12 weeks of therapy is an exciting prospect for the future of treatment," said David R. Nelson, M.D., Professor of Medicine at the University of Florida College of Medicine, Director of the UF Clinical and Translational Science Institute and Principal Investigator of the trial.
Patients in Arms C and D of ZENITH were assigned to receive all four drugs for the first 12 weeks of treatment. People who had undetectable hepatitis C virus levels in the blood (HCV RNA) at weeks two and eight were eligible to stop all treatment at week 12. The remaining patients were assigned to receive pegylated-interferon and ribavirin alone for an additional 12 weeks for a total of 24 weeks of treatment. In this study, VX-222, INCIVEK and ribavirin were given twice daily (BID).
Arms A (n=18) and B (n=29) of ZENITH were designed to evaluate all-oral, two-drug combination regimens of VX-222 (100 mg or 400 mg) and INCIVEK (1,125 mg). There was significant initial antiviral activity in people who were treated with VX-222 (400 mg) and INCIVEK in Arms A and B. However, as previously announced, these treatment arms were discontinued due to a pre-defined stopping rule related to viral breakthrough.
Two additional treatment arms (E and F) were added to the study to evaluate a 12-week, three-drug, all-oral, interferon-free regimen of VX-222 (400 mg), INCIVEK and ribavirin. Arm E (n=23) is evaluating people with genotype 1b chronic hepatitis C and Arm F (n=23) is evaluating people with genotype 1a chronic hepatitis C. Vertex expects to provide end-of-treatment data from the all-oral arms of the study in early 2012.
[qui c'era una tabella che postata viene deformata. si prega di guardare il testo originale]
In ZENITH, the amount of hepatitis C virus in the blood was measured by the Roche COBAS® Taqman HCV test with a limit of quantification of <25 IU/mL).
The most frequent adverse events (≥20 percent) observed in the four-drug treatment arms (C and D) were fatigue, nausea, diarrhea, anemia, pruritis (itchiness), insomnia and rash. The majority of events were mild or moderate. Severe events observed in at least two patients were neutropenia, hypomagnesemia and anemia. Three people in each study arm discontinued treatment before week 12 and one person in each arm discontinued treatment between weeks 12 and 24 while they were receiving pegylated-interferon and ribavirin alone. No patient discontinued treatment due to gastrointestinal symptoms or viral breakthrough.
About ZENITH
ZENITH is an ongoing Phase 2 study that initially enrolled 106 people with genotype 1 chronic hepatitis C and began with four treatment arms designed to evaluate multiple response-guided treatment regimens with VX-222, Vertex's lead polymerase inhibitor in development, in combination with INCIVEK, Pegasys® (pegylated-interferon alfa-2a) and Copegus® (ribavirin), three medicines approved to treat hepatitis C. The primary endpoint of the study is safety and tolerability. The secondary endpoint is on-treatment antiviral activity and the proportion of people in each treatment arm who achieve a sustained viral response.
Updates on Vertex's Development Plans in Hepatitis C
Vertex has several studies planned and ongoing designed to evaluate a total of 12 weeks of treatment for people with genotype 1 chronic hepatitis C.
Four-drug "QUAD" Regimens
Based on the results from ZENITH announced today and previously announced data from other treatment arms of the ZENITH study, Vertex is in discussions with regulatory agencies about the regulatory path for the four-drug regimen, with the intent to start a Phase 3 study evaluating a total treatment duration of 12 weeks in people with genotype 1 chronic hepatitis C who are new to treatment or who relapsed after at least one prior course of treatment with pegylated-interferon and ribavirin alone.
Vertex is also in discussions with regulatory agencies regarding two additional studies designed to evaluate 24- and 48-week response-guided, four-drug regimens in patients who are new to treatment and also have cirrhosis (scarring of the liver) and, separately, those who have not responded (partial and null responders) to at least one prior course of treatment with pegylated-interferon and ribavirin alone.
Interferon-Free, 12-Week Regimens
Vertex expects to provide end-of-treatment data from the all-oral arms (E and F) of ZENITH study in early 2012. These study arms are evaluating a 12-week regimen of VX-222, INCIVEK and ribavirin. Dosing for all patients is expected to be complete in December 2011.
12-Week INCIVEK Combination Regimen for IL28B Patients
In October 2011, Vertex announced the start of the Phase 3b CONCISE study that is designed to evaluate 12 weeks of INCIVEK in combination with pegylated-interferon and ribavirin among people with genotype 1 chronic hepatitis C who have the ‘CC' variation near the IL28B gene.
About INCIVEK and VX-222
INCIVEK™ (telaprevir) tablets is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication. INCIVEK is the most prescribed direct-acting antiviral for the treatment of genotype 1 chronic hepatitis C and has been used to treat more than 17,000 people in the United States.
INCIVEK was approved by the U.S. Food and Drug Administration (FDA) in May 2011 and by Health Canada in August 2011 for people with genotype 1 chronic hepatitis C with compensated liver disease (some level of damage to the liver but the liver still functions), including cirrhosis (scarring of the liver). INCIVEK is approved for people who are new to treatment, and for people who were treated previously but who did not achieve a sustained viral response, or viral cure (relapsers, partial responders and null responders).
VX-222 is an oral medicine in development that is a non-nucleoside inhibitor of the HCV NS5B polymerase. VX-222 is currently being evaluated in combination with INCIVEK, pegylated-interferon and ribavirin in a Phase 2 study. Vertex has worldwide commercial rights for VX-222.
INCIVEK (750 mg) is given as two 375 mg tablets three times daily for 12 weeks in combination with pegylated-interferon and ribavirin. Each monthly package of INCIVEK contains four weekly boxes that include daily blister strips. After the first 12 weeks, all patients stop receiving INCIVEK and continue treatment with pegylated-interferon and ribavirin alone for an additional 12 weeks or 36 weeks of treatment. With INCIVEK combination therapy, more than 60 percent of people treated for the first time, as well as those who relapsed after previous therapy, are expected to complete all treatment in 24 weeks. All other patients receive a total of 48 weeks of treatment. A Phase 3 study evaluating twice-daily dosing of INCIVEK is ongoing.
Rash and anemia are the most serious side effects associated with INCIVEK, which led to treatment discontinuation in about 1 percent of people in clinical studies. The most common side effects reported with INCIVEK combination treatment include fatigue, itching, nausea, diarrhea, vomiting, anal or rectal problems, and taste changes.
Vertex developed telaprevir in collaboration with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America where it is being marketed under the brand name INCIVEK (in-SEE-veck). Through its affiliate, Janssen, Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. In September 2011, telaprevir was approved in the European Union and Switzerland. Telaprevir is known as INCIVO® in Europe. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries. In September 2011, telaprevir was approved in Japan and will be known as Telavic®.
IMPORTANT SAFETY INFORMATION
Indication
INCIVEK™ (telaprevir) is a prescription medicine used with the medicines peginterferon alfa and ribavirin to treat chronic (lasting a long time) hepatitis C genotype 1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatment. It is not known if INCIVEK is safe and effective in children under 18 years of age.
Important Safety Information
INCIVEK should always be taken in combination with peginterferon alfa and ribavirin. Ribavirin may cause birth defects or death of an unborn baby. Therefore, a patient should not take INCIVEK combination treatment if she is pregnant or may become pregnant, or if he is a man with a sexual partner who is pregnant. Patients must use two forms of effective birth control during treatment and for the 6 months after treatment with these medicines.
INCIVEK and other medicines can affect each other and can also cause side effects that can be serious or life threatening. There are certain medicines patients cannot take with INCIVEK combination treatment. Patients should tell their healthcare providers about all the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements.
INCIVEK can cause serious side effects including rash and anemia. The most common side effects of INCIVEK include itching, nausea, diarrhea, vomiting, anal or rectal problems, taste changes and tiredness. There are other possible side effects of INCIVEK, and side effects associated with peginterferon alfa and ribavirin also apply to INCIVEK combination treatment. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.
Please see full Prescribing Information for INCIVEK including the Medication Guide, available at http://www.INCIVEK.com.
INCIVEK™ is a trademark of Vertex Pharmaceuticals Incorporated.
PEGASYS® and COPEGUS® are registered trademarks of Hoffmann-La Roche.
About Hepatitis C
Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.1 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.1 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.1
Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.2 However, approximately 60 percent of people do not achieve SVR,3,4,5 or viral cure,6 after treatment with 48 weeks of pegylated-interferon and ribavirin alone. If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.7,8
More than 170 million people worldwide are chronically infected with hepatitis C.6 In the United States, nearly 4 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.9 Hepatitis C is four times more prevalent in the United States compared to HIV.9 The majority of people with hepatitis C in the United States were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.10 Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 4,600 to 12,000 deaths annually.11,12 By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.9
Special Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including statements regarding (i) the intent to initiate Phase 3 studies for the QUAD regimen in the first quarter of 2012; (ii) the potential to achieve high viral cure rates with just 12 weeks of therapy; (iii) Vertex's discussions with regulatory authorities regarding future clinical trials and (iv) end-of-treatment data from the all-oral arms of the ZENITH study. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the interim data presented in this press release may not be predictive of the final outcomes from this clinical trial; the outcomes from additional arms in this clinical trial and/or from any future clinical trials of telaprevir/VX-222 may not be favorable; future scientific, clinical, competitive or other market factors may adversely affect the potential for telaprevir/VX-222-based therapy and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through Vertex's website at http://www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
(attenzione l'articolo è tratto dal sito della casa farmaceutica).
http://investors.vrtx.com/releasedetail ... eID=621138
________________________
November 5, 2011
Interim Data from Phase 2 Study Showed 93% of People with Hepatitis C Who Received a Total of 12 Weeks of a Combination Regimen Including INCIVEK™ (telaprevir) and VX-222 (400mg) Achieved a Viral Cure (SVR)
- Vertex announces it intends to start a Phase 3 study to evaluate a 12-week regimen in treatment naive and relapser patients with genotype 1 hepatitis C -
SAN FRANCISCO--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced today interim results from ZENITH, an ongoing Phase 2 study designed to assess the safety, tolerability and efficacy of multiple 12- and 24-week response-guided treatment regimens with VX-222 (100mg or 400mg), its lead polymerase inhibitor in development, in combination with INCIVEK™ (telaprevir ) tablets, pegylated-interferon and ribavirin in people with genotype 1 chronic hepatitis C who were new to treatment. On the basis of the results announced today and previously announced data from other treatment arms of the ZENITH study, Vertex intends to start a Phase 3 study to evaluate a total treatment duration of 12 weeks with this four-drug regimen in treatment naïve and relapser patients with genotype 1 chronic hepatitis C.
Data from the four-drug treatment arms (C and D) of ZENITH were announced today and showed that, regardless of treatment duration, 90 percent of patients in the VX-222 (400mg) group had undetectable levels of hepatitis C virus in the blood 12 weeks after the end of treatment (sustained viral response 12, or SVR12). Fifty percent (15/30) of patients who received the combination regimen including VX-222 (400mg) were eligible for a total of 12 weeks of treatment and 93 percent (14/15) of them achieved a viral cure (sustained viral response, or SVR). For patients in the VX-222 (400mg) arm who received an additional 12 weeks of pegylated-interferon and ribavirin alone, 87 percent (13/15) had undetectable hepatitis C virus 12 weeks after treatment ended. Study results also showed that patients treated with the four-drug regimen experienced a rapid viral response; more than 85 percent had undetectable heptatitis C virus in the blood at week four of treatment. The most frequent adverse events (≥20 percent) observed in the four-drug treatment arms were fatigue, nausea, diarrhea, anemia, pruritis (itchiness), insomnia and rash. Interim data from ZENITH will be presented during a late-breaker poster session at The Liver Meeting®, the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), in San Francisco November 4-8, 2011.
"More than 85 percent of patients in the four-drug treatment arms of ZENITH had undetectable hepatitis C virus at week 4 and, regardless of treatment duration, 90 percent of them cleared the hepatitis C virus," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "Based on these interim results, Vertex began discussions with regulatory agencies about the regulatory path for this four-drug regimen, with the intent to initiate Phase 3 studies in a broad group of people with genotype 1 hepatitis C in the first quarter of 2012."
"The potential to achieve high viral cure rates with just 12 weeks of therapy is an exciting prospect for the future of treatment," said David R. Nelson, M.D., Professor of Medicine at the University of Florida College of Medicine, Director of the UF Clinical and Translational Science Institute and Principal Investigator of the trial.
Patients in Arms C and D of ZENITH were assigned to receive all four drugs for the first 12 weeks of treatment. People who had undetectable hepatitis C virus levels in the blood (HCV RNA) at weeks two and eight were eligible to stop all treatment at week 12. The remaining patients were assigned to receive pegylated-interferon and ribavirin alone for an additional 12 weeks for a total of 24 weeks of treatment. In this study, VX-222, INCIVEK and ribavirin were given twice daily (BID).
Arms A (n=18) and B (n=29) of ZENITH were designed to evaluate all-oral, two-drug combination regimens of VX-222 (100 mg or 400 mg) and INCIVEK (1,125 mg). There was significant initial antiviral activity in people who were treated with VX-222 (400 mg) and INCIVEK in Arms A and B. However, as previously announced, these treatment arms were discontinued due to a pre-defined stopping rule related to viral breakthrough.
Two additional treatment arms (E and F) were added to the study to evaluate a 12-week, three-drug, all-oral, interferon-free regimen of VX-222 (400 mg), INCIVEK and ribavirin. Arm E (n=23) is evaluating people with genotype 1b chronic hepatitis C and Arm F (n=23) is evaluating people with genotype 1a chronic hepatitis C. Vertex expects to provide end-of-treatment data from the all-oral arms of the study in early 2012.
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In ZENITH, the amount of hepatitis C virus in the blood was measured by the Roche COBAS® Taqman HCV test with a limit of quantification of <25 IU/mL).
The most frequent adverse events (≥20 percent) observed in the four-drug treatment arms (C and D) were fatigue, nausea, diarrhea, anemia, pruritis (itchiness), insomnia and rash. The majority of events were mild or moderate. Severe events observed in at least two patients were neutropenia, hypomagnesemia and anemia. Three people in each study arm discontinued treatment before week 12 and one person in each arm discontinued treatment between weeks 12 and 24 while they were receiving pegylated-interferon and ribavirin alone. No patient discontinued treatment due to gastrointestinal symptoms or viral breakthrough.
About ZENITH
ZENITH is an ongoing Phase 2 study that initially enrolled 106 people with genotype 1 chronic hepatitis C and began with four treatment arms designed to evaluate multiple response-guided treatment regimens with VX-222, Vertex's lead polymerase inhibitor in development, in combination with INCIVEK, Pegasys® (pegylated-interferon alfa-2a) and Copegus® (ribavirin), three medicines approved to treat hepatitis C. The primary endpoint of the study is safety and tolerability. The secondary endpoint is on-treatment antiviral activity and the proportion of people in each treatment arm who achieve a sustained viral response.
Updates on Vertex's Development Plans in Hepatitis C
Vertex has several studies planned and ongoing designed to evaluate a total of 12 weeks of treatment for people with genotype 1 chronic hepatitis C.
Four-drug "QUAD" Regimens
Based on the results from ZENITH announced today and previously announced data from other treatment arms of the ZENITH study, Vertex is in discussions with regulatory agencies about the regulatory path for the four-drug regimen, with the intent to start a Phase 3 study evaluating a total treatment duration of 12 weeks in people with genotype 1 chronic hepatitis C who are new to treatment or who relapsed after at least one prior course of treatment with pegylated-interferon and ribavirin alone.
Vertex is also in discussions with regulatory agencies regarding two additional studies designed to evaluate 24- and 48-week response-guided, four-drug regimens in patients who are new to treatment and also have cirrhosis (scarring of the liver) and, separately, those who have not responded (partial and null responders) to at least one prior course of treatment with pegylated-interferon and ribavirin alone.
Interferon-Free, 12-Week Regimens
Vertex expects to provide end-of-treatment data from the all-oral arms (E and F) of ZENITH study in early 2012. These study arms are evaluating a 12-week regimen of VX-222, INCIVEK and ribavirin. Dosing for all patients is expected to be complete in December 2011.
12-Week INCIVEK Combination Regimen for IL28B Patients
In October 2011, Vertex announced the start of the Phase 3b CONCISE study that is designed to evaluate 12 weeks of INCIVEK in combination with pegylated-interferon and ribavirin among people with genotype 1 chronic hepatitis C who have the ‘CC' variation near the IL28B gene.
About INCIVEK and VX-222
INCIVEK™ (telaprevir) tablets is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication. INCIVEK is the most prescribed direct-acting antiviral for the treatment of genotype 1 chronic hepatitis C and has been used to treat more than 17,000 people in the United States.
INCIVEK was approved by the U.S. Food and Drug Administration (FDA) in May 2011 and by Health Canada in August 2011 for people with genotype 1 chronic hepatitis C with compensated liver disease (some level of damage to the liver but the liver still functions), including cirrhosis (scarring of the liver). INCIVEK is approved for people who are new to treatment, and for people who were treated previously but who did not achieve a sustained viral response, or viral cure (relapsers, partial responders and null responders).
VX-222 is an oral medicine in development that is a non-nucleoside inhibitor of the HCV NS5B polymerase. VX-222 is currently being evaluated in combination with INCIVEK, pegylated-interferon and ribavirin in a Phase 2 study. Vertex has worldwide commercial rights for VX-222.
INCIVEK (750 mg) is given as two 375 mg tablets three times daily for 12 weeks in combination with pegylated-interferon and ribavirin. Each monthly package of INCIVEK contains four weekly boxes that include daily blister strips. After the first 12 weeks, all patients stop receiving INCIVEK and continue treatment with pegylated-interferon and ribavirin alone for an additional 12 weeks or 36 weeks of treatment. With INCIVEK combination therapy, more than 60 percent of people treated for the first time, as well as those who relapsed after previous therapy, are expected to complete all treatment in 24 weeks. All other patients receive a total of 48 weeks of treatment. A Phase 3 study evaluating twice-daily dosing of INCIVEK is ongoing.
Rash and anemia are the most serious side effects associated with INCIVEK, which led to treatment discontinuation in about 1 percent of people in clinical studies. The most common side effects reported with INCIVEK combination treatment include fatigue, itching, nausea, diarrhea, vomiting, anal or rectal problems, and taste changes.
Vertex developed telaprevir in collaboration with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America where it is being marketed under the brand name INCIVEK (in-SEE-veck). Through its affiliate, Janssen, Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. In September 2011, telaprevir was approved in the European Union and Switzerland. Telaprevir is known as INCIVO® in Europe. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries. In September 2011, telaprevir was approved in Japan and will be known as Telavic®.
IMPORTANT SAFETY INFORMATION
Indication
INCIVEK™ (telaprevir) is a prescription medicine used with the medicines peginterferon alfa and ribavirin to treat chronic (lasting a long time) hepatitis C genotype 1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatment. It is not known if INCIVEK is safe and effective in children under 18 years of age.
Important Safety Information
INCIVEK should always be taken in combination with peginterferon alfa and ribavirin. Ribavirin may cause birth defects or death of an unborn baby. Therefore, a patient should not take INCIVEK combination treatment if she is pregnant or may become pregnant, or if he is a man with a sexual partner who is pregnant. Patients must use two forms of effective birth control during treatment and for the 6 months after treatment with these medicines.
INCIVEK and other medicines can affect each other and can also cause side effects that can be serious or life threatening. There are certain medicines patients cannot take with INCIVEK combination treatment. Patients should tell their healthcare providers about all the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements.
INCIVEK can cause serious side effects including rash and anemia. The most common side effects of INCIVEK include itching, nausea, diarrhea, vomiting, anal or rectal problems, taste changes and tiredness. There are other possible side effects of INCIVEK, and side effects associated with peginterferon alfa and ribavirin also apply to INCIVEK combination treatment. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.
Please see full Prescribing Information for INCIVEK including the Medication Guide, available at http://www.INCIVEK.com.
INCIVEK™ is a trademark of Vertex Pharmaceuticals Incorporated.
PEGASYS® and COPEGUS® are registered trademarks of Hoffmann-La Roche.
About Hepatitis C
Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.1 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.1 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.1
Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.2 However, approximately 60 percent of people do not achieve SVR,3,4,5 or viral cure,6 after treatment with 48 weeks of pegylated-interferon and ribavirin alone. If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.7,8
More than 170 million people worldwide are chronically infected with hepatitis C.6 In the United States, nearly 4 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.9 Hepatitis C is four times more prevalent in the United States compared to HIV.9 The majority of people with hepatitis C in the United States were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.10 Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 4,600 to 12,000 deaths annually.11,12 By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.9
Special Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including statements regarding (i) the intent to initiate Phase 3 studies for the QUAD regimen in the first quarter of 2012; (ii) the potential to achieve high viral cure rates with just 12 weeks of therapy; (iii) Vertex's discussions with regulatory authorities regarding future clinical trials and (iv) end-of-treatment data from the all-oral arms of the ZENITH study. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the interim data presented in this press release may not be predictive of the final outcomes from this clinical trial; the outcomes from additional arms in this clinical trial and/or from any future clinical trials of telaprevir/VX-222 may not be favorable; future scientific, clinical, competitive or other market factors may adversely affect the potential for telaprevir/VX-222-based therapy and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through Vertex's website at http://www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
Re: Con telaprevir stessa efficacia in metà tempo
Altro breve rapporto riguardo l'uso del Telaprevir e il VX-222 assieme all'interferone e ribavirina nelle coinfezioni HCV-HIV.
Da notare che le percentuali riportate, pur rimanendo in termini assoluti molto buone, sono inferiori a quelle sbandierate nel report sul sito della Vertex
http://www.news-medical.net/news/201111 ... V-HCV.aspx
Da notare che le percentuali riportate, pur rimanendo in termini assoluti molto buone, sono inferiori a quelle sbandierate nel report sul sito della Vertex
http://www.news-medical.net/news/201111 ... V-HCV.aspx