PART TWO OF TWO [Part One was published 8/4/17]

 Direct-Acting Antiviral Drugs (DAAs)   

The FDA approved the first DAAs—Incivek® (telaprevir) and Victrelis® (boceprevir)—in 2011. Before then, the conventional hepatitis C virus (HCV) treatment for HCV genotype 1 consisted of peginterferon (often called just interferon) and ribavirin, a combination known as PR therapy. PR therapy required a 48-week course and had a “cure” rate, measured by sustained virologic response (SVR) and defined as having no HCV ribonucleic acid in the blood 24 weeks after a treatment, of about 50 percent.

Besides a less-than-ideal success rate, tolerance was a major problem with PR therapy. A sizeable number of patients could not take interferon because of adverse effects that ranged from flu-like symptoms, dry mouth, insomnia, weight loss, and diarrhea, on the mild end, to a persistent sore throat, an unusually slow, fast, or pounding heartbeat, vomit that looked like coffee, bloody diarrhea, and numbness and tingling in the extremities, on the severe end.

Ribavirin, the R in “PR,” is an antiviral drug that is not direct-acting. It is used today in combination with a DAA, in particular, with Harvoni in more seriously ill patients.

The SVR reached 75 to 80 percent with the DAAs, Incivek and Victrelis, but patients had to be on PR therapy simultaneously and had to dose every seven to nine hours for periods up to 48 weeks. Both drugs were discontinued after Sovaldi and Harvoni arrived.

Another DAA, Olysio® (simprevir), was introduced in 2013 to be used in combination with PR therapy. In late 2014, the FDA approved Olysio’s use in combination with Sovaldi, and it remains on the market.

Gilead’s chief competition comes from Abbvie, a global biopharmaceutical company that markets HCV-drug packages called Viekira Pak®, which also debuted in late 2014 and was priced competitively, and Viekira XR™, a 2016 improvement on the Pak. Both Viekira products consist of the DAAs ombitasvir/paritaprevir/ritonavir “co-packed” with the drug, dasabuvir, and treat only HCV genotype 1. For the essential details about Viekira Pak and Viekira XR, such as their SVR and common adverse effects, please consult your physician.

Facts of Harvoni

Much is known now about Harvoni treatment that was not known when it first came on the market. The FDA has approved its use in infections with HCV genotypes 1,4, 5, and 6; in HCV/HIV-1 coinfections; in HCV genotype 1- and 4-infected liver-transplant recipients, who don’t have cirrhosis; and in genotype 1-infected patients with decompensated cirrhosis, including those who have had liver transplants.

Harvoni is taken with ribavirin when the patient has cirrhosis or has undergone previous treatment. Patients who are being treated for the first time are known as treatment-naïve; those who are being retreated, usually after a failure with PR therapy, are treatment-experienced. Those who have had a transplant must take both drugs.

Patients who still have an undetectable HCV viral load 12 weeks after finishing treatment—known as SVR12—are considered cured. 

Harvoni is generally well tolerated, with the most common adverse effects being fatigue, headache, and weakness. Serious adverse effects have been associated with its use, however, including:

*A reactivation of hepatitis B virus: If you have ever had HBV, the virus could become active again and be more resistant.

*Bradycardia (slow heart rate): If you take amiodarone for atrial fibrillation or another heart problem, Harvoni may cause your heart to slow excessively, leading to the need for a pacemaker or to death.

Harvoni can raise levels of the HIV drug tenofovir, so people taking these drugs together should have their kidney function checked regularly. It also can interact poorly with certain tuberculosis medications, psychiatric drugs, and cholesterol-lowering drugs. Talk to your physician about all of your medical conditions and medications before you start Harvoni treatment. You should not take Harvoni with rosuvastatin (Crestor®) or herbal products containing St. John’s wort. (The list of interactions with Harvoni is likely to grow as the patient pool expands.)

Help with Costs

Since Harvoni debuted in 2014, Gilead has agreed to price discounts and rebates as part of Medicare, through Part D, and Medicaid, and has made available to patients with commercial insurance and to “cash-pay” patients, who either have no insurance or who have commercial insurance that does not cover Harvoni, co-pay coupons to lower the cost. See https://www.harvoni.com/support-and-savings/co-pay-coupon-registration for details.

Coverage for a Harvoni prescription varies according to the payer, of course, but, generally speaking, you can expect a hefty out-of-pocket payment. If your physician agrees, you might consider waiting to start a course of treatment. It’s possible that costs will go down with increased competition (especially from Abbvie) or shortened treatment courses.

Be sure to read your health insurance policy’s fine print so you understand your medication coverage program; then negotiate directly with your insurance company or appeal any denial of coverage. Harvoni treatments are “medically necessary” and arguably save money over the long run.

Your doctor may be able to recommend programs that will help you if you need assistance with payment. Start with him or her. The nonprofit Patient Access Network Foundation helps uninsured or underinsured people pay for part of the cost of Harvoni treatment. Contact PANF at www.panfoundation.org or 866-316-PANF (7263).

You should not start Harvoni treatment if you are not sure you can complete it. Incomplete therapy can lead to a high rate of relapse of the HCV and the risk that it will harbor resistance that could compromise a future course of treatment. 

***

I explored HCV transmission (blood-to-blood) and diagnosis in Part One of this blog. The CDC recommends that the following individuals be tested for HCV infection:

*Persons born from 1945 to 1965

*Persons who have ever injected illegal drugs, including those who injected only once many years ago

*Recipients of clotting factor concentrates made before 1987

*Recipients of blood transfusions or solid organ transplants before July 1992

*Persons with known exposures to HCV, such as health care workers who have had needlesticks involving HCV-positive blood and recipients of blood or organs from a donor who later tested HCV-positive

*All persons with HIV infection

*Patients with signs or symptoms of liver disease, such as abnormal liver enzyme tests

*Children born to HCV-positive mothers (children should not be tested until they are at least 18 months old)

The CDC is now targeting the baby boomers because it believes not enough of them are coming forward to be tested. Clearly, if you know that you could not have exposed yourself to HCV-contaminated blood, you need not rush to get tested. If you have any doubt, please speak to your physician. Peace of mind is a key component of your health.

Ann, 8/7/17