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AbbVie's Viekira "3D" Combo for Hepatitis C Wins FDA Approval

The U.S. Food and Drug Association this week approved AbbVie's Viekira Pak for people with genotype 1 chronic hepatitis C, including patients with compensated cirrhosis. The regimen -- formerly known as "3D" -- consists of the HCV NS3/4A protease inhibitor paritaprevir, a ritonavir booster, and the NS5A inhibitor ombitasvir in a once-daily coformulation, taken with the twice-daily non-nucleoside HCV NS5B polymerase inhibitor dasabuvir.

The interferon-free Viekira regimen has demonstrated very good efficacy in Phase 2 and 3 clinical trials enrolling more than 2300 participants in 25 countries, with 12-week post-treatment sustained virological response (SVR12) rates in the 90% to 100% range. It has been shown to be effective in traditionally hard-to-treat populations includingHIV/HCV coinfected people, patients with cirrhosis, and liver transplant recipients.

Viekira Pak is the only FDA-approved regimen that contains 3 distinct mechanisms of action that work together to attack HCV at 3 separate stages of its lifecycle to inhibit it from reproducing, according to an AbbVie press release announcing the approval.

The FDA approved Viekira Pak only for patients with HCV genotype 1, though it has also demonstratedeffectiveness against genotype 4 in the PEARL-I trial.

The recommended Viekira Pak dosing regimen is 2 ombitasvir/ paritaprevir/ritonavir tablets (each 12.5/75/50 mg) in the morning, 1 dasabuvir tablet (250 mg) in the morning, and 1 dasabuvir tablet in the evening, all taken with food.

The recommended duration of treatment is 12 weeks for most people, with the exception of patients with harder-to-treat HCV subtype 1a and cirrhosis, who should be treated for 24 weeks. Liver transplant recipients with moderate fibrosis (Metavir stage F2 or lower) should be treated for 24 weeks regardless of HCV subtype. The Viekira regimen is not recommended for people with decompensated cirrhosis or moderate or worse liver function impairment (Child-Pugh class B or C).

People with genotype 1a or cirrhosis (or both) should take the Viekira combo with weight-based ribavirin, a drug that helps prevent relapse. Those with easier-to-treat genotype 1b without cirrhosis do not need ribavirin. In clinical trials, cure rates were typically statistically similar with or without ribavirin, though ribavirin appeared to boost sustained response in harder-to-treat patients.

Recommendations are the generally the same for HIV/HCV coinfected and HIV negative hepatitis C patients. However, individuals taking ritonavir-boosted HIV protease inhibitors will need to adjust their doses. It will be difficult to use Viekira with ritonavir-containing antiretroviral coformulations (this presumably also applies to the booster cobicistat).

The Viekira regimen is generally safe and well-tolerated. The most common side effects reported in clinical trials were fatigue, nausea, weakness, insomnia, pruritus (itching), and rash. ALT elevation is listed as a precaution, though it occurred in only about 1% of clinical trial participants. Adding ribavirin can lead to anemia. Ribavirin also increases the risk of birth defects and should not be used by women who are or wish to become pregnant or their male partners.

What About Cost?

Viekira Pak will mainly compete with Gilead Science's recently approved sofosbuvir/ledipasvir coformulation, Harvoni.

Harvoni is more convenient, requiring just 1 pill once-daily, and does not have such an extensive list of drug interactions and contraindications as Viekira. It also does not require boosting with ritonavir, which can add to side effects (though this does not appear to be a significant problem with short-term hepatitis C treatment, compared with long-term antiretroviral therapy for HIV).

Many patients, providers, and payers had hoped AbbVie would compete on cost, but the announced price of $83,300 for a 12-week course is higher than many expected. Harvoni is still more expensive -- at $94,500 for a 12-week course -- but it does not require ribavirin (about $500 for 12 weeks) and many easier-to-treat patients can be cured in 8 weeks, as shown in the ION-3 trial. A shorter 8-week regimen may also be enough for some patients treated with the Viekira combo, but this does not have as much supporting evidence.

AbbVie has a Patient Assistance Program that provides medication at no cost. A co-pay assistance program will be available for commercially insured people using Viekira Pak; the company said in its press release that out-of-pocket costs for eligible patients could be as little as $5.00 per month. AbbVie has launched a patient support program called proCeed that will provide a broad range of patient support options (www.viekira.com or 1-844-2-PROCEED).

But AbbVie's most aggressive move to date is making deals with specific payers to offer deep discounts.

Pharmacy benefits manager Express Scripts announced that it has negotiated a multi-year deal in which Viekira Pak will be the exclusive treatment option for genotype 1 hepatitis C patients covered by its national preferred formulary; it did not state the discounted price. Express Scripts added that it will provide Viekira Pak regardless of symptoms or disease progression, at a time when many insurers, public payers, and national health systems are restricting treatment to patients with advanced liver disease in an effort to control costs.

"Pharmaceutical innovation must be rewarded based on the value it brings to patients and payers," said Steve Miller, MD, senior vice president and chief medical officer of Express Scripts. "This agreement marks a fundamental change in how sustainable access and affordability will be delivered to hepatitis C patients."

The AbbVie/Express Script deal breaks new ground in the arena of pharmaceutical price competition. While this agreement could potentially allow many more hepatitis C patients to receive prompt treatment, it also sets a precedent of payers -- rather than doctors -- making blanket decisions about treatment options on the basis of price.

12/22/14

Sources

Food and Drug Administration. FDA approves Viekira Pak to treat hepatitis C. News release. December 19, 2014.

R Klein, K Struble, and S Morin, FDA. FDA Hepatitis Update: VIEKIRA Pak. December 19, 2014.

AbbVie. AbbVie Receives U.S. FDA Approval of Viekira Pak (ombitasvir/paritaprevir/ritonavir tablets; dasabuvir tablets) for Treatment of Chronic Genotype 1 Hepatitis C. Press release. December 19, 2014.

Express Scripts. Express Scripts and AbbVie Make Hepatitis C Cure Available to Millions of Patients in Need. Press release. December 22, 2014.