Do Clinicians Have an Obligation to Support the Struggling Antibiotic Market?: Public Health Watch

With investments in novel drugs on the decline, the decision on whether or not to use a new product may serve to foster or stunt development.

Christopher Ohl, MD, believes strongly in incorporating new antimicrobials into clinical practice once they become available—provided they make sense for patients based on available clinical data.

Recent events in the pharmaceutical industry, particularly within the antibiotic pipeline, have brought renewed focus on such decisions. As chronicled by Contagion® Editor-in-Chief Jason C. Gallagher, PharmD, FCCP, FIDP, FIDSA, BCPS, Achaogen, manufacturer of the novel aminoglycoside plazomicin, was forced to declare bankruptcy due in part to sluggish sales (it didn’t help that the drug failed to receive US Food and Drug Administration [FDA] approval to treat bloodstream infections).

The news begs the question: Are infectious disease physicians and pharmacists effectively discouraging innovation in the antimicrobial space by being slow to bring new drugs into clinical practice? According to Ohl, his medical center was among the first to bring plazomicin on formulary for its FDA-approved indication: complicated urinary tract infections.

“We are disappointed to not see that drug do well, but it’s a complicated issue,” the professor in the section on Infectious Diseases at Wake Forest University School of Medicine told Contagion®. “I’ve been around long enough to remember the so-called ‘fluoroquinolone wars,’ when multiple companies were bringing new fluoroquinolones to market and battling it out for market-share. But the world’s changed a lot in the last 20 or 30 years. It used to be that when new drugs were introduced to the infectious disease market, there was real heavy investment pre- and post-launch. Unfortunately, the tools we need now are harder and more expensive to make.”

At issue here, of course, is the fact that pharmaceutical companies operate in a for-profit environment, and with development costs (including clinical trials) for antibiotics—or any drug really—typically exceeding $1 billion, manufacturers need to be sure they can turn a profit with any new launch. Unfortunately, there’s a bit of a catch-22: Those in charge of hospital formularies need to be able to justify the cost of prescribing a novel drug—based on its clinical benefits over existing options and, frankly, its price compared with those alternatives.

“Everyone understands there’s an expense associated with developing new antibiotics,” noted David W. Kubiak, PharmD, an advanced practice pharmacy specialist at Brigham and Women’s Hospital. “But hospitals have a very narrow margin, so any new drug has to fill an unmet need.”

And, although drug companies may want to sell more pills, to cover and make a profit over research and development expenses, infectious disease specialists are loath to use more—at least in the case of antibiotics—because of the threat of resistance. So, what to do?

Ohl suggested that pharmaceutical companies need to “be patient and be in [the antibiotic space] for the long haul.” This, he said, means understanding that they won’t have a $4 billion launch” with an antibiotic, but that “a sound pricing strategy” to start, one that can allow for increases as use of the drug evolves from “directed therapy to empiric therapy”—based on emerging data—can be a win-win for companies and clinicians alike.

According to Kubiak, Merck effectively took this approach with daptomycin (Cubicin) and found success. More recently, Tetraphase Pharmaceuticals, which has seen share prices for its stock drop to roughly 70 cents in recent years over investor fears regarding the future of the antibiotic market, appears to be following that example with eravacycline (Xerava), a tetracycline that recently received FDA approval for complicated intra-abdominal infections (cIAI). The company has announced its intention to keep prices for the drug relatively low ($175 per treatment day) to “support [its] strategy of having [the drug] used for the empiric treatment of cIAI.”

However, more than a little corporate creativity is clearly needed. Gallagher noted that the time to reconsider reimbursement models for antibiotics is long overdue, given that we are well into the age of resistance. “Hospitals shouldn’t be penalized for using an antibiotic that costs $1000 per day versus one that costs $5 per day if it’s the best option available,” he explained.

And, both Ohl and Kubiak advocated for a system set up based on enhanced surveillance of resistant bugs (that includes data on patient type and strain phenotype) that would enable hospitals to make bulk purchases of antibiotics as needed, perhaps with government assistance, should resistant strains arise on-site. Speaking of government, given that the US Centers for Disease Control and Prevention has made the issue of antibiotic resistance a priority, perhaps other agencies can follow suit with aggressive programs designed to foster development, distribution, and use of novel drugs that can effectively treat resistant strains. According to Ohl, this may entail the FDA allowing pharmaceutical companies to extend patients on more profitable drugs in exchange for sticking with a lower-margin antibiotic for the “public good.”

Furthermore, a commentary published in The New England Journal of Medicine advocates for a “non-profit” drug development model, similar to that established by the TB Alliance for novel therapeutics targeting resistant bacteria. Such initiatives, the authors write, could work in partnership with for-profit manufacturers.

Either way, although “we really are in trouble when it comes to antibiotic development,” as Gallagher puts it, clinicians should consider the overall business climate but remain careful when it comes to using novel drugs.

“I don’t think the answer is simply to drive up demand,” Ohl said. “That’s just going to make these drugs have a short half-life in the market, as we saw with MRSA and VRE, where some drugs were overused in some places and it didn’t take long for resistance to develop. That’s not going to help anybody, the drug companies, the hospitals, or patients.”