Updated interim phase II data showing that a combination of Achillion Pharmaceuticals Inc.'s NS5A inhibitor, ACH-3102, and Sovaldi (sofosbuvir, Gilead Sciences Inc.) cleared hepatitis C virus (HCV) in 100 percent of 12 genotype 1 patients after just six weeks of treatment – the shortest of any two-drug, direct-acting antiviral regimen, the company said – pushed shares (NASDAQ:ACHN) up 7.8 percent to $11.66 on Monday.

Patients similar to those tested now generally take an eight to 12 week course of currently approved medicines, such as Gilead's Harvoni (sofosbuvir and ledipasvir), Abbvie Inc.'s Viekira Pak (ombitasvir, paritaprevir, ritonavir and dasabuvir), or Sovaldi with peginterferon alfa and ribavirin.

"Our goal is to deliver short duration, widely accessible treatments to all HCV patients," said Achillion president and CEO Milind Deshpande "Given the exceptional profile of ACH-3102, we will now be evaluating four- and six-week treatment durations that leverage all of our HCV assets including ACH-3102, ACH-3422 and sovaprevir," the company's NS3/4A protease inhibitor.

Deshpande is also upbeat about the ability of shorter treatment regimens to improve adherence, a key area of friction in nearly all treatments for chronic disease. "Real world studies have shown that patient compliance can be increased with shorter duration therapies," he told BioWorld Today. "Therefore, we would hope to see similar outcomes take place in HCV with shorter treatment duration regimens that can provide high cure rates."

The ongoing open-label trial is a randomized, partial-crossover study to evaluate the efficacy, safety and tolerability of eight- and six-week regimens of the ACH-3102/Sovaldi combination given once daily. It enrolled 18 patients at first, seven genotype 1a patients and five genotype 1b patients. Twelve weeks after the completion of therapy, all 12 patients in the six-week trial arm achieved SVR12, independent of baseline viral load, gender and their IL28B genotype, a factor that impacts patients' immune response to HCV infection. Six observational patients from the six-week arm, plus six newly enrolled patients then crossed over to an eight-week treatment arm, in which all 12 patients achieved SVR24. The combination was well tolerated with no serious adverse events, no discontinuations due to adverse events, and no clinically significant laboratory or ECG abnormalities, the company said.

The combination appeared to work even in patients with a high baseline viral load. Mean baseline HCV RNA viral load was 10 million (7 log10) IU/ml, with a range of 2 million (6.23 log10) to 97 million (7.99 log10) IU/ml, including seven patients with baseline HCV RNA viral load exceeding 6 million (6.78 log10) IU/ml.

"The achievement of 100 percent SVR12 after six weeks of treatment with a dual NS5A-nucleotide regimen, even in patients with high baseline viral load who would otherwise require extended duration treatments, supports our belief that ACH-3102 can unleash the potential of this combination to drive down treatment duration," said David Apelian, Achillion's chief medical officer.

Whereas previous studies with ACH-3102 used a loading dose on the first day of treatment, the phase II studies did not. That, along with the ability to achieve high SVR rates after only eight-week and six-week regimens in a ribavirin-free regimen, provided significant insight into the role ACH-3102 can play in a NS5A/nucleotide inhibitor regimen, the company said. (See BioWorld Today, Feb. 4, 2015.)

Next, New Haven, Conn.-based Achillion is preparing to initiate its SPARTA phase II program, a study to evaluate short treatment durations with a combination treatment of its own making, including once-daily regimens of ACH-3102 and its nucleotide inhibitor ACH-3422, with or without sovaprevir (ACH-1625), for treatment-naïve genotype 1 HCV patients. It's also exploring regimens that could potentially shorten the amount of times patients need take Sovaldi in combination with ACH-3102 and sovaprevir.

The ongoing study is pairing a 50-mg dose of ACH-3102 with 400-mg dose of Sovaldi in an interferon-free, ribavirin-free regimen in previously untreated patients. Its primary endpoint is sustained viral response 12 weeks after completion of therapy.

Even with positive clinical data, Wells Fargo senior analyst Brian Abrahams suggested that payer leverage in the hot HCV market is compressing pricing and profit potential. In a note to clients Monday, he said that Gilead's steep discounting of Harvoni and Sovaldi, expected to reach 46 percent for the year ahead, is substantially higher than expected, "a negative development for HCV companies" that will require them to reach increasing volumes of patients to generate robust revenues.

Achillion's Deshpande isn't concerned at this point. "Achillion's development plans have remained steadfast in its commitment to advancing commercially competitive, short-duration, ribavirin-free treatments for HCV," he said. "The recent market dynamics impact the current participants, similar to the commercial decisions made during the launch and sales of telaprevir and boceprevir, but do not have meaningful impact of future players in the HCV market."

Achillion's shares have risen 266.8 percent from a year ago.