MDT Starts Phase-2 HCV Trial of Continuous Interferon Infusion
[The device used in this trial is the same one MDT sells for continuous infusion of insulin. Patients in the active arm of the trial will receive a continuous infusion of Intron-A (non-pegylated ifn alpha) and ribavirin dosed orally; patients in the control arm will receive the usual SoC consisting of injected Pegintron and oral ribavirin. This trial is open-label—there is no sham infusion for patients in the control arm nor a sham injection for the patients in the experimental arm.]
›Medtronic Initiates Phase II Hepatitis C Clinical Study ''COPE-HCV'' to Determine Tolerability and Safety of Continuous Interferon Infusion for Patients with HCV
Medtronic Paradigm® Pump Infusion System and CareLink™ Clinical Monitoring System Used to Study the Continuous Delivery of INTRON A in Previously Untreated Genotype 1 Patients
Wednesday September 2, 2009, 11:30 am EDT
MINNEAPOLIS--(BUSINESS WIRE)--Medtronic, Inc. (NYSE: MDT ), today reported the initiation and first enrollments of patients in COPE-HCV (COntinuous Interferon Delivery via the Medtronic Paradigm Pump Infusion System Clinical Evaluation for Chronic HCV), the company’s first-ever clinical study using an external pump infusion system to treat patients with the hepatitis C virus (HCV). The COPE-HCV trial is being conducted under an Investigational New Drug Application (IND).
COPE-HCV is a Phase II, 250-plus patient study designed to gather clinical data on the tolerability, safety and efficacy associated with continuous subcutaneous interferon infusion compared with the current standard-of-care in patients with HCV genotype 1 infection not previously treated. In the first month of the U.S. study, 20 patients have been enrolled at six clinical sites in Nashville, Minneapolis, Atlanta, San Antonio, and Sarasota, Fla. Stage 1 of this randomized controlled study will include 124 patients at up to 30 sites.
“For years Medtronic has developed drug-delivery systems to bypass traditional but less effective routes of administration and to help patients with chronic diseases better manage their conditions,” said Bill Hawkins, Medtronic chairman and CEO. “With this trial now underway, we have the potential to extend our pump technologies and develop yet another drug-delivery option for a chronic disease that impacts millions of lives. If successful, this novel therapy will open new doors to treating other advanced diseases more safely and effectively than currently available approaches.”
The World Health Organization has estimated that three to four million people become infected by HCV each year and 70 percent of those infected will develop chronic hepatitis. Standard-of-care for HCV is weekly injections of pegylated interferon in combination with oral ribavirin medication for up to 48 weeks. This therapy is only effective in treating approximately 43 percent of all genotype 1 patients, who represent the overwhelming majority of U.S. hepatitis C cases. In addition, many patients develop serious side effects from weekly injections, including chronic fatigue, depression, blood disorders, and flu-like symptoms.
“There are a host of challenges related to the treatment of HCV that, to this point, have resulted in less than optimal outcomes and therefore patients are at a greater risk for developing progressive liver disease,” said Dr. John McHutchison, associate director of the Duke Clinical University Research Institute (DCRI) and lead investigator of the Medtronic-sponsored study. “However, the innovative strategy that will be studied in the COPE HCV study may ultimately be shown to improve both efficacy and tolerability over currently available drug formulations.”
The COPE-HCV study uses the Medtronic Paradigm Infusion System, a device currently approved by the U.S. Food and Drug Administration for delivering insulin in patients with diabetes. It also incorporates the use of Medtronic’s CareLink remote data management system to ensure patients enrolled in the study are compliant to study protocol for the trial period. The COPE-HCV study will deliver INTRON® A, via the Paradigm pump in combination with oral REBETOL[ribavirin]. The comparison group in the study will use PegIntron™ and REBETOL. All drugs in the trial are manufactured and marketed by Schering-Plough.
About Medtronic Drug-Device Delivery Innovations
A pioneer of drug delivery systems, Medtronic recently announced new developments in its long-standing goal to create a “closed-loop” diabetes management system designed to closely mimic the insulin delivery of a normal pancreas. In addition, the company provides its SynchroMed® II implantable, drug infusion system for the treatment of chronic, intractable pain, or to deliver ITB TherapySM (Intrathecal Baclofen Therapy) to treat severe spasticity related to brain injury, cerebral palsy, multiple sclerosis, spinal cord injury, or stroke.‹
[Updated entries for Locteron, ACH-1095, and IMO-2125.]
The following paragraphs are in descending order of likelihood of success. There is no claim of completeness here; i.e. paragraphs 3-6 do not necessarily mention all of the applicable drug candidates within the grouping. Please see #msg-36688204 for the semantics of the terms nucleoside and nucleotide.
1. The two leading protease inhibitors: Telaprevir (VRTX/JNJ; phase-3) and Boceprevir (MRK; phase-3). The Telaprevir program is further advanced, so let’s call Telaprevir and Boceprevir 1a and 1b, respectively. Both drugs have shown very impressive efficacy in phase-2 trials, although neither has a completely clean safety profile (see references below).
Telaprevir in the treatment-naïve setting: phase-3 program: #msg-27623529 (ADVANCE study), #msg-26228377 (both studies); phase-2b program: #msg-29019931 (PROVE-1/2 trials made simple), #msg-28746843 (PROVE-1/2 detailed results); C208 study of BID vs TID dosing: #msg-33270634.
Telaprevir in the second-line setting: phase-3 program (REALIZE study): #msg-32901932; phase-2 program: #msg-37316151 (PROVE-3 study), #msg-28749322 (‘107’ open-label extension for PROVE-1/2 failures).
Boceprevir in the treatment-naïve setting: phase-3 program (SPRINT-2 and RESPOND-2): #msg-29474929; phase-2b program: #msg-37298987, #msg-37298085 (SPRINT-1 results from EASL 2009); #msg-31190433 (musings on interim results).
Boceprevir in the second-line setting: phase-3 (RESPOND-2) study: #msg-29474929.
2. ITMN-191 (a/k/a/ RG7227) and RG7128 (f/k/a/ R7128), the two oral drugs that Roche is testing in the INFORM-1 study that does not include interferon or ribavirin: #msg-37309589 (data reported at EASL 2009); #msg-37312942 (VL chart with annotations by ghmm); #msg-37208214 (PR on expanded trial design), #msg-37209844 (clinicaltrials.gov listing), #msg-36388140 (EASL 2009 abstract), #msg-36455893 (musings by tony111 and ghmm).
RG7128 (VRUS/Roche; phase-2b) is a nucleoside polymerase inhibitor: #msg-34746768.
Although ITMN-191 and RG7128 are not necessarily the best drugs in their respective classes, the fact that Roche is testing them in INFORM-1 gives them a leg up on competing drugs at the same stage of development, IMO.
3. Agents in phase-2b, phase-3 or later that use an established MoA: Albuferon (HGSI/NVS; BLA submission pending): #msg-36140577 (phase-3 data), #msg-36254180 (lack of SPA!), #msg-34770426 (new trial with monthly dosing); BI201335 (B-I; phase-2b), a protease inhibitor: #msg-33564560, #msg-34774813; and Locteron (Biolex; phase-2b), a long-acting interferon made in transgenic plants that may qualify for the 505b2 approval pathway: #msg-37298340 (phase-2a data from EASL 2009), #msg-37178496 (phase-2b design), #msg-40953698 (manufacturing agreement).
4. Agents in phase-1b or phase-2a that use an established MoA. These include TMC435 (Medivir/JNJ; phase-2), a protease inhibitor: #msg-37298740; SCH 900518 (MRK, phase-2a), a protease inhibitor (follow-up to Boceprevir): #msg-34338549, #msg-34774813; GS-9190 (GILD; phase-2), a non-nucleoside polymerase inhibitor: #msg-32919311; IDX184 (IDIX; phase-1b), a nucleotide polymerase-inhibitor: #msg-36392616 (EASL 2009 abstract), #msg-34763865 (PR for trial commencement), #msg-26915921 (how IDX184 is better than NM283); PSI-7851 (VRUS, phase-1b), a nucleotide polymerase inhibitor: #msg-40115833; IFN-alpha-XL (FLML; phase-1b): #msg-28837983; ABT-450 (ABT/Enanta, phase-1), a protease inhibitor: #msg-35708745; VCH-222 (VRTX, phase-1b), a non-nucleoside “thumb” polymerase inhibitors that VRTX acquired from ViroChem (VCH-759 is a backup): #msg-37089807; IFN-Lambda (BMY/ZGEN; phase-1b): #msg-34768182 (BMY partnership), #msg-37277825 (interim phase-1b data); MK-7009 (MRK, phase-2a), a protease inhibitor: #msg-34337398, #msg-34335327; and ANA598 (ANDS, entering phase-2), a non-nucleoside “palm” polymerase inhibitor that caused severe rash in phase-1 monotherapy (#msg-40064675).
5. Very-early-stage compounds that use an established MoA. These include ACH-1625 (ACHN;phase-1), a protease inhibitor: #msg-39146155; IDX375 (IDIX, preclinical), a non-nucleoside “palm” polymerase inhibitor: #msg-34334563, #msg-31043481; MK-3281 (MRK, phase-1), a non-nucleoside “thumb” polymerase inhibitor: #msg-36508769; PSI-938 (VRUS, preclinical), a purine-analog nucleoside polymerase inhibitor: #msg-39322313; ‘hyperglycosylated’ interferon (Alios BioPharma, preclinical): #msg-35612425; IDX136/IDX316 (IDIX, preclinical), two closely related macrocyclic protease inhibitors of which IDIX will select one to advance into phase-1: #msg-37246670 (EASL 2009 PR), #msg-37315636 (EASL 2009 poster); BMS-650032 (BMY, phase-1b), a protease/NS3 inhibitor: #msg-40361108; and VX-813/VX-985 (VRTX, phase-1/preclinical), protease inhibitors from VRTX being developed as follow-on compounds to Telaprevir: #msg-36022752.
6. Agents in phase-2 or earlier that use a novel MoA. These include CF-102 (Can-Fite, phase-1/2), a polymerase inhibitor that purportedly induces apoptosis: #msg-39588570; BMS-790052 (BMY, phase-2), an NS5A inhibitor: #msg-40350075, #msg-33270670; MB11362 (Roche/MBRX, preclinical), MoA undisclosed: #msg-38456136; A-831 (AZN, status unknown), an NS5A inhibitor: #msg-16682361; a preclinical NS5A program that GSK acquired from GNLB: #msg-33209281, #msg-33211420; IL-7 (Cytheris, phase-1/2) an injectable immunomodulator: #msg-33152073; Debio 025 (Debiopharm, phase-2a), a cyclophilin inhibitor: #msg-37359213; NIM811 (NVS, status unknown), a cyclophilin inhibitor: #msg-36507550; GI-5005 (GlobeImmune, phase-2), an injectable immunomodulator: #msg-37298510; ACH-1095 (ACHN, preclinical), an NS4A inhibitor that GILD dropped while retaining the right to opt back in: #msg-41217537; an unnamed NS5A inhibitor that VRTX acquired from ViroChem (preclinical): #msg-36022752; an unnamed NS5A inhibitor from Presidio Pharma (status unknown): #msg-27791536; clemizole (Stanford University, preclinical), an NS4B inhibitor: #msg-39883747; nitazoxanide (Romark/Chugai, phase-2): #msg-35738696; ITX5061 (iTherX, phase-2a), MoA unknown: #msg-35319690; IMO-2125 (IDRA, preclinical), a TLR9 agonist: #msg-38860625; and an unnamed entry inhibitor from PGNX (preclinical): #msg-38519885.
7. Miscellaneous programs that are nominally alive but not receiving any financial support. These include ANA773 (ANDS, phase-1), an oral TLR7 modulator that ANDS discontinued in Jun 2009 and is nominally available for partnering: #msg-38418158; and taribavirin (VRX, phase-2b), a “legacy” prodrug of ribavirin that has been floating around for a long time: #msg-38280961 (musings on final phase-2b data), #msg-37299101 (detailed 60-week data). (VRX, under a different name, is the inventor of ribavirin.)
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