8. Dolutegravir

Dovato
GSK's bellwether HIV drug dolutegravir is slated to lose its exclusivity in 2028. (GSK)

Dolutegravir
Company: GlaxoSmithKline
2020 sales: $6 billion
Key patent expirations: 2027 to 2029

GlaxoSmithKline’s dolutegravir has been a staple of its portfolio of HIV drugs under joint venture ViiV Healthcare. But with a key patent loss coming in 2028, the company is now placing its bets on long-lasting injections versus daily pills. 

Dolutegravir is the molecule found in four of GSK’s best-selling HIV brands—Tivicay, Triumeq, Juluca and Dovato. All said, dolutegravir-containing products reaped £4.70 million (roughly $6 million) in 2020, accounting for just over a quarter of GSK's total pharma sales. 

Those drugs are set to have to bear generic pressure after dolutegravir's patent expires in 2027, Moody's says. There are two patents protecting dolutegravir, one for its molecule that expires in 2027 and another for a crystal form that runs out in 2029.

In 2017, the crystal patent faced challenges from generic giants such as Mylan, Cipla, Sandoz and Dr. Reddy's, with the companies claiming the patent was invalid and their products did not infringe on it, according to GSK's annual report

GSK has since reached deals with Mylan, now under Viatris, and Laurus, a successor to Dr. Reddy's, the filing said. Meanwhile, the company has launched a patent infringement suit against the other defendants, which include Cipla, Apotex, Lupin and Sandoz. A trial date hasn't been set. 

In the meantime, a weathered GSK, facing fierce investor pushback amid its decision to split into two companies by 2022, is now eyeing the more convenient long-acting injectables over daily pills to fill the void. 

RELATED: GSK's long-acting HIV injectable, Cabenuva, finally snags its FDA green light

By 2031, ViiV expects 90% of its HIV business to come from long-acting regimens, CEO Deborah Waterhouse said on a June call with investors. 

After a setback in 2019, the company eventually scored an FDA nod for its once-monthly injectable HIV treatment, Cabenuva, for patients who are already virologically suppressed. Cabenuva combines ViiV’s cabotegravir and Johnson & Johnson’s rilpivirine.

Cabenuva became the world’s first complete long-acting, injectable HIV treatment. ViiV is aiming to win an FDA nod for the even lower every-two-month dosing frequency as well, which it already achieved in Europe and is anticipating will come in the U.S. by year’s end. 

On top of that, the drugmaker launched a rolling submission with the FDA for cabotegravir in pre-exposure prophylaxis (PrEP) and hopes to win a go-ahead by late 2021, ViiV said. 

ViiV recently partnered with San Diego, California-based biotech Halozyme to try to push its dosing interval out even further, potentially from every two months to three to six months. 

“This significantly reduces our exposure to genericization and supports profitable revenue renewal in our HIV portfolio,” GSK CEO Emma Walmsley said on the June call. 

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

The company is facing competition from two heavyweights: Gilead and Merck & Co. The drugmakers announced plans in March to combine their antiviral drugs—Gilead’s lenacapavir and Merck’s islatravir—to develop a once-weekly oral and an injectable for once every three months. Not to mention some generic makers have already tried to challenge 

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.

But GSK doesn't seem to be worried. Executives reiterated that the U.K.-based pharma already has a five-year head start over its competitors in HIV treatment and if all goes well with the FDA, in PrEP since its competitors don’t expect to immediately hit the market. 

“Patients tell us over and over, the longer, the better,”  ViiV’s head of R&D, Kimberly Smith, M.D., said on the call when asked about the Gilead and Merck duo. “So we're not the least bit intimidated by the idea of oral versus injectable.”

8. Dolutegravir