Last week I discussed the history of hepatitis C. This week I focus on the evolution of hepatitis C treatment.
Treatment for chronic hepatitis C infection began in the early 1990s with interferon-alfa. The response rates were low, ranging from 10% to 20%.[i] This injectable drug worked by boosting the immune system, rather than by specifically attacking the virus. It is like giving a gun to people to fight off intruders. If you are a good shot, you win the fight; if you aren’t, you are overwhelmed with intruders.
In 1998, the oral drug ribavirin was added to interferon. The success rates increased dramatically, averaging 37% to 43%,[ii] but so did the side effects. We still don’t know precisely how ribavirin works, other than it seems to weaken HCV. A good way of looking at HCV treatment is that ribavirin cuts the leg off HCV making it easier for interferon to finish the job.
After that, the next big treatment advance occurred in 2002 with the approval of pegylated interferon-alfa, a process that makes interferon more durable and effective. Combined with ribavirin, the average patient could expect about a 52%[iii] permanent response. Pegylated interferon compared to plain interferon is like the difference between a handgun and an automatic weapon.
In 2011, two protease inhibitors were added to our arsenal—boceprevir (Victrelis) and telaprevir (Incivek). These drugs directly targeted HCV and prevent the virus from replicating. Protease inhibitors are like precision-guided weapons designed to destroy a specific virus. In case any HCV is hiding, you finish the job with peginterferon and ribavirin. The triple therapy approach was approved for genotype 1 patients with results hovering around 79%.[iv] Patients with genotypes 2 or 3 continued to use peginterferon and ribavirin without the need for a third drug. This group has good response rates at 82%.[v]
However, the success of boceprevir and telaprevir came with a terrible price as both had horrendous side effects. Patients had suffered through the older treatments, but there were terrible. We needed something new, and quickly.
At the end of 2013, simeprevir (Olysio) and sofosbuvir (Sovaldi) were approved. Treatment was now easier and more effective. However, the game changer was the approval of Harvoni (sofosbuvir and ledipasvir) in 2014.
Things didn’t stop there. Viekira Pak (ombitasvir, paritaprevir, ritonavir and dasabuvir) came out this year. Then came Daklinza (daclatasvir) for use with sofosbuvir to treat patients with genotype 3 and Technivie (ombitasvir, paritaprevir and ritonavir) for use with ribavirin to treat noncirrhotic patients with genotype 4.
Reviewing the history of hepatitis C gives me perspective. Yes, hepatitis C is still looming large. Yes, not everyone can or will be treated with 100% cure rates. Nevertheless, we have still come a long way in a short time and our weapons are improving. This allows us to work on prevention and creating a world free of hepatitis C.
[i] National Institutes of Health Consensus Development ConfeA Brief History of Hepatitis C, by Alan Franciscusrence Statement: Management of Hepatitis C Hepatology March 1997
[ii] Rebetol, Intron and Rebetron product information
[iii] Compilation of data from product information of peginterferon alfa-2a with ribavirin (Pegasys/Copegus) and peginterferon alfa-2b with ribavirin (PegIntron/Rebetron)
[iv]Incivek (telaprevir) prescribing information
[v] Compilation of data from product information of peginterferon alfa-2a with ribavirin (Pegasys/Copegus) and peginterferon alfa-2b with ribavirin (PegIntron/Rebetron)