The Bacterial Antibiotics Pipeline: Still Broken, No Fix in Sight

I’ve been heads down working on the new startup recently, but had to pause at the news that J&J is exiting the bacterial antibiotics space. They’ll still develop antivirals (targeting HIV, flu, and the common cold) and vaccines (including one against ExPEC, extraintestinal pathogenic E. coli), but it looks like they’re winding down efforts against all bacterial targets. And so they join the long list of pharma companies who have abandoned antibiotics: AstraZeneca, Boehringer Inghelheim, Bristol Myers Squibb, Merck, Sanofi… It might actually be easier to list the companies who are still in the fight:

  • GSK, developing gepotidacin for urinary tract infections (UTI) and gonorrhoea, a variant of tebipenem for UTI, and a few compounds targeting tuberculosis (GSK3036656, BVL-GSK098, GV118819, GSK2556286), and one more for UTI (GSK3882347)
  • Otsuka, focusing purely on tuberculosis and multidrug-resistant (MDR) tuberculosis with delamanid and quabodepistat
  • Genentech/Roche, with RG6319 for UTI and RG6006 for A. baumannii infections
  • Pfizer, which gets points for legacy, but not for innovation. Their pipeline lists two antibiotics in development, ceftazidine-avibactam for complicated UTI and aztreonam-avibactam for infections caused by gram-negative bacteria generally, both of which are combinations of already-approved antibiotics.
  • Shionogi, which is pursuing additional indications and uses for cefiderocol (trade name Fetroja, approved in 2019 and one of the most recently-approved antibiotics)
Merck’s pipeline webpage, which still lists antibiotics as a therapeutic area but lists no assets.

This is down from nine companies last year (per this Milken Institute report, page 4). To make matters worse, this is a delayed snapshot: the assets listed above are mostly in phase II or III clinical trials, meaning they’re the result of ~10 years of R&D work. Pharma companies rarely list the assets that haven’t yet entered clinical trials, so we don’t always know what/how many pre-clinical assets a company working on unless someone out of their way to mention them. The number of pre-clinical assets matters because only a fraction of these will successfully make it into clinical trials, let alone approval by the FDA.

The J&J layoff gives us a glimpse into what their bacterial antibiotic pipeline looked like including pre-clinical assets, and it was thin. Three assets (interestingly, two of them bacteriophage-related). In contrast, J&J likely has >100 (and perhaps hundreds) of pre-clinical assets in oncology.

A screenshot of the J&J infectious disease pipeline from the layoff announcement (Source: Fierce Pharma’s press release).

And for most of the other companies listed above listed above? I’m guessing each has at most five pre-clinical antibiotic assets, and in a few cases that number is probably zero.

While I’m sure J&J will draw ire for this exit, I can’t blame them for getting out. Many words have already been written about how broken the market is for bacterial antibiotics (if you need a primer, here’s a Nature article or just follow John Rex at AMR Solutions). In the past decade, antibiotics-focused companies like Achaogen and Melinta just plain went bankrupt after successfully getting new antibiotics to market. Nabriva is shutting down as of January this year. Tetraphase was bought out by La Jolla Pharmaceuticals in 2020, while Entasis got bought out by asset management company Innoviva last year. Summit Therapeutics and countless others have pivoted to other disease areas (usually oncology). And arguably the company with the biggest commercial success in antibiotics of the last few years, Insmed, insist that they’re a rare disease company and have structured their pipeline accordingly.

As a society, we’ve given companies the mandate that they must try to make a profit for their shareholders, and within the bounds of legality and regulation, maximize that profit to shareholders. Given the track record above, how can we possibly expect pharma to stay in antibiotics development?

In the meantime, we’re still losing more than 1 million lives a year to antibiotic resistance. Stay safe out there, because the antibiotics might not help you.

* Note: it’s been several months since I’ve worked in the antibiotics space and I’m far from the most experienced person in it. If you note any errors above, feel free to ping me.

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