Hopes for single-dose Hepatitis C drug fade

Shares of Regulus fall but company, analysts still see promise 

LOS ANGELES (MarketWatch) — Shares of Regulus Therapeutics took it on the chin Monday after the biopharmaceutical company reported spotty results in tests for a drug designed to cure Hepatitis C with a single dose.

Regulus RGLS, +1.55%  shares dropped 10% to $15.15, as it appeared its drug, now designated as RG-101, will have to be accompanied by other treatments in many patients in order to cure Hepatitis C.

The company said RG-101 appeared to wipe out traces of the disease in four of 14 patients with a 2-milligram dose. This test was critical because it showed the drug’s ability to keep Hepatitis C at bay for 85 days. Patients who show no signs of Hepatitis C after 84 days are considered cured. 

Read more...

Regulus' experimental microRNA therapy RG-101 Update

All HCV Patients Treated with a Single SC Administration of 4 mg/kg of RG-101 Responded with Mean Viral Load Reduction of 4.8 log10 at Day 29 and 9/14 Patients are Below the Limit of Quantification at Day 57

 -Extended Follow-Up Shows 4/14 Patients Treated with a Single SC Dose of 2 mg/kg of RG-101 are Target Not Detected at Day 85 -

- Study Enrolled HCV Patients with Multiple Genotypes, Liver Fibrosis Status and Prior Treatment History -

- Conference Call Today at 8:00 a.m. EST to Discuss Results -

LA JOLLA, Calif., Feb. 9, 2015 /PRNewswire/ -- Regulus Therapeutics Inc. (NASDAQ:RGLS), a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs, today announced top-line results from the 4 mg/kg cohort and additional results from the 2 mg/kg cohort in a completed clinical study evaluating RG-101, a wholly-owned, GalNac-conjugated anti-miR targeting microRNA-122 ("miR-122"), for the treatment of hepatitis C virus infection ("HCV").  Treatment with a single subcutaneous dose of 4 mg/kg of RG-101 as monotherapy resulted in significant and sustained viral load reductions in all patients, including difficult to treat genotypes, various liver fibrosis status and those who have experienced viral relapse after a prior IFN-containing regimen.  To date, RG-101 continues to have a favorable safety profile with no serious adverse events or discontinuations reported in the treated HCV patients.

Top-line results from the 4 mg/kg dose cohort:
In the 4 mg/kg dose cohort, 16 HCV patients were enrolled: 14 patients, 12 naive and 2 patients who experienced viral relapse after a prior IFN-containing regimen, received a single subcutaneous dose of 4 mg/kg of RG-101 as monotherapy, and 2 patients received placebo.

• In the 14 treated HCV patients, there was a mean viral load reduction of 4.8 log₁₀ at day 29 (range -5.8 to -3.0); and
• 9 out of 14 patients had HCV RNA levels below the limit of quantification ( < 15 IU/ml) ("BLOQ")  at day 57 and these patients will be followed up to six months to investigate the potential for viral cures following the single administration of 4 mg/kg of RG-101.

Extended follow-up results from the 2 mg/kg dose cohort:
In October 2014, Regulus reported interim efficacy and safety results and its first human proof of concept results from the 2 mg/kg cohort of the completed study evaluating RG-101 for the treatment of HCV. 

• At day 85, 4 out of 14 treated patients with varied genotypes, liver fibrosis status and treatment history were Target Not Detected ("TND"); 2 of the treated patients that were BLOQ at day 57 relapsed shortly thereafter; and
• Due to the longevity of the viral responses demonstrated, the protocol is being amended to add an additional year of follow up to investigate the potential for viral cures with one single administration of RG-101.

Summary of 2 mg/kg and 4 mg/kg dose cohort results:
Treatment with a single subcutaneous dose of either 2 mg/kg or 4 mg/kg of RG-101 as monotherapy has resulted in significant and sustained viral load reductions in all patients including difficult to treat genotypes, various liver fibrosis status and those who have experienced viral relapse after a prior IFN-containing regimen.  At day 57, 15 out of 28 patients treated with one single administration of either 2 mg/kg or 4 mg/kg of RG-101 had HCV RNA levels BLOQ and 12 out of these 15 treated patients were TND. 

"The profile of RG-101 has been significantly enhanced with these top-line data, making it an ideal pan-genotypic asset to investigate further in combination with all classes of oral agents to shorten the duration of treatment, increase patient compliance and maintain viral response, and also as monotherapy in certain underserved HCV populations," said Kleanthis G. Xanthopoulos, Ph.D., President and CEO of Regulus.  "With the promising data reported today, our confidence in our ability to treat diseases with microRNA therapeutics is higher than ever and we look forward to continuing to execute our 'Clinical Map Initiative' goals for RG-101 and our microRNA therapeutics pipeline."

"We continue to be pleased with the clinical results demonstrated with RG-101 and have a much more robust data set to inform our dual-track clinical development plans for Phase II," said Paul Grint, M.D., Chief Medical Officer of Regulus. "We have filed our pre-IND briefing book with the U.S. Food and Drug Administration and are working to file a Clinical Trial Application to conduct monotherapy and combination studies in multiple countries. In the second quarter of 2015, we look forward to initiating these studies and reporting full results from the completed study."

"These results demonstrate a significant breakthrough in the treatment of HCV," said Hendrik W. Reesink, M.D., Ph.D., Associate Professor in the Department of Gastroenterology and Hepatology at the Academic Medical Center in The Netherlands.  "These landmark studies were conducted with a high level of novelty and practical clinical importance.  All twenty-eight patients treated with one administration of RG-101 responded and more than 50% had HCV RNA levels below the lower limit of quantification at day 57.  I look forward to seeing RG-101 rapidly advance in Phase II to test its utility in combination with oral agents and possibly as monotherapy."

Conference Call & Webcast Information
Regulus will host a conference call and webcast at 8:00 a.m. Eastern Standard Time today to discuss the RG-101 results.  A slide presentation will also be available on Regulus' website, www.regulusrx.com to accompany the live webcast.  To access the call, please dial (877) 257-8599 (domestic) or (970) 315-0459 (international) and refer to conference ID 80841144.  To access the telephone replay of the call, dial (855) 859-2056 (domestic) or (404) 537-3406 (international), passcode ID 80841144.  The webcast and telephone replay will be archived on the company's website for ninety days following the call. 

About RG-101 for HCV
RG-101 is Regulus' wholly-owned, GalNAc-conjugated anti-miR targeting miR-122 for the treatment of HCV. Regulus has evaluated RG-101 in a completed clinical study conducted in the Netherlands. 58 healthy volunteers and 32 HCV patients with multiple genotypes, liver fibrosis status and treatment history were enrolled in the four part study: (i) a single ascending-dose study in which healthy volunteer subjects received a single subcutaneous dose of RG-101, 0.5 mg/kg, 1 mg/kg, 2 mg/kg, 4 mg/kg and 8 mg/kg or placebo; (ii) a multiple-ascending dose study in which healthy volunteer subjects received a monthly single subcutaneous dose for four months of RG-101 or placebo; (iii) a single-dose drug-drug interaction study in which healthy volunteer subjects received a single subcutaneous dose of RG-101 in combination with simeprevir (OLYSIO™), an approved direct acting antiviral; and (iv) a single-dose study in which HCV patients received either a single subcutaneous dose of RG-101 or placebo at two doses, 2 mg/kg of RG-101 (the first dose cohort) or 4 mg/kg of RG-101 (the second dose cohort), to assess the safety and viral load reduction.  Dosing in part IV is complete and extended follow up is ongoing.  The primary objective is to evaluate safety and tolerability and the secondary objectives are to evaluate pharmacokinetics, viral load reduction and any impact an oral direct acting antiviral, such as simeprevir (OLYSIO™), may have on the pharmacokinetics of RG-101. 

Today, Regulus reported additional results from the above study and plans to report full study results in the second quarter of 2015.

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 500 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.

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 350,000 people die from HCV annually.  The CDC estimates that there are currently approximately 3.2 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.  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.

'Clinical Map Initiative' Goals for RG-101
Regulus' 'Clinical Map Initiative' outlines certain corporate goals to advance its microRNA therapeutics pipeline over the next several years.  To rapidly advance RG-101, Regulus is pursuing a Phase II dual-track clinical development strategy (i) to investigate RG-101 in combination with oral agents to potentially shorten treatment durations, optimize clinical outcomes and potentially improve responses in certain underserved HCV patient populations; and (ii) to investigate RG-101 further as a single agent to determine whether HCV viral cures are achievable with monotherapy treatment (single or multiple doses of RG-101).  In the near term, Regulus expects to file both a Clinical Trial Application and an Investigational New Drug application for RG-101 with the goal to initiate the above described studies in Europe and the United States in the second quarter of 2015.

About Regulus
Regulus Therapeutics Inc. (NASDAQ:RGLS) is a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs.  Regulus has leveraged its oligonucleotide drug discovery and development expertise to develop a well-balanced microRNA therapeutics pipeline complemented by a maturing microMarkers^SM biomarkers platform and a rich intellectual property estate to retain its domain dominant leadership in the microRNA field.  Under its 'Clinical Map Initiative', Regulus is developing RG-101, a GalNAc-conjugated anti-miR targeting microRNA-122 for the treatment of chronic hepatitis C virus infection, and RG-012, an anti-miR targeting microRNA-21 for the treatment of Alport syndrome, a life-threatening kidney disease driven by genetic mutations with no approved therapy.  Regulus is also advancing several programs toward clinical development in orphan disease indications, oncology and fibrosis.  Regulus' commitment to innovation has resulted in multiple peer-reviewed publications in notable scientific journals and has resulted in the formation of strategic alliances with AstraZeneca and Sanofi and a research collaboration with Biogen Idec focused on microRNA biomarkers.  Regulus maintains its corporate headquarters in La Jolla, CA.

 For more information, please visit http://www.regulusrx.com.

Achillion Achieves 100% SVR12 in Phase 2 Trial Evaluating 6-Week Combination Treatment With ACH-3102

- Achillion achieves 100% SVR12 in six-week regimen with combination of ACH-3102 and sofosbuvir for treatment-naïve genotype 1 HCV -

- Achillion to initiate 4-week treatment regimens based on the strength of ACH-3102 antiviral data -

NEW HAVEN, Conn., Feb. 9, 2015 (GLOBE NEWSWIRE) --Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced updated interim results from the ongoing interferon-free, ribavirin-free, Phase 2 study to evaluate the efficacy, safety, and tolerability of six weeks of 50 mg of ACH-3102 and 400 mg of sofosbuvir, a marketed nucleotide polymerase inhibitor, in treatment-naïve genotype 1 HCV-infected patients. The primary objective of the study is determination of sustained viral response 12 weeks (SVR12) after completion of therapy. One hundred percent of patients (12/12) in the six-week treatment duration arm achieved SVR12, which included patients with high baseline viral load.

"The ability to further shorten treatment duration to only six weeks and maintain excellent SVR12 rates remains the goal for clinicians and patients, and I am pleased that these Phase 2 results support that goal. The profile of ACH-3102, represents an important and exciting treatment option to shorten treatment duration for patients infected with HCV," commented Professor Edward Gane, M.D., Deputy Director and Hepatologist, New Zealand Liver Transplant Unit, Auckland City Hospital in New Zealand, and Lead Investigator in the Phase 2 study of ACH-3102 and sofosbuvir and the ACH-3422 nucleotide inhibitor program.

Dr. Milind Deshpande, President and Chief Executive Officer of Achillion, commented, "Our goal is to deliver short duration, widely accessible treatments to all HCV patients. We believe that these results with ACH-3102 represent the shortest duration and highest response achieved to date with any two-drug, direct-acting antiviral regimen for HCV. Given the exceptional profile of ACH-3102, we will now be evaluating four- and six-week treatment durations that leverage all of our HCV assets including ACH-3102, ACH-3422, and sovaprevir."

Overview of Phase 2 Proxy Study Design and Top-line Results
This ongoing study is a Phase 2 open-label, randomized, partial-crossover study to evaluate the efficacy, safety, and tolerability of eight- and six weeks of 50 mg of ACH-3102 and 400 mg of sofosbuvir, a marketed nucleotide polymerase inhibitor, once daily, in treatment-naïve genotype 1 HCV-infected patients. Initially, eighteen patients were enrolled, including six observational patients, into an eight-week treatment cohort.

Following the achievement of 100 percent SVR12 (12/12) in the eight-week cohort, the six-week treatment cohort was initiated. In all, eighteen patients were enrolled, including twelve active and six observational patients. Mean baseline HCV RNA viral load was 10 million (7 log₁₀) IU/ml, range 2 million (6.23 log₁₀) - 97 million (7.99 log₁₀) IU/ml, including seven patients with baseline HCV RNA viral load exceeding 6 million (6.78 log₁₀) IU/ml. Of the 12 active patients enrolled, seven patients were genotype 1a and five were genotype 1b.

Twelve weeks after the completion of therapy, 100 percent (12/12) achieved SVR12, independent of baseline viral load, gender, and IL28B status, in the six-week treatment arm. Additionally, one hundred percent of patients (12/12) in the eight-week treatment duration arm have achieved SVR24. The combination of ACH-3102 and sofosbuvir was well-tolerated with no serious adverse events, no discontinuations due to adverse events, and no clinically significant laboratory or ECG abnormalities.
"The achievement of 100% SVR12 after six weeks of treatment with a dual NS5A-nucleotide regimen, even in patients with high baseline viral load who would otherwise require extended duration treatments, supports our belief that ACH-3102 can unleash the potential of this combination to drive down treatment duration," commented Dr. David Apelian, Executive Vice President of Clinical Development and Chief Medical Officer at Achillion. "We are currently preparing to initiate our SPARTA Phase 2 program which evaluates short treatment durations with our proprietary once-daily regimens of ACH-3102 and ACH-3422, with or without sovaprevir, for treatment naïve genotype 1 HCV patients. In parallel, we plan on exploring sofosbuvir-sparing regimens that will leverage shorter durations of sofosbuvir in combination with ACH-3102 and sovaprevir as part of our global development program."

Read complete press release here...

Worldwide treatment of hepatitis C could be within sight at the right cost

Lowering the cost of hepatitis C drugs is possible and it is key to achieving global access to treatment, according to new research.

There are an estimated 185 million people infected with the hepatitis C virus worldwide and 160,000 in Britain. Currently there is no vaccine and, if left untreated, infection can lead to cirrhosis and liver cancer, causing up to 500,000 related deaths globally per year. Hepatitis C is particularly problematic in low to middle income countries; for example 12 million people are infected in Egypt.

A new and effective generation of direct-acting antiviral drugs (DAAs) has been developed to treat hepatitis C (see sidebar). However, at present these drugs are highly expensive. A 12-week course of the new drug sofosbuvir in the US is priced at as much as $84,000 per person and £55,440 in the UK. The NHS has recently delayed introduction of sofosbuvir due to its high price.

Reference: van de Ven, N. et al. ‘Minimum target prices for production of direct acting antivirals and associated diagnostics to combat Hepatitis C Virus.’ Hepatology (2014) DOI: 10.1002/hep.27641

Read more...

Only the Sickest Hepatitis C Patients Get High Cost Drugs in Medi-Cal

Drugs may be behind her, but Lovelace now lives with Hepatitis C, a result of her drug use. The disease is damaging her liver.

“I can sleep 20 hours a day, literally, with no interruptions, just sleep," she says.

The treatment Lovelace needs could cost the state as much as $85,000 for a full course.  Only people with advanced liver disease or other severe related conditions are eligible for the treatment under Medi-Cal.

Read more...

A New Liver and the Right Care Make a Rutgers Patient Feel Young Again

The liver transplant center at Rutgers New Jersey Medical School is one of just two such units in the state

 
Mati Muñoz is 65 years old – filled with the enthusiastic energy that comes with a second chance at life. A decade ago, says Muñoz, who lives in Woodbridge Township, N.J., her liver was being destroyed by hepatitis C, a viral disease she believes she contracted as a girl in her native Cuba from a poorly sterilized needle used in a medical procedure.

“My coworkers said I looked like a ghost,” Muñoz recalls. Her symptoms included insomnia, depression, bloating, nausea – and an especially nasty decline in mental function caused by blood toxins that were degrading her brain.

Muñoz went on a registry to receive a liver transplant and over the next two years her symptoms intensified as she waited for a suitable donor.

Read more...

Canada: Hepatitis C common in our community

The Cape Breton District Health Authority has seen an increase in the number of hepatitis C cases over the last number of years.

In 2013, the district had 24 per cent of all hepatitis C cases in the province. This translates into approximately five new cases of hepatitis C being diagnosed every month in the district.

The World Health Organization has deemed hepatitis C a “viral time bomb” given that 2-3 per cent of the world’s population (123-170 million people) is infected with this virus.

Read more...