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HCV therapies: Changing the paradigm
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For Eric Lawitz, MD, research is its own reward.
The medical director of the Texas Liver Institute and clinical professor of medicine at University of Texas Health, San Antonio, spoke with Healio about continually pushing the envelope for hepatitis C innovation—and what comes beyond the blockbusting recent advances in HCV treatment.
Discuss your background and how you became interested in HCV and hepatology.
Hepatology has always been intriguing as historically many of our diseases have suboptimal therapies. Among the diseases yet to be conquered when I started my career was hepatitis C. HCV became an obvious target as it is an RNA virus, and it seemed inconceivable that drug discovery researchers would not have eventually developed antiviral therapy. It was clear to me that this should be a curable virus, but for many years we did not have the necessary tools to develop optimal therapies. When researchers Ralf F. W. Bartenschlager, Charles M. Rice and Michael J. Sofia finally perfected the hepatitis C replicon system after years of trial and error, the speed of innovation accelerated. Finally, as antivirals emerged, investigation of these novel and exciting agents became my focus and my passion! Certainly, my goal was to help foster these compounds and aid in their development.
What is unique about the Texas Liver Institute?
The Texas Liver Institute (TLI) is not significantly different from other tertiary-level liver centers, but it is based on three key pillars: excellence in clinical care; innovative and collaborative clinical trials; and education of the community, staff, peers and other health care professionals, including trainees.
What are some career highlights related to HCV that you’re most proud of?
I am very proud of my involvement in the revolutionary transition of hepatitis C therapy. We have eliminated interferon and ribavirin from the treatment regimen and replaced them with direct-acting antivirals (DAAs). Cure rates above 95% are routine, and adverse event profiles are basically similar to placebo. Having been at the tip of the sword and doing my part to aid the development of these highly effective antivirals, we as a medical community witnessed the transition from an immune-based therapy with marginal effectiveness, to DAA therapy with virtually universal success. This revolutionary sequence of events is something I hope to share with my grandchildren as I ponder these events sitting in a rocking chair.
What HCV research/clinical trials are you currently involved in, and what data/results can you share with our readers?
Fortunately, we have reached a point where hepatitis C research is just about wrapped up, and researchers have no additional motivation to look for more potent antivirals or new immune approaches that might shorten therapy to ultra-short durations. Given the lack of enthusiasm in this regard, I probably presented my last hepatitis C data during Digestive Disease Week in Washington, D.C., in 2018, where I presented two abstracts, the first focusing on patients with renal disease and the second looking at triple combination salvage therapy. Despite the loss of further innovation in hepatitis C, I am still very busy and focused at TLI where we have robust clinical development across the spectrum of hepatology diseases. Now that HCV research is complete, I have the time to explore more of my passions that include nonalcoholic steatohepatitis, fibrosis, primary biliary cholangitis and hepatitis B. We at TLI will continue to push the field as best as we can and continue to collaborate on innovation in our field.
Now that HCV is curable, are there any remaining challenges in the treatment of HCV that keep you up at night, and how are you and your team helping to approach these challenges?
Although there are currently no new agents in development for HCV, more can still be done. I would like to investigate ultra-short durations, including single-dose, directly observed therapy. Currently, HCV treatment is generally 8 to 12 weeks in duration; however, it is conceivable to achieve an even shorter treatment duration. Durations from single-dose to 4 weeks is possible with much more potent antivirals likely in combination with an immune-based therapy. Despite all the successes with HCV treatment, reducing the treatment duration would be quickly accepted in the marketplace as long as SVR12 rates are maintained and there is no interval increase in the adverse events. Such a therapy could replace our current standards of care and dominate the HCV landscape. This concept gives us one last opportunity for a paradigm shift in HCV therapy. A single-dose therapy, directly observed in the office would enhance patient compliance and make treatment administration even simpler. Additionally, it would aid in reaching the global eradication goal. I still have hopes that drug developers would look at this as the next and final step in HCV therapy innovation.
What concluding remarks would you like to share with readers about HCV?
I think it is important everyone realize how revolutionary the change has been in HCV therapy that we have just lived through. The transition from a very poorly tolerated therapy with low success rates to universal success without significant adverse events is nothing short of amazing. It has been a blessing to be so intimately involved with this rapidly changing field, and it has truly been a medical transformation in how we treat hepatitis C. The history books will acknowledge the level of innovation, speed of development and rapid paradigm shifts as we read about the revolutionary changes in how hepatitis C is treated!