It wasn’t easy navigating the manufacturing and controls issues that had led the FDA to reject ViiV Healthcare’s first pitch for the once-monthly HIV regimen cabotegravir and rilpivirine. But even as Kimberly Smith was knee-deep in sorting out those problems and putting together a new package that finally won the regulators over this January, her business development team kept looking for things that would take them to the next level.
Cabenuva, the FDA-approved therapy, could keep the virus at bay for a month at a time. Studies suggest — and they have an EU OK to back it up — they could extend the dosing interval to as long as two months, a big leap from daily pills.
Still, they wanted to see if they can push even further: Can you go out to dosing every three months? Four months? Or even six months, the Holy Grail in their minds? And to do so, they needed help.
“The difference [between] the one-month dosing and the two-month dosing is a bigger dose,” Smith, the head of R&D at ViiV and a longtime HIV researcher, told Endpoints News. “But we’re maxed out.”
That hunt for something “outside of the box” led ViiV to Halozyme a little over a year ago, enticed by a drug delivery technology that promises to dramatically increase the maximum dose, thereby extending dosing intervals.
A few preclinical studies with cabotegravir later, the GlaxoSmithKline subsidiary is ready to bite.
ViiV is dropping $40 million upfront to exclusively license Halozyme’s ENHANZE platform as it applies to four HIV targets — corresponding to four small and large molecule candidates in its own pipeline. Each target is tied with $175 million in future development and commercial milestones, adding up to $700 million total.
“We do find that doing a little bit of work beforehand sometimes does help just to expand the thinking as to where we might go with the collaboration,” said Halozyme CEO Helen Torley.
Currently, Smith explained, cabotegravir is given intramuscularly together with J&J-partnered rilpivirine. In the muscle, the maximum volume one can inject is 3ml — the dose ViiV needs to reach two-month dosing.
For subcutaneous injections, which is Halozyme’s specialty, the conventional limit is 2ml. But the biotech has figured out a way to deploy the recombinant human hyaluronidase PH20 enzyme (rHuPH20) to temporarily degrade hyaluronan under the skin, breaking down a key barrier to the flow of fluid. During that window, you can deliver as much as 20ml of drug. It’s a possibility that’s drawn multiple big players, like Roche, Bristol Myers Squibb and IQVIA, to a series of deals (even if it hasn’t helped Halozyme develop a viable drug of its own).
“And so it gives you a lot more room to increase your dose,” Smith said, with the hope that it will give her discovery team even more flexibility when combined with drugs that were already selected for their long-acting potential.
The longer you can extend the dosing interval, after all, the better. And ViiV is not alone in that conclusion: HIV giant Gilead is in hot pursuit of the same goal, and recently teamed up with Merck in an unusual alliance to create a potential new franchise.
But Smith reckons they are at least five years ahead, with hard-earned experience and trade secrets that can only be gleaned when you’ve actually been down in the trenches. Like getting a CRL.
“When someone starts down this path, trying to create a long acting regimen, they don’t know the things that we know because we’ve been there,” she said. “We’ve been doing this for years now. So we’re taking all those lessons and building up to get to the next level.”