A new front has opened up in the battle between Gilead and Viiv for dominance of the HIV market: heavily treatment-experienced patients. Viiv, a subsidiary of Glaxosmithkline, struck a blow here last year with the approval of its first-in-class HIV-1 attachment inhibitor, Rukobia, but Gilead is fighting back, yesterday reporting promising data with its long-acting capsid inhibitor lenacapavir, another novel approach.
If approved, lenacapavir would have a convenience advantage, being a twice-yearly injection versus Rukobia’s twice-daily tablet. And Gilead has bigger plans for its project: the group is also studying lenacapavir in treatment-naive patients, and pivotal studies are slated to start this year in pre-exposure propyhlaxis – an area where Gilead will hope to retain its upper hand.
|Notable trials of Gilead's lenacapavir|
|Heavily treatment-experienced pts with multidrug-resistant HIV-1||Ph2/3 Capella, NCT04150068||Positive data reported, filing due H2 2021|
|Treatment-naive HIV pts||Ph2 Calibrate, NCT04143594||Data due H2 2021|
|PrEP in high-risk men/transgender women/nonbinary people||Ph3||Due to start H1 2021|
|PrEP in young women||Ph3||Due to start H2 2021|
|Source: clinicaltrials.gov & Gilead Q4 2020 earnings call.|
For now, though, the focus for lenacapavir is heavily treatment-experienced patients with multidrug-resistant HIV who were failing on antiretroviral drugs, the setting for the phase II/III Capella study. Results from the trial were reported yesterday at the Conference on Retroviruses and Opportunistic Infections (CROI).
Patients in the study were given oral lenacapavir or placebo, plus their failing antiretroviral regimen, for a 14-day lead-in period, then received a subcutaneous injection of lenacapavir on top of optimised background therapy. There was also a non-randomised cohort of patients who all received lenacapavir from the start.
Of the 26 patients with 26 weeks of follow-up from the subcutaneous lenacapavir dose, 73% had an undetectable viral load, defined as less than 50 copies/ml. Gilead had already disclosed that the randomised portion of Capella had met its primary endpoint.
The latest results look favourable to data seen with Rukobia, although the usual caution about cross-trial comparisons is compounded here by the small patient numbers in Gilead’s study. In the Brighte trial of Rukobia, also in a heavily pretreated population, the rate of virologic response was 53% at 24 weeks, although this was seen across 272 patients. Rukobia was approved in the US last July for heavily treatment-experienced patients, who Viiv estimates account for around 6% of all HIV patients on therapy.
PrEPping for bigger things
With these small numbers, it is no wonder that Gilead is setting its sights on a bigger slice of the market. The real prize would be pre-exposure prophylaxis (PrEP), where Gilead’s oral drug Truvada has dominated; however, that product lost patent protection in September, and the group has been trying to switch patients to its follow-on Descovy.
In the PrEP space Viiv got a boost last year from positive data with its own long-acting HIV therapy cabotegravir: a win against Truvada in the HPTN 083 trial in men who have sex with men was followed by success in the HPTN 084 study in women. In both trials, cabotegravir was injected every two months.
Gilead will no doubt hope that the greater convenience of an injection every six months will help it keep the upper hand in PrEP, assuming that lenacapavir’s trials here read out positive. The latest data increase the likelihood of a win in PrEP, Leerink analysts believe.
If the results bode well for bigger markets they might also lead to upgrades: sellside consensus puts lenacapavir’s 2026 revenues at $787m in 2026, according to Evaluate Pharma.