Shorter treatment course potentially on the horizon for Hepatitis C patients
April 15, 2016
Press Releases
Investigational treatment, RG-101 combined with direct-acting antivirals shows potential to be effective in Hepatitis C with a ‘shorter than standard’ four week course
April 15, 2016, Barcelona, Spain: Data from a Phase 2 clinical trial show that an investigational injectable treatment known as RG-101 in combination with a four week course of oral direct-acting antiviral (DAA) treatment was well tolerated and resulted in high virologic response rates post-treatment among Hepatitis C (HCV) infected patients with genotypes 1 and 4, who had not been treated previously. The findings, presented today at The International Liver Congress™ 2016 in Barcelona, Spain are an interim analysis, with ongoing research to assess virologic response over a 48 week follow-up period to further assess the safety and efficacy of a four week treatment course.
The investigational treatment, RG-101 works on microRNA-122, which the virus uses to replicate. Drugs that interfere with miR-122 could inhibit HCV replication, acting earlier in the viral lifecycle than currently approved HCV protease, polymerase or NS5A inhibitors.1 The current standard of care treatment in HCV consists of eight-12 weeks of DAA oral agents.2
“These early results indicate the potential for RG-101 with oral DAA combination therapy to provide an effective Hepatitis C regimen for patients with a short treatment course of just four weeks,” said Dr Mihaly Makara from the Buda Hepatology Centre, Budapest, Hungary, and lead study author. “We very much hope the long-term, 48-week follow-up data follows the same trend.”
This international study enrolled 79 patients with chronic HCV, genotype 1 or 4 who had not previously received treatment. Each patient received a 2mg/kg injection of RG-101 on Day one, with a four week course of oral DAAs (either ledipasvir/sofosbuvir, simeprevir, or daclatasvir), following by a second 2mg/kg injection of RG-101 on Day 29. The mean baseline viral load among patients was 5.805 (log10) IU/mL.
Interim analysis showed that 97.4% (37/38) and 100% (14/14) of patients at eight and 12 weeks respectiviely had a high virologic response. This was determined by assessing HCV levels ‘below the lower limit of quantification’ (<12 IU/mL), using the Abbot RealTimeHCV Assay, a consolidated HCV viral load and HCV genotype testing method.3
The combination therapy was generally well tolerated, with the majority of side effects reported being mild in nature, including headache and fatigue, reported in 11.4% of patients.
“It is encouraging to see a potential treatment combination on the horizon that could limit treatment duration for patients,” said Professor Tom Hemming Karlsen, EASL Vice Secretary. “We will be eagerly awaiting the 48 week follow-up data.”
Regulus Press Release
April 15, 2016
Regulus Presents Additional Interim Data on RG-101 at International Liver Congress™ (ILC 2016)
- Continued High Virologic Response Rates across All Treatment Arms Out through 24 weeks of Follow Up -
- Data Supports RG-101's Potential to Reduce Treatment Regimen to 4 Weeks -
- Conference Call at 8AM EDT (2PM CEST) Today -
Today, Regulus reported longer-term follow up results across all arms of the ongoing study:
Follow-Up After 2nd
Dose of RG-101 |
RG-101 +
Harvoni®
|
RG-101 +
Olysio®
|
RG-101 +
Daklinza™
|
Week 8
|
21/21 (100%)
|
21/21 (100%)
|
20/22* (90.9%)
|
Week 12
|
14/14 (100%)
|
14/15* (93.3%)
|
12/12 (100%)
|
Week 16
|
9/9 (100%)
|
8/9* (88.9%)
|
9/9 (100%)
|
Week 20
|
2/2 (100%)
|
2/2 (100%)
|
2/2 (100%)
|
Week 24
|
1/1 (100%)
|
2/2 (100%)
|
-- (--)
|
Response defined as HCV RNA viral load below LLOQ using RealTime HCV Assay (Abbott) with LLOQ = 12
*Includes one relapse patient in the Olysio arm (week 12) and one relapse patient in the Daklinza arm (week 8)
"We believe the data reported at the ILC meeting further demonstrate the clinical utility of RG-101 to shorten oral HCV treatment regimens to just four weeks," said Paul Grint , M.D., President and CEO of Regulus. "With interim data now through 24 weeks of follow-up, the consistent trend in efficacy and safety is encouraging, which supports the potential of RG-101 to become a backbone agent in combination with all classes of oral therapies. Throughout the year, we look forward to obtaining more data from multiple studies across our broad Phase 2 development program."
To date, RG-101 has been generally well tolerated with the majority of adverse events considered mild or moderate, and with no study discontinuations. Changes in pharmacodynamic markers are indicative of effective target engagement and consistent with the company's prior experience with miR-122 inhibition. The primary endpoint analysis (12 week follow up) for all 79 patients in the study is anticipated to be reported in late Q2 2016.
The investigator slides presented at the ILC 2016 meeting are available on the investor relations page of Regulus' website at www.regulusrx.com.
Conference Call & Webcast Information
Today at 8:00 a.m. EDT , Regulus will host a conference call and webcast to discuss the ILC 2016 interim results. A live webcast of the call will be available online at www.regulusrx.com. To access the call, please dial (877) 257-8599 (domestic) or (970) 315-0459 (international) and refer to conference ID 89822720. To access the telephone replay of the call, dial (855) 859-2056 (domestic) or (404) 537-3406 (international), passcode 89822720. The webcast and telephone replay will be archived on the company's website following the call.
About Hepatitis C Virus Infection (HCV)
Hepatitis C is a result of a hepatocyte specific infection induced by the virus known as HCV. Chronic HCV may lead to significant liver disease, including chronic active hepatitis, cirrhosis, and hepatocellular carcinoma. Up to 185 million people are chronically infected with HCV worldwide, and more than 500,000 people die from HCV annually. The CDC estimates that there are currently approximately 3.5 million persons infected with HCV in the United States. HCV shows significant genetic variation in worldwide populations due to its frequent rates of mutation and rapid evolution. There are six genotypes of HCV, with several subtypes within each genotype, which vary in prevalence across the different regions of the world. The response to treatment varies from individual to individual underscoring the inadequacy of existing therapies and highlights the need for combination therapies that not only target the virus but endogenous host factors as well, such as microRNA-122 (miR-122). Regulus believes that its miR-122 antagonist, RG-101, may be a useful agent in emerging combination regimens to address difficult-to-treat genotypes and to potentially expand upon the current therapies available to clinicians treating HCV patients.
About RG-101 for HCV
RG-101 is Regulus' wholly-owned, GalNAc-conjugated anti-miR targeting miR-122, which the HCV virus uses to replicate. Therapies that interfere with miR-122 could inhibit viral replication, acting earlier in the viral life cycle than currently approved oral agents. In a completed Phase I human proof-of-concept study, Regulus demonstrated that treatment with a single subcutaneous dose of RG-101 as monotherapy resulted in significant and sustained viral load reductions in all treated HCV patients, including patients with difficult to treat genotypes, various liver fibrosis status and those who have experienced viral relapse after a prior IFN-containing regimen.
Regulus has reported favorable interim data from an ongoing Phase II study evaluating the combination of RG-101 with multiple approved DAAs positioning RG-101 for both front-line and second-line commercial opportunities. Patients received a single subcutaneous injection of 2 mg/kg of RG-101 on Day 1, followed by 28 days of a once daily oral DAA (Harvoni®, Olysio®, or Daklinza™), followed by an additional subcutaneous injection of 2 mg/kg of RG-101 on Day 29. Regulus is planning to report primary endpoint results at 12 weeks following conclusion of treatment in late Q2 2016.
In collaboration with GSK, Regulus recently initiated a Phase II study evaluating the combination of RG-101 and GSK2878175, a non-nucleoside NS5B polymerase inhibitor, in treatment-naïve patients chronically infected with HCV genotypes 1 and 3. Additionally, enrollment is nearly complete in a multi-center, open label, non-randomized Phase I study to compare the safety, tolerability, pharmacokinetics, and pharmacodynamics of 2 mg/kg of RG-101 in subjects with severe renal insufficiency or end-stage renal disease (ESRD) to healthy control subjects, and further explore RG-101 in hepatitis C infected subjects with severe renal insufficiency or ESRD. Regulus anticipates reporting safety and efficacy data from the HCV/severe renal impairment or ESRD arm in the second half of 2016.
About microRNAs
The discovery of microRNAs in humans during the last decade is one of the most exciting scientific breakthroughs in recent history. microRNAs are small RNA molecules, typically 20 to 25 nucleotides in length, that do not encode proteins but instead regulate gene expression. More than 800 microRNAs have been identified in the human genome, and over two-thirds of all human genes are believed to be regulated by microRNAs. A single microRNA can regulate entire networks of genes. As such, these molecules are considered master regulators of the human genome. microRNA expression, or function, has been shown to be significantly altered or dysregulated in many disease states, including oncology, fibrosis, metabolic diseases, immune-inflammatory diseases and HCV. Targeting microRNAs with anti-miRs, chemically modified, single-stranded oligonucleotides, offers a unique approach to treating disease by modulating entire biological pathways and may become a new and major class of drugs with broad therapeutic application.
About Regulus
Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements associated with the expected ability of Regulus to undertake certain activities and accomplish certain goals (including with respect to development and other activities related to RG-101), the projected timeline of clinical development activities, and expectations regarding future therapeutic and commercial potential of Regulus' business plans, technologies and intellectual property related to microRNA therapeutics and biomarkers being discovered and developed by Regulus. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "intends," "will," "goal," "potential" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Regulus' current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. These and other risks concerning Regulus' financial position and programs are described in additional detail in Regulus filings with the Securities and Exchange Commission . All forward-looking statements contained in this press release speak only as of the date on which they were made. Regulus undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
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