GSK's ViiV, under threat from Gilead-Merck collab, eyes 'ultra-long-acting' HIV drugs with Halozyme deal

GlaxoSmithKline GSK House in Brentford, UK
To develop “ultra-long-acting” subcutaneous HIV drugs, GlaxoSmithKline's ViiV Healthcare has licensed Halozyme Therapeutics' drug delivery platform for$40 million upfront. (GlaxoSmithKline)

With competition in the HIV field heating up, drugmakers are continually looking to improve treatment regimens by reducing dosing requirements. Now, GlaxoSmithKline is hoping to safeguard its lead on that front with a new partnership.

GSK’s HIV-focused ViiV Healthcare is paying Halozyme Therapeutics $40 million upfront to gain exclusive rights to the latter’s Enhanze drug delivery technology for use against four HIV targets, the two companies said Tuesday. Up to $175 million in milestones and mid-single-digit royalties on future sales are up for grabs.

The collab sees two of 2020’s Fiercest Women in Life Sciences, ViiV’s head of R&D Kimberly Smith, M.D., and Halozyme CEO Helen Torley, work together to develop “ultra-long-acting” under-the-skin medicines with dosing intervals of three months or longer for the treatment or prevention of HIV.

It builds on ViiV’s successful introduction of injectable Cabenuva as the first once-monthly complete regimen for HIV treatment in a field filled with daily drugs. The plan now is to start the first experiments with Halozyme’s platform by the end of 2021 for cabotegravir, a component used in Cabenuva, for PrEP. ViiV recently launched an FDA rolling submission for intramuscular cabotegravir as an every-other-month PrEP candidate. The company expects to wrap up the filing next month for a potential decision by the end of 2021, Smith said.

RELATED: 2020's Fiercest Women in Life SciencesKimberly Smith – ViiV HealthcareHelen Torley – Halozyme

Halozyme’s Enhanze technology uses a recombinant human hyaluronidase PH20 enzyme to temporarily break down a barrier under the skin to allow large amounts of fluid to be injected into the subcutaneous space. Therefore, drugs that are otherwise given in high doses by intravenous injections could be converted into subcutaneous injectables, offering convenience for patients.

In cabotegravir’s case, the drug is given into the muscle, which becomes a depot that slowly releases the drug over time, Smith explained in an interview. With Halozyme’s technology, the goal is to make a bigger, subcutaneous depot to host more drug in one shot.

Early studies have shown that the addition of the Halozyme enzyme doesn’t affect how cabotegravir performs, Smith said. Now, the two companies aim to be the first to find out if the pairing changes how the drug moves through the human body and to determine the upper limit of dosing and hence the longest achievable dosing interval, she said. To make the leap from once-monthly to an injection every other month, ViiV previously increased intramuscular cabotegravir’s strength from 400 mg to 600 mg per injection.

RELATED: GlaxoSmithKline's HIV PrEP challenge looms as ViiV's long-acting drug tops Gilead's Truvada in women

Halozyme’s technology has been successfully adopted in several drugs, including Johnson & Johnson’s blockbuster multiple myeloma therapy Darzalex in a subcutaneous formulation dubbed Darzalex Faspro, as well as Roche’s Phesgo, a fixed-dose combination of the Swiss pharma’s HER2 cancer meds Herceptin and Perjeta.

As Torley acknowledged, most of those applications target the convenience edge of IV-to-subQ conversion without affecting the dosing interval. The Enhanze platform did previously help Baxter—now part of Takeda—win an FDA nod for a subcutaneous version of immunoglobulin drug HyQvia with a longer-acting dosing regimen administered at one injection site. To Torley, that serves as a proof of concept for the current ViiV project.  

RELATED: Gilead, Merck join forces on long-acting HIV treatments

As a pioneer in long-acting HIV treatment, ViiV apparently doesn’t intend to rest on its laurels, not when HIV market leader Gilead Sciences is chasing it. In March, Gilead joined forces with Merck on long-acting combinations of the California company’s lenacapavir, a capsid inhibitor, and the New Jersey pharma’s islatravir, an NRTTI.

Gilead has reported encouraging data for lenacapavir as a subcutaneous drug given every six months in combo with other antiretrovirals. And Merck has been testing islatravir both as an oral and as a yearly implant.

As for Halozyme, the deal gives the drug delivery expert an opportunity to expand in small molecules, where there has been somewhat of a shift away from daily pills in favor of longer-interval treatments in certain diseases, Torley said.