Dolutegravir Combo Beats Atripla in Phase 3 Study of Previously Untreated HIV Patients

ViiV Healthcare and Japan's Shionogi announced this week that a combination antiretroviral regimen containing the experimental integrase inhibitor dolutegravir suppressed HIV viral load as well as the popular Atripla (efavirenz/tenofovir/emtricitabine) coformulation in treatment-naive individuals, but with fewer side effects.

Integrase inhibitors work by preventing HIV from inserting its genetic material into a host cell's chromosomes, a necessary step in viral replication. Integrase inhibitors are a well-tolerated class of antiretrovirals, perhaps because they do not interfere with essential host cell functions. As previously reported, the SPRING-2 study found that dolutegravir (formerly S/GSK1349572) was non-inferior to the sole approved integrase inhibitor, raltegravir (Isentress).

Below is an edited excerpt from a Shionogi-ViiV press release describing the study and its findings. The data are expected to be presented at upcoming medical meetings.

Shionogi-Viiv Healthcare Announces Positive Initial Data From Phase III Study of Dolutegravir-Based Regimen vs Atripla in HIV

London, United Kingdom --  July 11, 2012 --Shionogi-ViiV Healthcare LLC today announced that initial results have been received from the Phase III SINGLE (ING114467) study of the investigational integrase inhibitor dolutegravir in treatment-naive adults with HIV-1.

The study demonstrated superiority of the dolutegravir-based regimen compared to the single tablet regimen Atripla. At 48 weeks, 88% of study participants on the dolutegravir regimen were virologically suppressed (<50 copies/mL) vs. 81% of participants on the single tablet regimen Atripla [difference and 95% CI; 7.4% (+2.5% to +12.3%); difference in the primary endpoint was statistically significant, p=0.003]. Differences in efficacy were primarily driven by a higher rate of discontinuation due to adverse events on the Atripla arm. The SINGLE study was designed to demonstrate non-inferiority of the dolutegravir-based regimen versus Atripla, and the primary analysis met this criterion. Statistical superiority was concluded as part of a subsequent, pre-specified testing procedure.

SINGLE is an ongoing double blind, double dummy study designed to compare the efficacy and safety of two antiretroviral regimens: dolutegravir 50 mg plus abacavir/lamivudine (Kivexa/Epzicom) versus Atripla (tenofovir/emtricitabine/efavirenz). The primary endpoint was the proportion of study participants with undetectable HIV-1 RNA (<50 copies/mL) at 48 weeks; 414 treatment-naive study participants were randomizedand exposed to the dolutegravir-based regimen and 419 to the Atripla arm. Overall, 2% of subjects on the dolutegravir-based regimen discontinued due to adverse events vs. 10% of those receiving the Atripla regimen.The most common drug related adverse events on Atripla were in the nervous system System Organ Class (reported by 41% of Atripla recipients, vs. 15% of participants receiving the dolutegravir-based regimen), while the most common drug related adverse events on the dolutegravir-based regimen were in the gastrointestinal system organ class (reported by 22% of subjects receiving the dolutegravir-based regimen and 22% of subjects receiving Atripla).

"Taken together with the results of the SPRING-2 trial, the SINGLE findings suggest that, if approved by regulators, a treatment regimen containing dolutegravir may offer people living with HIV an important additional first line option in the future," said Dr. Tsutae "Den" Nagata, Chief Medical Officer, Shionogi & Co., Ltd.

"This study represents an important milestone in the development of dolutegravir-based regimens, including a single-tablet regimen, and also for the Shionogi-ViiV Healthcare joint venture. We look forward to receiving further safety and efficacy data from two Phase III studies in treatment experienced patients to continue to build a comprehensive picture of the role of dolutegravir in the treatment of HIV” said Dr. John Pottage, Chief Medical Officer, ViiV Healthcare.

Full results of this study, including key secondary endpoints, will be presented at upcoming scientific meetings.SINGLE is the second of four Phase III studies that are due to be reported in 2012. Data from the clinical trialSPRING-2 (ING113086) were announced in April 2012. Data from VIKING-3 (ING112574)and SAILING (ING111762) in treatment-experienced patients will be received later this year and will allow further characterization of the profile of dolutegravir. These studies are designed to support a future regulatory filing for dolutegravir.

About SINGLE (ING114467)

SINGLE is an ongoing phase III, randomized, multi-center, multinational, double-blind, double dummy study designed to compare the efficacy and safety of dolutegravir plus abacavir/lamivudine compared to Atripla in treatment-naive patients. The primary objective for SINGLE is to demonstrate the antiviral activity of dolutegravir plus abacavir/lamivudine once-daily therapy compared to Atripla over 48 weeks. As per study design, trial participants will continue on blinded therapy in order to assess the tolerability, long-term safety, and antiviral and immunologic activity of dolutegravir plus abacavir/lamivudine once-daily compared to Atripla over 96 weeks. Investigators will also evaluate viral resistance in patients experiencing virologic failure.

About Dolutegravir

S/GSK1349572 (dolutegravir) is an investigational integrase inhibitor (INI) currently in development by Shionogi-ViiV Healthcare LLC for the treatment of HIV. Dolutegravir does not require an additional "booster" drug be added to the regimen. Integrase inhibitors block HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T-cells). This step is essential in the HIV replication cycle and is also responsible for establishing chronic infection. Given the stage of development of this investigational HIV therapy, the full picture of the efficacy and safety of dolutegravir has not been conclusively determined.

About Shionogi-ViiV Healthcare LLC

The Shionogi-ViiV Healthcare LLC is a joint venture between Shionogi & Co., Ltd. and ViiV Healthcare Ltd., a global company with a sole focus on HIV established in 2009 by GlaxoSmithKline and Pfizer, Inc. Dolutegravir is the lead compound in the Shionogi-ViiV Healthcare LLC partnership. Shionogi-ViiV Healthcare LLC is also developing another integrase inhibitor which is at an earlier stage of development.

About Shionogi & Co., Ltd

Headquartered in Osaka, Japan, Shionogi & Co., Ltd. is a major research-driven pharmaceutical company dedicated to placing the highest value on patients. Shionogi's Research and Development currently targets three therapeutic areas: Infectious Diseases, Pain, and Metabolic Syndrome. The Company is the originator of innovative medicines which have been successfully delivered to millions of patients worldwide. In addition, Shionogi is engaged in new research areas such as allergy and cancer. Contributing to the health of patients around the world through development in these therapeutic areas is Shionogi's primary goal. For more details, pleasevisit www.shionogi.co.jp. For more information on Shionogi Inc. headquartered in Florham Park, NJ, please visit www.shionogi.com.

About ViiV Healthcare

ViiV Healthcare is a global specialist HIV company established in November 2009 by GlaxoSmithKline (LSE: GSK) and Pfizer (NYSE: PFE) dedicated to delivering advances in treatment and care for people living with HIV. The company’s aim is to take a deeper and broader interest in HIV/AIDS than any company has done before and take a new approach to deliver effective and new HIV medicines as well as support communities affected by HIV. For more information on the company, its management, portfolio, pipeline and commitment, please visit www.viivhealthcare.com.

7/13/12

Source

Shionogi-ViiV Healthcare. Shionogi-Viiv Healthcare Announces Positive Initial Data From Phase III Study of Dolutegravir-Based Regimen vs Atripla in HIV. Press release. July 11, 2012.