Introducing Dolutegravir

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Treatment Horizons by Chael Needle

Surpassing Expectations
ViiV Healthcare introduces its first FDA-approved agent

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ViiV Healthcare is exclusively devoted to the treatment of HIV disease, and the singular focus is arguably paying off. Tivicay (dolutegravir) is the first drug out of the ViiV Healthcare pipeline to be FDA-approved. The integrase strand transfer inhibitor is indicated for use in combination with other antiretrovirals in the treatment of HIV-1 in adults and children ages twelve years and older weighing at least 40 kg (approx. 88 lbs), and it boasts a checklist of positive attributes.

Adherence-friendly once-daily dosing (50 mg) with a single tablet, check. Can be taken with or without food, any time of the day, check. No boosting required, check. Favorable side effect and drug interaction profile, check. High barrier to drug resistance, check.

In addition, Tivicay has been shown to be effective for those with resistance to two or more classes of antiretrovirals, as well as those who have developed resistance to raltegravir and elvitegravir. It has been shown to be superior to raltegravir in integrase-naive, treatment-experienced patients; it’s been shown to be non-inferior to raltegravir in treatment-naive patients, as well. It also compares favorably with efavirenz when used in a first-line therapy. Studies have also shown dolutegravir, in combination with abacavir/lamivudine, to be superior to tenofovir/emtricitabine/ efavirenz (Atripla). A study comparing dolutegravir with darunavir is in the works.

If it sounds like ViiV Healthcare has done its homework before bringing the agent to pharmacy shelves, it has. In its submission to the FDA, ViiV presented data from four pivotal Phase III clinical trials, cumulatively treating 2,557 adults (who received at least one dose of study medication). And that broad-based approach to patient needs is not a fluke, but part of the DNA of the ViiV pipeline.

Or, as John Pottage, MD, Chief Scientific and Medical Officer, ViiV Healthcare, puts it, ViiV’s “secret sauce”—namely, a “focus on and commitment to all HIV patients. We’re focused on everybody.” And everything HIV. It’s not concerned with a niche, in other words, but the whole of the HIV landscape.

ViiV knows that the bar is set high, but, not content to rest on the past successes of its heritage pipelines, it dismisses the idea that ‘HIV therapy is good enough. We don’t need anything more.’ Dr. Pottage has heard this espoused in some corners of the HIV research community. “We don’t agree with that,” he says.

As a company formed out of a partnership between GlaxoSmithKline and Pfizer nearly four years ago, with Shionogi as a recent addition, ViiV has proceeded from the start to develop a pipeline that ongoingly takes into account the current standards of care and their benefits and limitations. For example, when ViiV developed Tivicay, explains Dr. Pottage, “we wanted to look at the barrier to resistance, safety, potency, drug interactions, which is a problem with some medicines, and also fixed-dose combinations/single-tablet regimens, which we are [intensely] committed to. So we put all of those things into the mix.”

“As dolutegravir was being developed we had initial findings that looked pretty good,” says Dr. Pottage. But ViiV didn’t settle for a limited label based on “pretty good” initial findings, a label which most likely could have been obtained. It pursued not only a wide range of patients—particularly treatment-naive patients, integrase-naive patients, patients with integrase resistance, among others—but also an early pediatric program. “We also did more than thirty drug interactions studies,” he continues. From the start, they asked: What would a prescribing physician want to know? What would a patient want to know?

The result is a “thick” label—much and varied data now rather than later. “We really put dolutegravir through its paces, so to speak. By doing that, I do think we came out with great results, a great package, which is the most important [result]. So when someone wants to prescribe the drug, they know all the different situations of where it fits in…,” he notes, affirming the importance of individualized therapy and any agent’s high adaptability to regimens.

Most importantly, “what patients need are options,” says Dr. Pottage. “Even though people may succeed with the medicines we have now, and do go a long time with them, we need to keep turning out new options and keep trying to improve on that. We’re not interested in just putting out another Atripla, or another me-too drug. Atripla is a great drug! We don’t need to make a new one of that….We need some advances on that.” In this case, researchers considered Atripla’s tolerability problems and aimed to improve upon them while maintaining similar if not superior efficacy. “So our research aims to take the good things of existing therapies and then fix those things or show where improvements can be made.”

ViiV is strongly committed to conducting additional studies on Tivicay. A Phase III study is currently underway to evaluate the safety of the drug in children under 12. And ViiV is seeking to submit regulatory filings on a single-pill, fixed dose combination containing dolutegravir, abacavir, and lamivudine in the U.S. and Europe by the end of 2013. Other single-tablet regimens are in early development as is a relative of dolutegravir called 744, an injectable integrase inhibitor in a long-acting formulation. “You would just come into the office or some location and you would get a shot, and then you wouldn’t have to come back for another one to three months,” says Dr. Pottage, elaborating on the vision for the ongoing research. It might be beneficial for those struggling with adherence, he adds. Like Tivicay, it sounds like another opportunity to consider: ViiV la différence.

Chael Needle wrote about immunotherapy candidate AGS-004 in the August issue.