Provided by Drug Discovery & Development
Wed, 05/14/2014 - 1:47pm
Christina Jakubowski, News Editor
AbbVie is tossing its metaphorical hat into the quickly growing and highly competitive hepatitis C treatment ring with an experimental, all-oral, interferon-free regimen – one that is boasting sustained viral response rates 12 weeks post treatment (SVR12 rates) that range from 90 to 100%.
While the research-based biopharmaceutical company, which split from parent company Abbott Laboratories in early 2013, may be a relative newcomer, the folks behind the pipeline are no strangers to virology.
“AbbVie has a longstanding history of development work in virology dating back to the early 90s. We introduced one of the first protease inhibitors for HIV in 1996 and followed that with Kaletra in 2000,” says Barry Bernstein, MD, AbbVie’s vice president of infectious disease development. “Early in the last decade, we then turned our attention to start work on hepatitis C, using much of what we’d learned from the HIV development activities. Our work was expanded through a collaboration with Enanta, which was formed in 2006. Since then, we’ve advanced a number of different compounds into the clinic.”
The culmination of that hard work came in mid-April of this year, when AbbVie submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for the use of its experimental regimen in patients with chronic genotype 1 (GT1) hepatitis C virus (HCV). That was quickly followed by the submission of multiple marketing authorization applications (MAAs) for the same regimen, and the same use, to the European Union (EU) in early May.
Both submissions are backed by a breakthrough Phase 3 clinical trial program. The pivotal TURQUOSE-II trial showed viral response rates of 91.8% and 95.9% after 12 and 24 weeks of treatment, respectively. These rates are in patients considered to be a “difficult-to-treat” population: those who have GT1 HCV and compensated liver cirrhosis.
“The Phase 3 program involved six different clinical trials which were targeted to different populations. They ranged from patients who had not received prior treatment, they had no evidence of cirrhosis, to patients who had advanced disease with compensated cirrhosis and who had failed prior therapy with interferon- and ribavirin-based regimens. So, it was a broad spectrum of patients, which we think reflects the population currently infected with the hepatitis C virus,” says Bernstein. “The studies enrolled rapidly, I think reflecting, in part, a great deal of excitement about the potential for these interferon-free therapies to really transform the face of HCV treatment.”
Bernstein was “pleased” with these overall response rates. “We felt that they reflected the new regimen’s potential to [help] a vast majority of patients with HCV infection,” he says.
He added: “We had previously performed a Phase 2b trial, the AVIATOR study, and in that study we achieved SVR rates as high as 99% in some populations. This Phase 3 program expanded on that, to additional populations including cirrhosis, and overall we saw similar response rates confirming the Phase 2b data. So, response rates in the various arms of the study ranged from 90 to 100%.”
While awaiting approval in both the United States and EU, AbbVie will continue to make strides in other areas of its hepatitis C program. According to Bernstein, the company currently has a Phase 3 program in Japan, and is looking to initiate work in China soon. Perhaps most promising is AbbVie’s recently presented data out of Egypt, where genotype 4 HCV is endemic.
“[In Egypt], we enrolled both treatment-naïve and treatment-experienced genotype-4-infected patients,” Bernstein says. “There, we saw SVR rates as high as 100%, so we are very encouraged by those results.”
Abbvie’s regimen, which consists of the fixed-dose combination of ABT-450 and ritonavir, co-formulated with ABT-267 (ombitasvir), dosed once daily, and ABT-333 (dasabuvir) – with or without ribavirin – dosed twice daily, faces tough competition if approved. Gilead’s Sovaldi (which carries a controversial price tag) was approved by the FDA in December 2013 and by the European Medicines Agency (EMA) in January. In the pipeline at Bristol-Myer Squibb is a dual regimen of daclatasvir and asunaprevir, which has received Breakthrough Therapy Designation from the FDA. An NDA for the BMS treatment is also pending.
So what sets AbbVie’s treatment apart?
“We feel the most important characteristic of a regimen is its ability to cure patients. This is a devastating disease and it has a tremendous impact on patients’ quality of life as well as morbidity and mortality. So, the ability to cure is by far the most important characteristic of the regimen,” Bernstein says. “We’ve focused our development program on maximizing the SVR (or cure) rates that we can achieve with our therapy. So, we have targeted different populations with slightly different regimens to meet that objective and we feel that with the SVR rates that we are seeing in Phase 3, our regimen will provide an important option for patients with hepatitis C.”
With hopeful expectations for U.S. approval of the new regimen by the end of 2014, Bernstein is also looking to the pipeline for future hepatitis C drug development. There, he sees potential next-generation treatments, which have already progressed to Phase 2 at AbbVie, for patients with all genotypes.
“There are other genotypes, genotype 4 and genotype 3 in particular, where there is still significant unmet medical need. We are working on next-generation compounds that will address those needs,” he says. “These compounds include a protease inhibitor and an NS5A inhibitor with activity against all genotypes, as well as activity against many of the resistance-variants that emerge with first-generation therapy use. So, we feel that these will have utility there.”
Yet despite all the excitement surrounding the pharma companies that are developing hepatitis C compounds and regimens, Bernstein adds that it’s important to remember the people who are truly benefitting from these drug discoveries.
“It’s a particularly exciting time for patients in need of improved therapies,” he says. “We’re very, very happy to be contributing to that effort – to improve treatments for hepatitis C.”