Atea Aims For Underserved HCV Niche With Combo Regimen

Having ended work with its polymerase inhibitor bemnifosbuvir in treating COVID-19 infections, Atea Pharmaceuticals is returning to its original focus on hepatitis C and reported Phase II data for a combination regimen on 4 December that it hopes will lead to a Phase III program in 2025. The Boston-based firm will attempt to find a treatment niche with a product it says can offer convenience and compliance advantages compared to the standard of care.

Atea’s bemnifosbuvir combined with ruzasvir, an NS5A inhibitor licensed from Merck & Co. in 2022, achieved a 98% (208/213) sustained virologic response rate at 12 weeks (SVR12) after completion of an eight-week treatment period in treatment-adherent patients who had not previously received direct-acting antiviral therapy for HCV. The company noted that a broader cohort from the 275-patient study of “evaluable patients,” which included 17% who weren’t fully compliant with therapy, achieved a 95% (242/256) SVR12 rate as well.

Atea also highlighted the combination’s pan-genotypic efficacy, with a 99% (178/179) SVR12 rate across genotypes 1-4 in non-cirrhotic HCV-infected patients. The one treatment failure came in the study’s genotype 1 cohort (119/120). Among cirrhotic patients who adhered to treatment over the eight-week period, the combo yielded an SVR12 rate of 88% (30/34).

The combo was also generally safe and well-tolerated, Atea pointed out, with no drug-related serious adverse events reported or treatment discontinuations in the open-label trial.

While the introduction of direct-acting antivirals with near 100% efficacy has served the market well, Atea hopes to build a case that the US HCV-infected patient population is younger – primarily people between 20-49 – and healthier, with less than 10% being cirrhotic. Therefore, the company reasoned, US patients might be more responsive to and compliant with a short-term regimen with good safety and tolerability with little incidence of drug-drug interactions (DDI).

Challenge Of Finding A Treatment Niche

Analysts, however, have been skeptical about Atea’s ability to find a significant commercial opportunity in a declining HCV market against established standard-of-care regimens – AbbVie’s Mavyret (glecaprevir/pibrentasvir) and Gilead’s Epclusa (sofosbuvir/velpatasvir).

J.P. Morgan analyst Eric Joseph said in a 7 November analysis that while the Atea combo appeared headed for Phase III, “we remain skeptical of the bemi’ + ruza’ value proposition, specifically that a meaningful level of unmet need in HCV (largely in the form of poor compliance), can be served by an eight-week, favorable DDI profile [compared] to Mavyret.”

Datamonitor Healthcare scientific analyst Ken Hoang told Scrip that he also doesn’t see a major opportunity for differentiation from the standard of care for Atea’s regimen.

“With all the caveats of cross-trial comparisons, these SVR results compare well to data from pan-genotypic regimens Epclusa (SVR12 rate of 98% in ASTRAL-3) and Mavyret (approximate SVR12 rate of 99% across different studies),” he noted. “Despite the positive data, it is challenging for Atea to differentiate its combination regimen, given that there are no significant remaining unmet needs in HCV and the impracticality of demonstrating improvement in efficacy/safety via head-to-head trials due to a near 100% cure rate.”

“However, Atea could attempt to address the unmet need for a convenient therapy with low risk of drug-drug interactions as noted in its slides, which could improve patient adherence to achieve cure,” Hoang added.

Given Atea’s clinical trial failure with bemnifosbuvir in COVID-19, the analyst called the Phase II readout in HCV “a much-needed win” for the company and Hoang increased the combo’s likelihood of approval by 2%, but he reiterated his concerns about the viability of a new therapy “in the face of the ever-shrinking HCV market.”

William Blair’s Andy Hsieh was more optimistic, however, in a 7 November analysis. He noted that HCV studies using SVR12 as a primary endpoint “have historically translated well to late-stage pivotal studies.” Hsieh took a bullish stance on the prospects for the Atea combo, as a “drug-drug interaction-free and short-course HCV regimen.”

He noted that the eight-week treatment duration – although Atea said it will test and recommend 12 weeks of treatment for patients with cirrhosis – matches the standard length of treatment with Mavyret, while the combo’s low incidence of DDIs makes it a candidate that “essentially merges the best clinical characteristics of Mavyret and Gilead’s Epclusa.”

In a 4 December note reacting to the data, Hsieh said he was “impressed by the 100% cure rate among non-cirrhotic patients living with genotype 3 infection, which is notoriously the most difficult-to-treat genotype.” The Phase II findings “materially de-risk the planned Phase III global program that is slated to initiate early next year and will feature 800 patients across two studies,” he added.

Atea is seeking an end-of-Phase II meeting with the US Food and Drug Administration in early 2025, with a goal of beginning its Phase III program later in the year. The company plans to use a fixed-dose combination of the two drug candidates in Phase III, which would reduce patients’ daily pill burden from four to two tablets, intended to further benefit therapeutic compliance, and will test its combo against an unnamed active comparator.

Coming out of its third quarter earnings report on 7 November, Atea had $482.8m in cash, which it said would be sufficient to fund operations into 2027. The company exited stealth and raised $215m in venture capital funding in 2020 based on a plan to develop bemnifosbuvir for COVID-19. Atea launched its initial public offering five months later, grossing $300m in its October 2020 IPO.