Delving into the Latest Updates on Peginterferon alfa-2a/Ribavirin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug, Interferons

Synonyms

Pegasys Copegus Combination Pack

Target

IFNAR x IMPDH x RNAP x RNGTT

Action

agonists, inhibitors, modulators,

+ [1]

Mechanism

IFNAR agonists(Interferon alpha/beta receptor agonists), IMPDH inhibitors(Inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitors), RNAP inhibitors(Bacterial DNA-directed RNA polymerase inhibitors)

+ [3]

Therapeutic Areas

Infectious DiseasesDigestive System Disorders

Active Indication

Hepatitis C, Chronic

Inactive Indication

Fibrosis, LiverLiver Cirrhosis

Originator Organization

Hoffmann-La Roche, Inc.

Active Organization

Hoffmann-La Roche, Inc.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

United States (04 Jun 2004),

Hepatitis C, Chronic

Regulation-

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Structure/Sequence

Molecular FormulaC8H12N4O5

InChIKeyIWUCXVSUMQZMFG-AFCXAGJDSA-N

CAS Registry36791-04-5

Sequence Code 32821

The sequence is quoted from: *****

Author: Marc Bourlière ; Janice K. Albrecht ; Morris Sherman ; John A. Howe ; Ira Jacobson ; Richard O. Barnard ; Margaret H. Burroughs ; John M. Vierling ; Heather L. Sings ; Lisa D. Pedicone ; Venkata Goteti ; Eric Lawitz ; Fred Poordad ; Claus Niederau ; Christophe Hezode ; Clifford A. Brass ; Bruce R. Bacon ; Steven L. Flamm

BACKGROUND & AIMSThe addition of boceprevir to therapy with peginterferon alfa-2b and ribavirin results in significantly higher rates of sustained virologic response (SVR) in previously treated patients with chronic hepatitis C virus (HCV) genotype-1 infection, compared with peginterferon alfa-2b and ribavirin alone. We assessed SVR with boceprevir plus peginterferon alfa-2a-ribavirin (PEG2a/R) in patients with identical study entry criteria.METHODSIn a double-blind, placebo-controlled trial, 201 patients with HCV genotype-1 who had relapsed or not responded to previous therapy were assigned to groups (1:2) and given a 4-week lead-in phase of PEG2a/R, followed by placebo plus PEG2a/R for 44 weeks (PEG2a/R) or boceprevir plus PEG2a/R for 44 weeks (BOC/PEG2a/R). The primary end point was SVR 24 weeks after therapy ended.RESULTSThe addition of boceprevir after 4 weeks of lead-in therapy with PEG2a/R significantly increased the rate of SVR from 21% in the PEG2a/R group to 64% in the BOC/PEG2a/R group (P < .0001). Among patients with poor response to interferon therapy (<1-log(10) decline in HCV RNA at week 4), 39% in the BOC/PEG2a/R group had SVRs, compared with none of the patients in the PEG2a/R group. Among patients with good response to interferon (≥1-log(10) decline), 71% in the BOC/PEG2a/R group had SVRs, compared with 25% in the PEG2a/R group. A ≥1-log(10) decline in HCV RNA at treatment week 4 was the strongest independent predictor of SVR, exceeding that of IL-28B genotype. Among 8 patients who began the study with HCV amino acid variants associated with boceprevir resistance, 3 (38%) achieved SVRs. Fifty percent of patients in the BOC/PEG2a/R group developed anemia (hemoglobin <10.0 g/dL), compared with 27% in the PEG2a/R group; 43% vs 21%, respectively, developed neutropenia (neutrophil count <750/mm(3)).CONCLUSIONSThe addition of boceprevir after 4 weeks of lead-in therapy with PEG2a/R caused significantly higher rates of SVR in previously treated patients with chronic HCV genotype-1 infection, compared with patients given only PEG2a/R. ClinicalTrials.gov Identifier: NCT00845065.

01 Jan 2011·Bioorganic & Medicinal Chemistry LettersQ4 · MEDICINE

Quinolones as HCV NS5B polymerase inhibitors

Q4 · MEDICINE

Article

Author: Nhat To ; Wendy B. Young ; Tony L. Ton ; Ken A. Brameld ; Michael J. Green ; Yu M. Xia ; Isabelle Lehoux ; Michael B. Shaghafi ; James W. Janc ; Huiyong Hu ; Roopa Rai ; Dange V. Kumar ; Ravi Rajagopalan ; John R. Somoza

Hepatitis C virus (HCV) infection is treated with a combination of peginterferon alfa-2a/b and ribavirin. To address the limitations of this therapy, numerous small molecule agents are in development, which act by directly affecting key steps in the viral life-cycle. Herein we describe our discovery of quinolone derivatives, novel small-molecules that inhibit NS5b polymerase, a key enzyme of the viral life-cycle. A crystal structure of a quinoline analog bound to NS5B reveals that this class of compounds binds to allosteric site-II (non-nucleoside inhibitor-site 2, NNI-2) of this protein.

01 Jan 2010·The Korean Journal of Hepatology

New treatments for chronic hepatitis C

Review

Author: Chung, Raymond T. ; Jang, Jae Young

Treatments for chronic hepatitis C has evolved significantly in the past 15 years. The standard of care (SOC) is peginterferon alfa-2a/-2b with ribavirin for 48 weeks or 24 weeks in patients infected with HCV genotype 1 or 2/3, respectively. The treatment duration can be individualized based on the baseline viral load and the speed of the virologic response during treatment. However, current therapies are associated with side effects, complications, and poor patient tolerability. Therefore, there is an urgent need to identify better strategies for treating this disease. An improved sustained virologic response (SVR) can be achieved with new HCV-specific inhibitors against NS3/4A and NS5B polymerases. Recent trials have found SVR rates in patients with HCV genotype 1 infection of 61~68% and 67~75% for combining the SOC with the protease inhibitors telaprevir and boceprevir, respectively. Several new HCV-specific inhibitors such as protease inhibitors and nucleoside and non-nucleoside polymerase inhibitors as well as non-HCV-specific compounds with anti-HCV activity are currently in clinical evaluation. In this review we discuss these new treatments for chronic hepatitis C.

100 Deals associated with Peginterferon alfa-2a/Ribavirin

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R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hepatitis C, Chronic	United States	Hoffmann-La Roche, Inc.	04 Jun 2004

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Fibrosis, Liver	Phase 2	United States	Hoffmann-La Roche, Inc.	01 Jun 2000
Liver Cirrhosis	Phase 2	United States	Hoffmann-La Roche, Inc.	01 Jun 2000

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00100659 (Peds-C, CTgov)	Phase 3	Hepatitis C, Chronic	114	Pegylated Interferon/ribavirin (Pegylated Interferon/Ribavirin)	cchwtroogx(sxdxeajwkk) = lgcqymkqmv memlyemakk (uxnhcoqxal, rsvsfazryh - kqpgwsagfw) View more	-	01 Jul 2013
				Pegylated Interferon/ribavirin (Pegylated Interferon/Placebo)	cchwtroogx(sxdxeajwkk) = btdbljazzd memlyemakk (uxnhcoqxal, lvgajfbfnv - qnuinnwvwf) View more
NCT00561015 (CTgov)	Phase 2	Chronic hepatitis C genotype 3	52	Peg-IFN-alfa-2a + Ribavirin (Standard Treatment)+Telaprevir (TVR Then Peg-IFN-alfa-2a + RBV (T2 & PR24) - Genotype 2)	loctesptlz(xyaopksnjv) = gxdgdxhknw ustfrrlpve (iuvrxiivbl, xaasdueajl - ylufnviyka) View more	-	04 Jun 2013
				Peg-IFN-alfa-2a + Ribavirin (Standard Treatment)+Telaprevir (TVR With Peg-IFN-alfa-2a + RBV (T2/PR24) - Genotype 2)	loctesptlz(xyaopksnjv) = hcnkwcrpge ustfrrlpve (iuvrxiivbl, pmltjwdnie - tiiwxkhciu) View more
IAS2012	Not Applicable	HIV Infections \| Hepatitis C	100	Peginterferon/Ribavirin + Boceprevir	mmbyvycctu(ukfcdxfvqx) = Decreases were observed in CD4 counts, consistent with interferon treatment, and were similar in both treatment groups vhfvykqnmn (xmklrvkzrk )	-	01 Jan 2012
				Peginterferon/Ribavirin
NCT00495131 (CTgov)	Phase 4	Chronic hepatitis C genotype 1	308	Pegylated interferon alfa-2a plus ribavirin	(wihkdusbua) = dzpahcbjnp lguokvpzhi (yphrckmwqw, jqlcexnywn - satrgkygpm) View more	-	07 Sep 2009
APRICOT (IAS2005)	Not Applicable	Hepatitis C	860	PEGASYS 180µg/wk plus COPEGUS 800mg/day	(pdjrorntcd) = hsssoggpup uvvybvfjgf (lktqlsumsl )	-	01 Jan 2005
APRICOT study (IAS2004)	Not Applicable	Coinfection	289	PEGASYS plus COPEGUS	(glicwmhdby): OR = 3.56 (95% CI, 2.0 - 6.36)	-	01 Jan 2004
				PEGASYS monotherapy

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Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

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