CHI Report – Innovation in Hepatitis C Treatment – Page – 6
The Rise of Hepatitis C Treatments
In the early 1980s, reports of a progressive, infectious liver disease that could not be classified as hepatitis A or B led researchers to create a new non-A/non-B (NANB) hepatitis disease category. Initially, NANB hepatitis was thought to be harmless, but its silent progression to cirrhosis or liver cancer soon came to light. In 1989, a researcher at Chiron identified the causative agent of NANB hepatitis and called it Hepatitis C virus. xviii Since then, treatment of the disease has been the subject of intense research by academic scientists and pharmaceutical companies alike. The search for medicines has been focused on finding compounds that can produce a sustained viral response (SVR), an effective measure of a cure, meaning that no detectable virus is present in the patient’s blood after completion of treatment. Numerous studies have demonstrated that patients who achieve a SVR face very low probabilities of disease progression and death due to hep C.
Exhibit 4 provides an overview of the remarkable progression of technological innovations in the treatment of hep C. In the early 1960s, all hepatitis disease was treated with strict bed rest and a nutritious diet. No chronically infected patients were cured with this approach.
In 1986, inspired by the success of interferon in the treatment of hep B, the National Institutes of Health encouraged a study of interferon’s efficacy in what was then known as NANB hepatitis (hep C). The results were disappointing: although many patients responded to treatment initially, most of them relapsed. Still, six percent achieved an SVR. Soon, however, ribavirin was added to the treatment regimen and interferon was chemically modified to persist longer in the patient’s body through a process called pegylation. The new pegylated-interferon-and-ribavirin regimens were an important breakthrough in the treatment of hep C. For the first time, the SVR for genotype 1 patients approached 50 percent, and the SVRs for genotypes 2 and 3 were even more promising (78 percent and 62 percent, respectively). 9, iv, xviii
The trouble was that these regimens offered no hope for more than half of genotype 1 patients and, even when they worked, the treatment came with distressing side effects, including depression, nausea, severe reductions of certain blood cells, and flu-like symptoms. iii Beyond suffering and sickness from these side effects, patients required additional health-care services (including, sometimes, hospitalization) for their management. From a patient’s standpoint, these interferon-based treatments posed a large and difficult treatment burden: weekly interferon injections for 48 weeks and twice-daily ribavirin pills. iv The side effects, the daunting treatment burden, as well as the suboptimal efficacy of interferon-based therapy caused many patients to discontinue treatment before completion, thus all but eliminating their chances of achieving SVR. In a study among US veterans, as many as 54 percent of patients initiating interferon-based treatment failed to complete their course of treatment. xxi
The search for better medicines continued and, in 2011, two new drugs were approved by the US FDA. The new drugs, telaprevir and boceprevir, are protease inhibitors (PIs); they work by inactivating a critical piece of the Hepatitis C virus machinery called the protease. The improved regimen still required 24 to 48 weeks of weekly injections combined with eight oral tablets daily. Although PIs substantially improved the rate of SVR attainment for genotype 1 patients, they had to be taken together with interferon and ribavirin, which meant that they worsened the side effects and treatment burden of those regimens. iv
The ultimate goal of hep C drug research has been the discovery of a treatment that can be taken orally, has minimal side effects, and cures all patients of the virus. In 2013, the US FDA approved the first of an expected series of new drugs that align with these desired characteristics. Sofosbuvir, the first of these new compounds to reach the market, gives patients a 12-week, all-oral regimen, achieving SVRs of 97 percent and 93 percent in genotype 2 and genotype 3 patients, respectively, when taken together with ribavirin (without interferon). iv Soon, additional drug launches by AbbVie, Bristol-Myers Squibb, Gilead Sciences, and Merck & Co. will offer various interferon-free regimens, which are expected to have SVRs above 95 percent for all genotypes 10 , including genotype 1, the most prevalent form of the disease in the US. In addition, they are expected to be administered orally only (one to five pills per day for 12-24 weeks) with limited side effects.
8 Importantly, the increases in investments in HIV and AIDS coincided with the discovery of improved medicines that could change the course of the disease for thousands of people. The Ryan White CARE Act, which funds HIV and AIDS treatment for patients with no other resources, was passed by Congress in 1990, the same year that the U.S. FDA approved AZT, the first anti-HIV medication. The act was reauthorized in 1996, just one year after saquinavir was approved by the FDA, marking a new era of improved treatments against HIV and AIDS.
9 The SVRs cited in this report come from highly controlled clinical trials. The real-world SVRs of these regimens have been found to be substantially lower because of differences in the clinical and behavioral characteristics of hep C patients who are not treated and followed in a clinical trial.