HCV Notes: NICE Nod To Gilead's Epclusa; Achillion, AbbVie Data Updates

The UK's health care cost-assessment body finds Gilead's newest combo, Epclusa, cost-effective in most HCV settings. J&J/Achillion now have 12-week SVR data for six-week treatment regimen, and AbbVie builds support for an eight-week regimen for Viekirax.

It's yet another win for Gilead Sciences Inc. in hepatitis C as the UK's National Institute for Health and Care Excellence (NICE) judges the specialty pharma's latest fixed-dose combination Epclusa (sofosbuvir/velpatasvir) cost-effective for just about all HCV-infected patients.

On Sept. 23, NICE recommended Epclusa as a treatment option for all six genotypes of HCV, with the caveat that it is not recommended for treatment-naïve, non-cirrhotic genotype 2 patients who are able tolerate interferon-based therapy. In that one specific setting, interferon-inclusive regimens are viewed more cost-effective than Epclusa.

The European Medicines Agency recommended Epclusa for approval on May 27, along with Merck & Co. Inc.'s Zepatier (grazoprevir/elbasvir). (Also see "Gilead's Epclusa And Merck's Zepatier Hep C Combos Get EMA backing" - Scrip, 31 May, 2016.) Following a confidential price negotiation with Merck, NICE recommended Zepatier, with or without ribavirin, on Sept. 8 for treatment of patients infected with genotypes 1 and 4 of the virus. (Also see "NICE Backs Hep C Drug Zepatier After Merck Offers Price Discount" - Scrip, 8 Sep, 2016.) The recommendation of Epclusa also allows for the inclusion of ribavirin in the therapeutic regimen.

NICE said its appraisal committee determined that Epclusa was clinically and cost effective, and should be "routinely available" to patients treated under the National Health Service. Particularly, NICE recognized a need for HCV therapy with fewer adverse side effects and for patients with genotype 3 of the virus, who comprise about 44% of the patient base.

Gilead and NICE have agreed to a confidential discount to the NHS for Epclusa. The listed cost for a 12-week course of therapy with the fixed-dose combo is £38,890 (about $50,400), which would increase to about £40,000 if ribavirin was included in the regimen.

This is the third NICE okay for an exclusive Gilead HCV regimen, and the fourth overall for HCV regimens including a Gilead drug. In February 2015, it recommended sofosbuvir (Sovaldi) with peginterferon-alfa and/or ribavirin for all genotypes; in November 2015, it recommended the fixed-dose combo of sofosbuvir and ledipasvir (Harvoni) to treat genotypes 1 and 4 of the virus; and in November 2015, it recommended co-administration of sofosbuvir and Bristol-Myers Squibb Co.'s daclatasvir (Daklinza), with or without ribavirin, to treat genotypes 1, 3 and 4. The last recommendation also included the option of substituting interferon for sofosbuvir.

Achillion/J&J Regimen Achieves SVR12 With Six Weeks Of Therapy

Updating promising interim data unveiled on Sept. 9, Johnson & Johnson and Achillion Pharmaceuticals Inc. reported that their three-drug regimen achieved a 100% (20/20) rate of sustained virologic response (SVR) at 12 weeks after the end of a six-week regimen – the companies previously had reported that the regimen had produced SVR at four weeks after the end of treatment for all 20 patients in one cohort of a Phase II trial. (Also see "J&J, Achillion Could Set Six-Week Treatment Paradigm In HCV" - Scrip, 9 Sep, 2016.)

The regimen, which comprises J&J's protease inhibitor Olysio (simeprevir) 75 mg daily, its experimental nucleoside polymerase inhibitor AL-335 800 mg daily and Achillion's NS5A inhibitor odalasvir (ACH-3102) 50 mg every other day, achieved SVR12 in genotype 1 patients in interim data from a four-cohort trial presented Sept. 23 in Paris at the European Association for the Study of the Liver's Special Conference: New Perspectives in Hepatitis C Infection – The Roadmap for Cure.

Market analysts said these data, if replicated in a Phase III trial, could yield a regimen competitive with current market leaders, including Gilead's various direct-acting antiviral products, but warned that concerns about one serious cardiovascular adverse event seen in the study would have to be ameliorated further. The cardiac SAE occurred in another cohort of the study testing an eight-week daily regimen of AL-335 400 mg, odalasvir 50 mg and Olysio 100 mg, which yielded a 100% SVR rate (20/20) 24 weeks after the conclusion of therapy.

One patient in that cohort experienced a Mobitz Type 1 second-degree atrioventricular blockage, which was detected by echocardiogram, but resolved with discontinuation of treatment. Later review of the patient, who required no other therapeutic intervention, found no clinical or echocardiographic abnormalities.

J&J is planning a Phase IIb study testing six- and eight-week courses of a daily regimen of odalasvir 25 mg, AL-335 800 mg and Olysio 75 mg in treatment-naïve and treatment-experienced, non-cirrhotic HCV patients with genotypes 1, 2, 4, 5 and 6. Concurrently, the pharma also will run a Phase IIa study testing the same regimen in genotype 3 patients with or without cirrhosis.

The EASL presentation provided further information on the SAE patient, whose reaction was deemed probably related to odalasvir and possibly related to Olysio and/or AL-335. In a Sept. 23 note, Jefferies Equity Research analyst Brian Abrahams said that while the SAE was asymptomatic and did not lead to ECG changes, it "did seem to track temporally with the treatment, potentially suggesting causality – and the safety bar in HCV is very high."

A drug-drug interaction finding had led to odalasvir being dosed every other day in this one cohort of the trial, Abrahams added, so the safety, efficacy and pharmacokinetics of the go-forward 25 mg daily dose of that compound will be a crucial factor for the success of the succeeding studies. He added that J&J will also need to show efficacy in more difficult-to-treat patients to threaten Gilead's market supremacy and wondered how much of a competitive edge a six-week therapeutic duration would be, considering that Harvoni and Epclusa are approved for eight-week therapy in some patients.

More optimistic was analyst Liisa Bayko of JMP Securities, who wrote Sept. 23 that "a shorter duration (six-week regimen) will differentiate this product and could help the combination gain a greater piece of the global HCV market."

AbbVie Postmarket Data Show Eight-Week Efficacy In G1b Patients

Also at the EASL meeting, AbbVie Inc. presented Phase IIIb data for its fixed-dose combo product, marketed as Viekira Pak in the US, that showed a 98% SVR12 rate (160/163) for treatment-naïve, non-cirrhotic, genotype 1b patients treated for eight weeks. The Chicago-area pharma says this could make the regimen more competitive in Europe, where an estimated 47% of the 9m HCV-infected patients have the genotype 1b strain.

The regimen, marketed as two products Viekirax (ombitasvir/paritaprevir/ritonavir) and Exviera (dasabuvir) in Europe, currently is approved in the EU for a 12-week therapeutic duration in genotype 1b patients. (The US product, Viekira Pak, combines all four compounds under a single brand name, although it is dosed as two tablets.)

The data from AbbVie's GARNET study supporting use of an eight-week regimen were included in the EASL Recommendations on Treatment of Hepatitis C presented at the meeting. A total of 166 patients were enrolled in the open-label, single-arm study, but three were excluded after they were discovered not to have genotype 1b virus. One hundred and sixty patients achieved SVR12; of the three treatment failures, two experienced post-treatment relapse, while one subject was discontinued due to non-compliance, AbbVie said.