Hepatitis C treatment has come a long way since the standard of care was nearly a year of interferon therapy; most new drugs are administered for 12 weeks, while Gilead’s Harvoni has a treatment course as short as eight weeks. Now Regulus Therapeutics has come a step closer to the ultimate aim, a four-week regimen, which could not only make therapy more convenient for patients, but also address a major issue in the sector – cost.
The company reported promising interim phase II results with its injectable microRNA treatment RG-101 given before and after a four-week course of Harvoni, Johnson & Johnson’s Olysio or Bristol-Myers Squibb’s Daklinza. But with others working on shorter-course oral regimens, including Gilead’s potentially six-week triple combination, will there be a place for Regulus’s add-on injection?
Investors seemed optimistic, pushing the group’s share price up 19% yesterday, and BMO Capital Markets analysts believe that RG-101 sales will total $568m by 2020. One factor boosting uptake would be the reduced cost of a shorter course of antivirals, but of course the price of RG-101 would also need to be taken into account.
During a conference call to discuss the data, Regulus executives would not give a figure for the combination of RG-101 and a four-week drug regimen, but the company's chief operating officer, Jay Hagan, said there was “a lot of room to position the product for best value creation”.
And while the company could partner with one of the big hep C players, with Gilead the most obvious option, it seems in no hurry to do so. Chief executive Paul Grint pointed out that maximum value would come from being able to combine RG-101 with any agent, but did add that the latest findings “should further stoke” partnering discussions.
Regulus is now focused on RG-101 as part of combination therapy, after disappointing results from a monotherapy study last year (Regulus pays dearly for its relapse, April 28, 2015).
The latest trial, with a so-called closed-face sandwich design, enrolled treatment-naïve non-cirrhotic patients with genotypes 1 and 4, who received RG-101 on day 1 and day 29.
So far, only a small proportion of the 79 patients have 12 weeks' follow-up, the period used for the primary endpoint analysis and the standard in hepatitis C trials. But in the 14 patients with 12-week data available, 100% had a viral load below the set limit. 38 patients were evaluable at eight weeks, with 97% having viral loads below the cut-off.
Regulus hopes to present more data at a scientific meeting, possibly EASL in April, and the primary endpoint analysis in the full patient group should be available late in the second quarter. Patients will be followed for 48 weeks in total.
|Interim results from Regulus’s phase II study|
|RG-101 + Harvoni||RG-101 + Olysio||RG-101 + Daklinza||Overall|
|Patients responding at follow-up week 8||12/12||14/14||11/12||37/38 (97.4%)|
|Patients responding at follow-up week 12||5/5||4/4||5/5||14/14 (100%)|
In March, Regulus plans to start an open-label phase II “open-faced sandwich” study, which will involve a single injection of RG-101 before up to 12 weeks of treatment with GlaxoSmithKline’s investigational non-nucleoside NS5B polymerase inhibitor GSK2878175. Interim results should be available by the end of the year.
Glaxo is also working on an injectable formulation of GSK2878175, which could set up future trials evaluating a single injection of each agent, with the potential to improve patient compliance.
Further into the future, RG-101 could be studied alongside drug regimens shorter than four weeks, Mr Grint said during the conference call. This seems like a sensible strategy if Regulus is to keep ahead of shrinking treatment courses for the new combos and fulfil its goal of making RG-101 a backbone therapy in hep C.
|Trial||Combination agents||Treatment period||HCV genotypes||Data due|
|Phase II closed-faced sandwich||Harvoni or Olysio or Daklinza||Four weeks||1 and 4||Q2 2016|
|Phase II open-faced sandwich||GSK2878175||Up to 12 weeks||1 and 3||Interim data YE2016|