HCV Advocate News & Pipeline Blog: Top News – 2015

There was much news in 2015 about hepatitis C (HCV), but most of the news was driven by the high cost of HCV medications—specifically the market leader –Gilead’s Harvoni to treat HCV genotype 1. In 2015, there was another interferon-free HCV Drug approved—AbbVie’s Viekira-Pak. Viekira-Pak carried a high price tag, but it was a little less than Harvoni. The other news tied to the high cost of the medications included the access (or lack of) to the drugs, exclusivity deals, and generic versions of the new HCV drugs. The other news that I will discuss includes the approval of Daklinza and Technivie, safety warnings, a new cell culture, the advocacy community and my wish list for 2016.

Gilead, AbbVie & The Price Tag

The Food and Drug Administration (FDA) approved Harvoni in the third quarter of 2014. It carried a hefty price tag –up to $90,000 for a 12-week course of treatment—the standard treatment duration for most people with HCV genotype 1. The side effects are considered low especially compared to the previous therapies that contained interferon. It was a breakthrough in the treatment of hepatitis C for people with genotype 1—an all-oral treatment that consisted of a combination of sofosbuvir and ledipasvir combined into one pill taken once-a-day that cures up to 100% of people who take the combination. Truly Harvoni is a miracle drug. It is hard to say with certainty the exact price of Harvoni since the price has been negotiated with various payers, but regardless the price is high. There has been much negative press, congressional hearings, protests and more attention paid to the cost than any other medicine this year. In November 2015, the FDA approved a new indication for Harvoni for the treatment of genotype 4,5,6 and those coinfected with HIV. Also, the new indication includes treatment with ribavirin for genotype 1 treatment-experienced patients with cirrhosis.

Viekira-Pak was approved December 2014, and the price tag was a little under Harvoni—$84,200. It did not generate as much negative press or sale of prescriptions. They did, however, have an excellent community education/navigation program.

The price of the drugs set the stage for a tug of war between patients, and medical insurance coverage of the drug and Medicaid. Many insurance companies and almost all state Medicaid programs were only approving coverage for people with the most severe HCV disease (severe fibrosis, cirrhosis). At first, Gilead was picking up the gap in insurance coverage with their patient assistance program, but after awhile, Gilead stopped covering the denials deciding that insurance companies and state Medicaid programs needed to start covering the medications.

Exclusivity Deals

Another issue with the price was the exclusivity deals between the pharmaceutical companies (Gilead/AbbVie) and insurance companies/payers to reduce the costs of the medications. The good news is that it lowered the cost of the drugs. However, it set a precedent to have treatment decisions made by corporations rather than a trained medical provider who has years of medical experience to guide an important healthcare decision.

In all of this guess who loses?

Patients of course!

Medicaid and CMS

There is some promising news—towards year-end, the Centers for Medicare and Medicaid Services (CMS) issued a notice to state Medicaid programs that they were breaking the law and should lift the restrictions placed on access to HCV medications. The restrictions limited access to HCV medications to only those who had severe fibrosis or cirrhosis or those with a serious condition such as diabetes, cryoglobulinemia, and other types of extrahepatic manifestations. It is too soon to tell what overall effect the CMS notice will have, but some states are starting to comply.

The denials by insurance companies and Medicaid lead to many lawsuits in 2015. As of the date of this publication there have not been any judgments made but 2016 should provide some news.

Generic Sofosbuvir

Gilead has licensed sofosbuvir and ledipasvir to some countries (India, Pakistan and Egypt) to make a generic version. Daclatasvir is another drug that is produced as a generic drug. The countries that manufacture the generic drugs are responsible for making sure the quality is chemically the same. There are other sources of generic sofosbuvir, ledipasvir, and daclatasvir, but there may be quality assurance issuances. Be sure to do your research – there are some websites and blogs that verify the accuracy of the chemical makeup of the generic drugs—the old saying applies here: buyer beware, or buyer be careful. Generic drugs are going to be one of the most important strategies to eliminate HCV worldwide. There will be a need for drugs that are much cheaper to treat it especially in developing countries.

Updated AASLD/IDSA Guidance

Finally, the American Association for the Study of Liver Disease and Infectious Disease Society of America has issued guidance that “evidence clearly supports treatment for all HCV infected persons, except those with limited life expectancy (less than 12 months) due to non–liver-related comorbid conditions.”

Acute Outbreaks of HCV 2015

Outbreaks of acute hepatitis C among people who inject drugs continues to spread. The highest hit areas were the Appalachian areas in the U.S. The last report (2013) from the Centers for Disease Control and Prevention (CDC) listed acute cases as 29,700 (range 23,500 – 101,400). A study titled “Underascertainment of Acute Hepatitis C Virus Infections in the U.S. Surveillance System: A Case Series and Chart Review,” by S Onofrey, MPH et. al., published in the Annals of Internal Medicine, estimated that only 1% of the real number is reported to the CDC. Needle exchange was mostly established after the outbreaks. If only needle exchange were established beforehand it would have prevented the outbreaks in the first place!

2015 FDA Approval

Daklinza (daclatasvir) in combination with sofosbuvir was approved by the Food and Drug Administration to treat HCV genotype 3. Both drugs are taken once-a-day for 12 weeks. In clinical trials, the cure rates were 98% for treatment naïve patients without cirrhosis; 58% for treatment naïve patients with cirrhosis. In treatment-experienced patients without cirrhosis, the cure rate was 92%; in treatment-experienced patients with cirrhosis, the cure rate was 69%.

Technivie (ombitasvir, paritaprevir, and ritonavir) plus ribavirin to treat treatment naïve genotype 4 patients was approved by the FDA. The cure rates are up to 100%.

2016 FDA Approvals

Some good news! Next year—actually the end of January Merck’s combination of elbasvir and grazoprevir—brand name Zepatier will be approved by the FDA. The cure rates are up to 99% in genotype 1,4 and 6. Merck applied to the FDA for marketing approval earlier in the year.

Phase 3 clinical trials sofosbuvir plus velpatasvir were completed, and Gilead applied for marketing approval to the FDA later in 2015. The cure rates for patients treated with sofosbuvir plus velpatasvir (GS-5816) with genotypes 1 through 6 were up to 97% to 100%. Gilead has applied for marketing approval to the FDA. The combination will be approved in 2016. This is good news for all genotypes but especially those with genotype 3 who had cirrhosis the cure rate was 91%.

Resistance-associated Variants (RAVs)

RAVs occur naturally, during treatment (viral breakthrough) and after treatment (relapse) with direct acting antiviral medications (DAA—protease, polymerase, NS5A inhibitors). RAVs may lead to treatment of a DAA medication not working. The guidelines for testing vary, but the AASLD/IDSA Guidance has guidelines for testing for RAVs before retreatment. Treating with a combination of different DAA drugs that include a one or more pan-genotypic drugs is also an effective strategy.

Pan-genotypic Drugs

Drugs that have antiviral properties against all of the genotypes are called pan-genotypic. These types of drugs have come into prominence this year and will continue to be highly sought after to treat hepatitis C. Pan-genotypic drugs, when developed to be highly effective against all genotypes, may eliminate the need for the expensive genotype test, treat people with multiple genotypes and help treat people with resistance-associated variants (RAVs).

The FDA issued a warning this year that Viekira Pak and Technivie can cause severe liver injury in patients with advanced liver disease. As a result, AbbVie has added new information to their package label. If you are a patient taking the one of the AbbVie combinations, talk to your medical provider if you have any concerns.

New Cell Culture

The Journal Nature released a study by led by scientists from The Rockefeller University who identified a human cell that can replicate the hepatitis C virus. This will help science understand the hepatitis C virus and optimize hepatitis C treatment including treating people who develop RAVs.

2015 has brought a lot of good times for people with hepatitis C – at least, those who were treated and cured. If you fall into the group of individuals who were denied HCV treatment by insurance companies or Medicaid it has been a frustrating and depressing year.

What has been very positive this year for me in advocacy is to see so many advocates working for patients. You may not hear or see them, but they are out there working tirelessly to help people with hepatitis C. Many are working for access to treatment. HCV Advocacy is finally coming of age, and it is reassuring to see so many new people in HCV advocacy. There are also a large number of individuals who work in HIV who are turning their energies to HCV advocacy.

So if you think no one has your back know that there are hundreds of people who are working hard to try to get you access to treatment and other services. If you see them, or they contact you ---thank them. Most people who work in advocacy don’t expect it and ‘thank you’ sure feels good when gratitude comes their way.

Top News – 2015 —Alan Franciscus, Editor-in-Chief