A technician holds an agar plate containing bacteria cell culture at a Bugworks Research India Ltd. laboratory in Bengaluru, India, on Thursday, May 31, 2018. The rapid spread of resistant bacteria has made India the epicenter of a war to prevent a post-antibiotic world, where people would once again die in their thousands of commonplace infections. Faced with this, the Indian government has begun to act, providing early research funding to startups like Bugworks and providing advice and support. Photographer: Samyukta Lakshmi/Bloomberg via Getty Images (Photo: Samyukta Lakshmi/Bloomberg/Getty Images)

Four years ago, antibiotics developer Tetraphase Pharmaceuticals Inc. had a market value of almost $2 billion. Now its shares trade for about 70 cents as investors flee the market for new drugs that kill bacterial infections.

To survive, the company said last week it would cut research, reduce staff and try to divest three drugs it has in development. It plans to focus all of its efforts on marketing Xerava, a recently approved hospital drug that fights particularly tough abdominal infections.

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Even as deadly strains of bacteria proliferate around the world, big drugmakers are getting out of the antibiotics market, leaving many new products in the hands of tiny startups. But most new antibiotics for dangerous strains are selling poorly because doctors hold them in reserve until they’re absolutely necessary, concerned about creating drug resistance. And price-sensitive hospitals have been slow to switch to the drugs from cheaper generics.

“In my 20 years, I have never seen it any worse than this,” said Tetraphase Chief Operating Officer Larry Edwards, who is being promoted to chief executive officer as part of the Watertown, Massachusetts-based company’s restructuring. “Investors have shied away.”

Always Challenging

Edwards, a veteran antibiotics marketer, said it had become apparent that Tetraphase simply didn’t have the money to continue testing its other drugs while investing in the launch of Xerava. The reorganization and other cost-saving efforts will save about $8.2 million annually, the drugmaker said last week.

“It has always been a challenging industry to be in,” he said. But now, “everybody wants an immediate return.”

Unlike many new expensive cancer drugs, which can generate big sales quickly, it takes time to get antibiotics on a hospital’s covered-drug list and to get doctors comfortable with prescribing them, Edwards said. Sometimes the process can take years.

Crashed Model

Another small firm specializing in antibiotics, Achaogen Inc., filed for bankruptcy protection in April, less than a year after getting approval for a drug for urinary tract infections that killed resistant strains in the test tube. In June, the company, which once had a market value of about $1 billion, reached an agreement to sell most of its assets, including the drug Zemdri, for just $16 million as part of a bankruptcy auction.

“The business model, the way we reimburse and pay for antibiotics, has just fundamentally crashed,” said Kevin Outterson, a Boston University law professor who has studied market failures in the antibiotics area. The government needs to act in three to six months to improve the reimbursement for hospital antibiotics or the U.S. may lose even more capacity to develop new bacteria-fighting drugs, he said.

A bill introduced in the Senate this month would allow the government’s Medicare program for seniors to offer additional reimbursements to hospitals that use certain antibiotics to treat a serious or life-threatening infection. The measure is backed by the Infectious Diseases Society of America, which calls it “urgently needed.”

A number of antibiotics companies have less than a year of cash left, said Alan Carr, an analyst at Needham & Co. Skittish investors are unfairly lumping all antibiotics makers together, regardless of the quality of the drug or potential size of the market, which differ from company to company, he said.

Unless something changes, “it is entirely possible we may see more bankruptcies,” he said.

Some small antibiotics makers misjudged the market by developing high-priced drugs narrowly focused on rare, resistant strains that make headlines, not drugs for the partly resistant strains that intensive-care doctors see on a regular basis, said Andrew Shorr, a pulmonary critical-care physician at MedStar Washington Hospital Center.

“There is a misalignment between what the physician sees as his or her unmet need and what is being developed,” said Shorr, who has consulted for Tetraphase, Achaogen and others. Because doctors often don’t know which strains a patient has when they begin treatment, they’re unlikely to turn first to an expensive new drug.

Edwards said Tetraphase has avoided some of the pitfalls that hit other companies. It built a targeted sales force for Xerava with representatives experienced in selling to hospitals. It priced its drug at $49 a vial, or less than $200 a day for most patients, making it more affordable. Xerava had sales of $341,000 in the first quarter, which are on track to double in the next three-month period, he said.

Still, Edwards admits, “There is some race-against-time element to it.”

Steve Brozak of WBB Securities predicts many more restructurings among antibiotics makers.

“Tetraphase is doing what they have to do to survive,” he said. “They are trying to show positive traction by cutting their expenses, streamlining the operation and focusing on one thing: sales.”

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