Achillion, Regulus chase shorter HCV regimens, but can they beat Gilead?
This article was originally published in Scrip
Stock prices rose for Achillion Pharmaceuticals and fell for Regulus Therapeutics on 9 February as the companies revealed early clinical trial data that may support shorter durations of treatment for their hepatitis C virus (HCV) drugs, but HCV leader Gilead Sciences still could beat Achillion and Regulus to market with relatively fast-acting regimens.
Achillion gained as much as 18.8%, but closed up 7.8% at $11.66 per share, after the New Haven, Connecticut-based company reported sustained virologic responses at 12 weeks (SVR12) for 100% of the 12 HCV patients treated for six weeks with ACH-3102 and Gilead's Sovaldi (sofosbuvir). Separately, Regulus reported that all 14 patients treated with a single subcutaneous 4mg/kg dose of RG-101 had reduced viral loads at day 29 and at day 57 nine people had undetectable HCV.
San Diego-based Regulus reported results from the same Phase I study in October for a single administration of its 2mg/kg dose, which doubled the company's stock (scripintelligence.com, 23 October 2014). However, Regulus closed down 7.2% at $15.64 on 9 February, showing that in the current HCV market it's hard for an injectable medicine to compete against oral drugs with high cure rates. The decline also probably had something to do with news that two patients from the 2mg/kg cohort relapsed soon after day 57.
Investors may have dialed down their Achillion enthusiasm as the day wore on, and perhaps took a negative view of Regulus, because Gilead and others have drug combinations in later stages of development that may show efficacy with shorter durations of treatment in large pivotal trials before Achillion and Regulus are able to report mid-stage results for their therapies.
Foster City, California-based Gilead said earlier in February when it reported fourth quarter 2014 earnings that it will deliver results in 2015 from a Phase II clinical trial for Sovaldi plus GS-9857 and GS-5816, which could show efficacy after four to six weeks of treatment for genotype 1 and 3 HCV patients (scripintelligence.com, 4 February 2015).
Merck & Co also is testing its two drugs MK-5172 and MK-8742 in combination with Sovaldi in an ongoing Phase II trial with dosing regimens as short as four weeks with results expected in 2015 (scripintelligence.com, 8 October 2014).
Achillion data
Achillion tested six weeks of daily dosing of 50mg ACH-3102 plus 400mg of Sovaldi in a dozen treatment-naïve genotype 1 HCV patients during an ongoing Phase II clinical trial. The company said ACH-3102 plus Sovaldi was well-tolerated with no serious adverse events and no treatment discontinuations due to side effects.
Achillion previously reported that 100% of patients treated for six weeks achieved a sustained viral response at four weeks (SVR4), but SVR 12 is the trial's primary endpoint (scripintelligence.com, 23 December 2014). Before that, Achillion said in November that all 12 patients who received ACH-3102 and Sovaldi for eight weeks achieved SVR4, SVR8 and SVR 12.
"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 II 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," lead investigator Edward Gane said in a statement from Achillion.
Dr Gane is deputy director and hepatologist in the New Zealand Liver Transplant Unit at Auckland City Hospital in New Zealand.
"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," Achillion president and CEO Milind Deshpande said. "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."
The company revealed Phase I ACH-3422 results in December alongside its last Phase II ACH-3102/Sovaldi update and said at that time that it would advance ACH-3102 and ACH-3422 in Phase II combination studies to test shorter durations of oral HCV therapies.
"We are currently preparing to initiate our SPARTA Phase II 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," Achillion chief medical officer David Apelian said on 9 February.
Regulus results
Regulus developed RG-101 with RNA-based technology from the company, Isis Pharmaceuticals and Alnylam Pharmaceuticals. The drug targets microRNA-122 (miR-122), a microRNA that HCV uses to replicate, to keep miR-122 from binding to HCV.
The mean viral load reduction for the 14 patients in the ongoing Phase I study who received a single subcutaneous 4mg/kg dose of RG-101 was 4.8 log10 at day 29 with a range of -5.8 to -3. The nine patients who had HCV RNA levels below the limit of quantification (BLOQ) at day 57 will be monitored for six months to determine whether any individuals are cured with a single 4mg/kg dose.
Regulus also plans to add a year of follow-up to the 2mg/kg arm of the study to determine potential long-term cure rates for that dose. BLOQ was achieved for patients in both dosing cohorts regardless of HCV genotype and liver fibrosis status, and regardless of whether they'd failed previous treatment for hepatitis C.
"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," Regulus president and CEO Kleanthis Xanthopoulos said in a statement from the company.
Regulus chief medical officer Paul Grint noted that the company will begin Phase II monotherapy and combination therapy studies with RG-101 during the second quarter of 2015.