GSK’s ViiV Healthcare and its bimonthly pre-exposure prophylaxis (PrEP) medicine Apretude had to make room for another long-acting PrEP option this summer, when rival Gilead Sciences rolled out Yeztugo to much fanfare.
But despite Yeztugo’s twice-yearly convenience factor, unprecedented efficacy performance in trials and award-winning pedigree, GSK has long maintained that one aspect of the rival drug’s clinical profile would block it from snatching the entire long-acting PrEP market.
Now, armed with a new open-label crossover study, the company can back up its theory that the injection-site reactions from Gilead’s drug may give some potential users pause.
GSK’s CLARITY study, presented at the 20th European AIDS Conference (EACS) in Paris, examined the tolerability and acceptability of Apretude and Yeztugo to determine which drug would be preferred by the 63 HIV-negative adults who participated.
In the study, participants were randomized to receive either Apretude or Yeztugo at day 1, followed by the other drug at day 15. Apretude is administered as a single intramuscular injection, while Yeztugo is given via two subcutaneous injections. Injection site reactions were a focal point of the study, with the primary endpoint being local reaction acceptability at seven days after each injection.
Ultimately, 69% of the participants listed Apretude injections as “totally or very acceptable,” while 48% said the same about Yeztugo after a single dose of each drug. Nine out of ten of the participants determined that they preferred Apretude to Yeztugo, according to GSK's release.
"Understanding potential differences in acceptability and tolerability of options is an important consideration when choosing between long acting injectables,” ViiV’s Chief Medical Officer, Jean van Wyk, noted in a GSK press release. “These early findings provide valuable insights into long-acting injectable options to help empower individuals and their healthcare providers to make fully informed choices.”
The majority of those who favored Apretude cited less pain during injection administration, less post-injection soreness and factors surrounding the size of injection nodules or swelling, according to GSK.
Still, some study participants did prefer Yeztugo to Apretude. Those who preferred Yeztugo listed similar rationale, namely less pain and soreness after injection.
Other than PrEP user preference, GSK took note of the occurrences of injection site reactions (ISRs) between the two drugs. The company found that 4.4 times more ISR events were observed after Yeztugo than Apretude in the study, and that Yeztugo was associated with a “significantly higher risk” of visible or “palpable” ISRs.
The most commonly reported reaction was pain, but those stats came out evenly, with 82% of participants citing pain at their Yeztugo injection site and 80% after Apretude.
GSK has previously pointed out that the injection-site nodules reported in Gilead’s phase 3 Purpose 2 Yeztugo study could be “potentially an issue” for PrEP users who are “body-image conscious,” as the company's president of corporate development, David Redfern, put in a February investor call.
Gilead, meanwhile, countered that “injection site reactions were relatively common and expected, and discontinuations were rare” across its two phase 3 trials, a spokesperson said at the time, adding that nodules were “usually not visible.”
Yeztugo is still in the early days of its global rollout, but Mizuho analysts previously forecast swift uptake and $8 billion in peak sales. GSK garnered 279 million pounds sterling ($381 million) in Apretude sales last year.