Why the first GAIN Act antibacterial drug is underwhelming

In 2012, Congress passed the GAIN Act to stimulate antibiotic drug development. Congress offered an additional 5 years of marketing exclusivity for “qualified infectious disease products” (QIDPs) (Prior TIE post). Dalbavancin is the first antibiotic approved with the new QIDP designation (FDA Law Blog). 31 more QIDP compounds are in the pipeline. Is this a sign that the 2012 GAIN Act was a success? The short answer is no.

1. Pathogens.  With all the press and political attention that antibiotics are getting recently, remember which pathogens are the most urgent (CDC Threat Report):

• Multidrug resistant Neisseria gonorrhoeae;
Clostridium difficile; and
• Carbapenem-resistant Enterobacteriaceae (CRE) and other gram-negative “ESKAPE” pathogens.

And in countries that aren’t as wealthy, add:

  • Multidrug resistant (MDR) and extensively drug resistant (XDR) tuberculosis; and
  • Artemisinin resistant malaria.

2.  Infections. We are particularly worried about blood stream and bone infections; ear aches and skin infections, not so much. From Nature Medicine:

Brad Spellberg, an infectious disease specialist at the Harbor-University of California–Los Angeles Medical Center, says that accelerated approval for antibiotics for Staphylococcus aureus skin infections, for example, is simply not necessary. “We have so many of those [antibiotics] we don’t know what to do with them all,” he says. He estimates that there are about 20 drugs available for S. aureus skin infections, yet there are few to no options for bacteremia.

3. Drug characteristics. We want a drug that is better than existing drugs in terms of safety, efficacy or administration. We prefer a drug from an entirely new class, with a new mechanism of action to delay resistance and give clinicians a powerful new choice.

How does dalbavancin stack up?

Dalbavancin is labeled to treat S. aureus ABSSSI – skin infections; in well-done pivotal trials recently published in NEJM, it was shown not to be inferior to vancomycin, a generic antibiotic that has been on the market since 1958. It is from the same class as vancomycin, with a similar mechanism of action. It targets gram positive bacteria, not the gram negative superbugs like CRE.

The main advantage of dalbavancin is that it can be dosed once per week, which will allow patients to leave the hospital much sooner. This will undoubtably save hospitals money, prevent hospital-associated infections, and be much better for patients. But it won’t do anything to solve our antibiotic crisis.

The problem lies in the design details in the GAIN Act, which weakened priority review standards to make it easier for products to obtain QIDP designations.

In other words, we set low standards and got what we asked for. But this overstates the impact of the GAIN Act. Dalbavancin was in development for over a decade; the GAIN Act is 2 years old. Dalbavancin would have come to the market with or without the GAIN Act.

Some will say the GAIN Act should be celebrated for small steps; before we build on the GAIN Act, we need to make sure those steps were in the right direction.



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