A few hours ago, Allergan plc (NYSE:AGN) hit markets with the latest results from a phase 3 study of AVYCAZ – it’s antibiotic treatment targeting complicated urinary tract infections (cUTI). The FDA approved the treatment way back in February this year, but – due to a lack of safety and efficacy data – only approved it for patients that have not responded to all other treatment alternatives. This limiting factor reduced the potential patient pool considerably, and in an attempt to widen the indication, Allergan teamed up with AstraZeneca PLC (NYSE:AZN) to conduct further trials. These trials – RECAPTURE 1 and RECAPTURE 2 – focused solely on safety and efficacy, and from both the perspective of the FDA and the EMA were considered as one individual trial. The goal now is for a supplemental new drug application (sNDA) to head towards both regulatory authorities, and get the indication widened. So, what’s next?
First, let’s have a quick look at the drug itself. The drug is a combination of two elements – ceftazidime and avibactam. The former is a widely used and already well-established antibiotic used to target gram-negative bacteria. These types of bacteria cause some of the most serious infections – primarily as a result of their impenetrable cell wall making them hard to treat and prone to antibiotic resistance. They produce what’s called lactamase, which is an enzyme that breaks down antibiotic treatments. This breaking down is at the core of antibiotic resistance, and at the root of AVYCAZ’s efficacy. Avibactam is a lactamase inhibitor, meaning it protects the ceftazidime antibiotic from the lactamase. In doing so, it makes the bacteria no longer resistant to the ceftazidime antibiotic – ergo sum, increased efficacy. The treatment acheived accelerated review, but as part of this acceleration and approval there was not enough safety and tolerability data available to approve it across a wide indication. Alongside the FDA approval announcement, we got this statement:
“It is important that the use of AVYCAZ be reserved to situations when there are limited or no alternative antibacterial drugs for treating a patient’s infection.”
With the announcing of the RECAPTURE trial results, it looks as though this limited indication is about to expand. The trial compared AVYCAZ to a placebo arm across than 1000 hospitalized cUTI patients in 30 countries. The FDA and the EMA had two separate definitions of success across the trial, but both definitions were met and proven as being statistically significant.
David Nicholson, Executive Vice President & President, Global Brands R&D at Allergan, had this to say alongside the announcement:
“We are very pleased by these results, which we plan to submit to the FDA to further support the use of AVYCAZ as a treatment option for patients with these serious and life-threatening complicated urinary tract infections.”
So what’s next? Well, now comes the sNDA. The FDA will accept the supplementary documents and take into consideration the updated results when considering an expansion of the treatment’s potential indications. The key thing here is that safety and tolerability were what both arms of the trial focused on, and with these met, it is difficult to see why the FDA wouldn’t expand the treatment’s indication. Especially when the lack of data to support these two elements of the approval were what restricted it in the first place. It goes without saying that nothing is guaranteed, but markets will likely price in this extended approval going forward in advance of its announcement.
Despite the positive release, Allergen is trading slightly down for the day, while Astrazeneca is up 2.5% at time of writing.