FDA decision on long-acting cabotegravir/rilpivirine (Cabenuva, Vocabria) injections delayed due to scale-up manufacturing problems

On 21 December 2019, ViiV Healthcare issued a press release on the recent FDA decision not to approve cabotegravir/rilpivirine (CAB/RPV LA) long-acting injections. [1]

This was unexpected, given that CAB/RPV LA had successfully completed phase 3 studies (ATLAS and FLAIR), showing high efficacy and low side effects. CAB/RPV was non-inferior to standard of care combinations in treatment-naive and switch studies and reported improved quality of life compared to oral combinations in study participants.

Instead, the FDA has issued a complete response letter relating to chemistry and manufacturing controls (CMC), but the press statement stresses that there are no new safety concerns for these compounds.

The letter itself has not been published and specific details about these concerns were not included.

Cabotegravir is an integrase inhibitor developed by ViiV Healthcare and rilpivirine is an NNRTI developed by Janssen Sciences. Development of CAB/RPV long-acting combination is led by ViiV, with the trade name Cabenuva in the US and Vocabria in the EU.

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At a more recent community meeting, the company were more specific that the manufacturing problem was related to scale-up. [2]

This has been a problem with some earlier HIV meds as large scale production for a marketed drug is very different to smaller productions to just cover research studies.

ViiV are clear that the company are working with the FDA to resolve these issues. Phase 3 results meant that approval was expected, so this will hopefully be a short delay that can be resolved.

There has always been high interest in options for HIV treatment other than oral medicines and this announcement is likely to just extend the time a little longer before these become available.

However, certainly for people in the UK, access will depend on many factors, including cost.

There are many potential benefits from injectable ART, at least for people who have difficulty with pills, and this will also provide new options for how HIV treatment is delivered.