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EASL TMC435 Hepatitis C Phase 2b ASPIRE Study Week 24 Interim Results

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EASL "TMC435" Hepatitis C Phase 2b ASPIRE Study Week 24 Interim Results

Medivir: Week 24 Interim Results From TMC435 Hepatitis C Phase 2b ASPIRE Study Presented at EASLHUDDINGE, Sweden, April 1, 2011 /PRNewswire-FirstCall/ --- Results Show Potent Antiviral Efficacy of Once Daily 150 mg TMC435 inHepatitis C Patients Who Have Failed Earlier Treatment, Especially in PriorNull Responders, and Excellent Safety and TolerabilityMedivir AB (OMX: MVIR), the emerging research-based specialtypharmaceutical company focused on infectious diseases, announces that theirpartner, Tibotec has presented the results of a planned Week 24 interimanalysis of the phase 2b ASPIRE study for TMC435 in treatment experiencedhepatitis C patients in a late-breaker session at the 46th Annual meeting ofthe

European Association for the Study of the Liver (EASL), Berlin, Germany.Treatment experienced patients are known to be the most difficult totreat hepatitis C patient group.TMC435 is a potent, once-daily, oral hepatitis C virus protease inhibitorwhich recently entered clinical phase 3 studies. The study enrolled patientschronically infected with genotype-1 hepatitis C virus (HCV) that hadpreviously failed treatment with standard of care therapy (peginterferon andribavarin). TMC435 is being jointly developed by Medivir and its partnerTibotec.In this Week 24 interim analysis, treatment-experienced patients whofailed peginterferon and ribavarin treatment achieved significantly greatervirologic response rates following treatment with TMC435-containing regimenat all doses, compared with placebo. Results demonstrated that the TMC435 150mg dose group showed the

highest response, particularly in prior nullresponders. In this 150 mg dose group, HCV RNA levels were undetectable atweek 24 for between 82% and 91% of the patients. Results also showed thatthere was no statistically relevant difference in safety and tolerabilitybetween the TMC435 and placebo treated groups.Ron Long, CEO of Medivir, commented: "We are delighted that these strongresults are to be presented at such a prestigious scientific conference asEASL. TMC435 continues to demonstrate why Medivir are so confident thathepatitis C treatment can be significantly changed by a more convenient, oncedaily protease inhibitor especially for treatment experienced patients. Thesedata and the recent start of phase 3 clinical studies for TMC435, representan exciting stage in Medivir's development as a significant player in theinfectious disease market."

On-treatment response rates are shown below.

TMC12/PR48 TMC24/PR48 TMC48/PR48 TMC12/PR48

100mg 100mg 100mg 150mg

(N=66) (N=65) (N=66) (N=66)

HCV RNA <25 IU/mL undetectable, % (u/N)

Overall population 67,7 (44/65) 59,4 (38/64) 53,8 (35/65) 63,1 (41/65)

Week 4 (RVR) *** *** *** ***

Prior null responders 33,3 (5/15) 50,0 (8/16) 25,0 (4/16) 35,3 (6/17)

Prior partial

responders 65,2 (15/23) 40,9 (9/22) 60,9 (14/23) 65,2 (15/23)

Prior relapser 88,9 (24/27) 80,8 (21/26) 65,4 (17/26) 80,0 (20/25)

Overall population 87,1 (54/62) 84,5 (49/58) 85,2 (52/61) 85,7 (54/63)

Week 24 *** *** *** ***

Prior null responders 71,4 (10/14) 83,3 (10/12) 68,8 (11/16) 70,6 (12/17)

Prior partial

responders 86,6 (19/22) 80,0 (16/20) 85,7 (18/21) 86,4 (19/22)

Prior relapser 96,2 (25/26) 88,5 (23/26) 95,8 (23/24) 95,8 (23/24)

*** Statistically significant difference versus placebo, p less then 0,001

(table continued)

TMC24/PR48 TMC48/PR48 Pbo48/PR48

150mg 150mg

(N=68) (N=65) (N=66)

HCV RNA <25 IU/mL undetectable, % (u/N)

Overall population 70,8 (46/65) 66,2 (43/65) 1,5 (1/65)

Week 4 (RVR) *** ***

Prior null responders 41,2 (7/17) 41,2 (7/17) 0,0 (0/16)

Prior partial responders 69,6 (16/23) 68,2 (15/22) 0,0 (0/23)

Prior relapser 92,0 (23/25) 80,8 (21/26) 3,8 (1/26)

Overall population 90,8 (59/65) 90,3 (56/62) 51,9 (28/54)

Week 24 *** ***

Prior null responders 81,3 (13/16) 93,3 (14/15) 44,4 (4/9)

Prior partial responders 90,9 (20/22) 86,4 (19/22) 19,0 (4/21)

Prior relapser 96,3 (26/27) 92,0 (23/25) 83,3 (20/24)

*** Statistically significant difference versus placebo, p less then 0,001

The ASPIRE study evaluates the effect of TMC435 in combination with standard of care (SoC) in 462 patients infected with the difficult to treat

genotype-1 hepatitis C virus who had undergone and failed prior treatmentwith (SoC). The study includes patients that have relapsed, achieved partialresponse, or achieved no response (null responders) to treatment withstandard of care. TMC435 was administered once daily at a dose of either 100mg or 150mg given for either 12, 24, or 48 weeks in combination with standardof care. Standard of care treatment was continued until the study completionat week 48.As well as the late-breaker ASPIRE data presented, a further threepresentations will be made at EASL on TMC435. These include:Oral presentation: Impact of IL28b genotype and pretreatment serum IP-10in treatment-naive genotype-1 HCV patients treated with TMC435 in combinationwith peginterferona-2a and ribavirin in PILLAR study, J. Aerssens, whichfound that during 24 weeks of treatment, IL28B genotype and serum IP-10 werepredictive of

response in patients receiving standard of care (peginterferonand ribavirin) but had limited predictive value in patients treated with bothTMC435 and peginterferon and ribavirin, therefore suggesting that TMC435, apotent, once daily oral protease inhibitor, may overcome the negativeconsequences of unfavourable host genotype encountered with pegIFN/RBV.Poster presentation No.472: Pharmacokinetics of TMC435 in subjects withmoderate hepatic impairment, V. Sekar, which found that no TMC435 doseadjustment was necessary for patients with moderate liver impairment.Poster presentation No.1221: Treatment outcome and resistance analysis inHCV genotype 1 patients previously exposed to TMC435 monotherapy andre-treated with TMC435 in combination with pegifna-2a/ribavirin, O. Lenz,which found that viral variants in patients who had received TMC435 as amonotherapy were no longer detected over time and successful

treatment afterprior exposure to TMC435 with emergence of resistance variants was possiblein 3/5 patients who had failed interferon-based therapy.About TMC435 in other clinical studiesTMC435 is a once-daily (q.d.) protease inhibitor drug jointly developedby Medivir and Tibotec Pharmaceuticals, to treat chronic hepatitis C virusinfections.Three clinical phase 3 response guided studies were recently initiated:- TMC435-C208 or QUEST-1 includes approximately 375 treatment-naivepatients- TMC435-C216 or QUEST-2 includes approximately 375 treatment-naivepatients- TMC435-C3007 or PROMISE includes approximately 375 who have relapsedafter prior interferon-based treatmentIn parallel to the recent start of the global phase 3-studies, TMC435 iscurrently in a follow up phase in three phase 2b clinical trials(TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naive and

in G1patients that failed previous IFN-based treatment. More safety and efficacydata from the phase 2b trials will be presented at scientific meetings laterin 2011.A phase 3 program for TMC435 has also recently been launched in Japan.For additional information for these studies, please seehttp://www.clinicaltrials.gov/About Hepatitis CHepatitis C is a blood-borne infectious disease of the liver and is aleading cause

of chronic liver disease and liver transplants. The WHOestimates that nearly 180 million people worldwide, or approximately 3% ofthe world's population, are infected with hepatitis C virus (HCV). The CDChas reported that almost three million people in the United States arechronically infected with HCV.About MedivirMedivir is an emerging research-based specialty pharmaceutical companyfocused on the development of high-value treatments for infectious diseases.Medivir has world class expertise in polymerase and protease drug targets anddrug development which has resulted in a strong infectious disease R & Dportfolio. The Company's key pipeline asset is TMC435, a protease inhibitorwhich has recently entered phase 3 clinical development for hepatitis C andis partnered with Tibotec Pharmaceuticals.Medivir is also marketing its first product, the unique cold sore

productXerese/Xerclear® which has recently been launched on the US market.Xerese/Xerclear®, which is also approved in Europe, is partnered withGlaxoKline to be sold OTC in Europe, Japan and Russia and with Meda ABin North America, Canada and Mexico. Medivir has retained the Rx rights forXerclear® in Sweden and Finland.For more information about Medivir, please visit the Company's website:http://www.medivir.com/.For more information about Medivir, please contact:

Medivir (http://www.medivir.com/):

Rein Piir, CFO & VP Investor Relations

Mobile: +46-708-537-292

Bertil sson, CFO Mobile: +46(70)576-13-50

M:Communications:

-Jane Elliott / Amber Bielecka / Katja Toon

Medivir@...

+44(0)20-7920 2330

USA: Roland Tomforde

+1-212-232-2356

http://Hepatitis Cnewdrugs.blogspot.com/2011/04/easl-tmc435-hepatitis-c-phase-2b-aspire.html

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