Harvoni Gains More Differentiation With Updated Labeling

It would be difficult to accuse Gilead Sciences Inc. of complacency in hepatitis C, as the virology powerhouse announced an FDA supplemental approval Feb. 16 that adds language for patients with advanced liver disease to the Harvoni label, a clear edge over competing products from Merck & Co. Inc. and AbbVie Inc.

The new language adds patients with genotype 1 HCV infections and Child-Pugh B or C disease (decompensated or later-stage cirrhosis) to the labeling for the fixed-dose combination pill. In addition, labeling now includes genotype 1 or 4 patients who've had a liver transplant and either are non-cirrhotic or have compensated (early-stage) cirrhosis, also known as Child-Pugh A disease. In both cases, the new language specifies a 12-week regimen of Harvoni combined with ribavirin.

This is the second label expansion for Harvoni (sofosbuvir/ledipasvir) in about three months, as Gilead announced Nov. 12 that FDA approved the drug to treat genotypes 4, 5 and 6 of the virus, as well as genotype 1 patients who are co-infected with HIV. That update also included a 12-week course of Harvoni plus ribavirin as an alternative therapy to the 24 weeks included in the drug's original October 2014 label for genotype 1 patients with compensated cirrhosis.

In an email exchange, Gilead noted that Harvoni now is the first HCV drug approved for genotype 1 liver transplant recipients with compensated cirrhosis. It also is the first endorsed for a 12-week course of therapy in genotype 4 liver-transplant recipients with compensated cirrhosis. Merck's Zepatier (grazoprevir/ledipasvir), approved Jan. 28, includes labeling for 16 weeks of therapy for the latter subgroup (Also see "Merck's Biggest Impact With Zepatier Approval May Be On HCV Pricing" - Pink Sheet, 1 Feb, 2016.).

More importantly, Harvoni now is explicitly approved to treat HCV-infected patients with decompensated cirrhosis, while Zepatier and AbbVie's Viekira Pak (ombitasvir/paritaprevir/ritonavir tablets; dasabuvir tablets) are contraindicated for those subpopulations. Originally, Viekira was contraindicated for patients with Child-Pugh C disease while not recommended to treat patients with Child-Pugh B, but an FDA postmarket drug safety communication Oct. 22 revised the label to contraindicate for both subpopulations (Also see "AbbVie In Hot Seat Over HCV Drugs' Serious Liver Injury Risk" - Pink Sheet, 22 Oct, 2015.).

Sharper Contrast To Merck, AbbVie

Morningstar analyst Karen Andersen told "The Pink Sheet" DAILY that this labeling change gives Gilead a further advantage in a market it already dominates, with market share estimated at about 90% for Harvoni and Sovaldi (sofosbuvir).

"Even though the patient populations we’re talking about are small, I think this puts the safety differences between Harvoni and competing regimens (Zepatier and Viekira) in sharper contrast – Harvoni is safe and effective for genotype 1 patients with the most advanced cases of liver disease (Child-Pugh B and C)," she said in an email.

Such an advantage could prove very valuable to Gilead, which spent much of its fourth-quarter earnings call explaining why its HCV franchise saw a 26% decline in sales domestically compared to fourth quarter 2014 revenues (Also see "Gilead HCV Sales Decline In US, But Offset By Global Growth" - Pink Sheet, 2 Feb, 2016.). That US market softness, however, was more than offset by strong sales growth both in Europe and Japan, enabling the Foster City, Calif.-based firm to report a 27% global sales increase year-over-year for the franchise, to nearly $4.9bn.

Asked about Gilead's strategy for detailing the labeling update, the firm said only, "As part of our ongoing education efforts, Gilead will work to ensure health care providers have the information they need to make the best treatment decisions for their patients."

On the quarterly call, Paul Carter, Gilead's executive VP of commercial operations, noted that about 400,000 US HCV patients had been treated since Sovaldi's launch in 2013, with about 90% of that total estimated to have been treated with a sofosbuvir-based regimen. That means about 3m HCV-infected patients remain uncured domestically, according to Centers for Disease Control and Prevention data, with roughly half of those not yet diagnosed.

"Long-term education and awareness efforts to increase rates of diagnosis and the flow of HCV-infected patients into treated care are important and will play out over many years, as we know from our experience in HIV," Carter said.

Patient Base Replenishes … So Far

Gilead creates its own proprietary statistics, using three different data sources, he added, to gain a clear picture of the US HCV patient base. About 30,000 patients a month are diagnosed with HCV and entered into care, although that does not necessarily mean starting a curative antiviral regimen, Carter said.

"So they are diagnosed with HCV and they are registered with the treater," he said. "If we do the math on that, clearly, that's 360,000 patients coming into treatment a year. And we are seeing treatment levels a lot lower than that. And what that speaks to is the types of patients are different amongst that 360,000-member group and their pathway to actual treatment varies considerably. But there does appear – again doing the math and assuming the research is correct – that there is a line at the door of patients that still need to be treated and are accessible."

Carter also said that Gilead's experience shows that Harvoni and Sovaldi continued to be well-positioned competitively, despite some managed care providers' expectations that the introduction of multiple competing products might result in a commoditization of the space. The Feb. 16 label additions should only increase that edge.

"What we've seen, fortunately, with Harvoni, in particular, is the real-world data have really strengthened its position and people's understanding of what that product is," the exec said. "It cures people with an incredibly high SVR rate, and the safety profile has been extremely good and in line [with], if not better than its label."

"That hasn't been the case of competitive products so far," Carter continued. "In fact, we've seen safety warnings added to labels and we've seen a differentiation. And that has played out in the market. So, I think as we see a new competitor [Merck's Zepatier] coming into the market now, payers are really thinking this through. There [aren't] any instinctive reactions. People are being very thoughtful and we know this because we have very close discussions with the managed care main players and we are working with them as they think through this."