Glaxosmithkline’s majority-owned specialist HIV company, Viiv Healthcare, has been struggling to find a response to the HIV powerhouse Gilead, whose products include Biktarvy, so a positive result in the HIV prophylaxis market will come as a welcome victory.
Today Viiv said a phase II/III trial comparing monotherapy cabotegravir against Gilead's market-leading Truvada, also known as PrEP, had been stopped early after cabotegravir showed strong efficacy in preventing new HIV infections.
The 4,600-patient HPTN 083 trial in men who have sex with men and transgender women compared once-daily oral Truvada pills plus placebo injections with two monthly cabotegravir injections. Over the three years that some participants were in the study there were 12 infections in the cabotegravir group versus 38 in the Truvada group.
This represented a 0.38% incidence rate in the cabotegravir arm versus 1.21% in the Truvada arm, making a numerical 69% reduction in new infection rates.
It is interesting to note that despite the seeming strong showing cabotegravir can only claim non-inferiority to Truvada. This is because the original primary endpoint of superiority over Truvada was shifted to non-inferiority to ensure that the datasets Viiv submitted to the independent monitoring board were complete and not impacted by Covid-19.
Given that Bernstein is forecasting that pre-exposure prophylaxis could be the main engine of near-term growth in HIV, Viiv will be disappointed at being denied the chance to prove superiority at this point. Analyses of the data are ongoing.
However, on a conference call today Viiv was keen to point to the recommendation by its study's monitoring board that patients taking Truvada in the trial be offered cabotegravir.
The PrEP market has until now been dominated Truvada, but this drug is due to lose patent protection in September, opening up the window for a host of generic competitors.
Gilead had been hoping to shift patients to its second-generation drug Descovy, but given the option of lower-cost alternatives, and Descovy’s marginal safety improvements over Truvada, uptake forecasts have been modest.
Today’s data from cabotegravir could change these market dynamics. Alongside its strong showing today in preventing new infections, cabotegravir also has the advantage of being dosed once every two months.
This is an improvement on the original once-monthly dosing that has previously been tested, and could provide a valuable differentiator from generic Truvada for patients who struggle with compliance with a daily pill.
However, there are some questions as to why 12 people taking cabotegravir still managed to become infected. One theory is that individuals with lower body mass index eliminating the drug from their bodies faster. Another hypothesis is that patients in the cabotegravir arm had to take an oral dose for five weeks, and some study subjects might have failed to comply with this.
Whatever the reason Viiv will be examining the data closely, because if the explanation is to do with body mass index this could have an impact on the drug’s effectiveness in women.
Viiv is running a 3,000-patient study of women in Africa, HPTN 084, which is running 12 months behind HPTN 083. Those looking for clues around infection rates here might have to wait as Covid-19 is almost certain to impact data collection.
For now, Viiv has scored an important win in HIV prevention, and more interestingly with a monotherapy. Any longitudinal studies will be watched closely for resistance issues.