According to Greek mythology, “the wound that would not heal” was inflicted by the intemperate warrior Achilles when he fell upon Telephus, son of Hercules, after invading an allied kingdom in the mistaken belief that he had landed at Troy. Terrible was Achilles’s spear, and terrible was the wound that would not heal.
Telephus recovered only after clever Odysseus intervened, persuading Achilles to use his spear to heal the wound. An oracle had declared that Telephus could only be cured by the thing that had wounded him.
If only it was that easy in modern medicine.
Nevertheless, a new San Diego startup hopes to build its own mythology—invoking Telephus as its namesake in developing a new therapy for a terrible and often intractable infection. Nowadays, the wound that does not heal is also known as the nightmare of orthopedics—a bacterial infection in an implanted prosthetic joint.
Fortunately, studies have shown the infection rate is low. Of 330,000 total hip replacements done in the United States each year, the infection rate is typically less than 2 percent. Of 670,000 total knee replacements done annually, the infection rate is about 2 to 3 percent. A variety of risk factors, such as obesity and diabetes, can worsen the odds.
But once an infection takes root in a prosthetic joint, it can be extremely difficult to eradicate. Such infections range from a chronic, low-grade local inflammation to acute, fulminant systemic sepsis. In some cases, it can lead to bone loss and loosening of the implant—and in extreme cases, amputation. The costs also are exorbitant. Total treatment costs of a septic hip implant typically run four to six times the cost of the primary procedure (which has an average cost of roughly $25,000)—with a re-infection rate that still ranges from 30 to 50 percent.
So preventing—or at least reducing—the recurrence of so-called prosthetic joint infections represents a huge unmet medical need and potentially major savings. Telephus Medical, a San Diego biotech, was founded just over a year ago to address this need. The pre-clinical startup plans to advance treatments that rely on new monoclonal antibody drugs that target Staphylococcus aureus bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), which account for 80 percent of all prosthetic joint infections.
With technology licensed from the University of Rochester lab of Edward Schwarz, who is the startup’s founder and chief scientific officer, Telephus plans to advance a monoclonal antibody to early stage trials. The company ultimately wants to develop a single-dose biologic drug that could be injected before a patient undergoes revision surgery to clean out the bacteria and repair the damage caused by a staph infection of artificial hips, knees, and other prosthetic joints.
“What we’re trying to do is supplement the patient’s immune system to fight this infection, without giving them a bunch more antibiotics, which they’re getting anyway,” says Telephus CEO Mark Benedyk, a biotech consultant and longtime industry executive.
Benedyk says he initially worked with Schwarz as a consultant, and together they developed a strategy to start a company around the original biologic product. “Eddie approached me with a good deal of very high-quality preclinical data in his animal model of implant-associated osteomyelitis,” Benedyk wrote in an e-mail, “It was immediately clear to me the high unmet medical need, and more stringent outcome requirements for reimbursement under the ACA [Affordable Care Act] made this a very valuable product.”
Telephus is now seeking to raise a $5 million Series A round to advance the company’s lead product to Phase I trials in 2016. So far, Telephus has raised more than $1.4 million from individual investors and the Wilson Sonsini law firm.
A key advantage of the germline clone that Telephus is developing, Benedyk says, is that it neutralizes a sticky enzyme that helps staph bacteria adhere to the implant surface, enabling the bacteria to form multi-layered biofilms.
Disrupting the biofilm is crucial. Otherwise, bacteria can fortify the outer layers of the biofilm, creating a kind of shield against antibiotics. The Telephus drug also is intended to supplement antibiotics generally by suppressing staph replication. That’s important because it is nearly impossible for a surgical team to cleanse all bacteria from the deep recesses within the joint, as well as from bone microfissures and patches of dead bone tissue known as sequestra, Benedyk says.
Telephus sees a growing market for its drug, as the number of joint replacement operations increase with the aging U.S. population. Infection rates are projected to increase proportionately as the 670,000 cases of knee replacement surgery now done each year grow to 3.5 million by 2030. The 330,000 annual hip replacements are expected to almost double, Benedyk says. In addition, infection rates for bone fractures that break the skin are about 25 percent, and often require a similar, all-out decontamination effort. (About 80 percent of the bacteria that cause infections reside in the first five layers of the patient’s own skin.)
In an e-mail, Benedyk writes, “The economic burden of infections is expected to exceed 50 percent of the inpatient resources available for revisions by 2025 for total hip arthroplasty [joint replacement] and by 2016 for total knee arthroplasty.”
At the same time, the American Academy of Orthopaedic Surgeons is predicting a 6,000-surgeon shortfall by 2020 in the number of orthopedic specialists needed to meet the demand for such operations. “By 2016, only 28 percent of needed knee replacements and 54 percent of needed hip replacements will be able to be completed,” Benedyk says.
If Telephus can advance its technology all the way through FDA approval, Benedyk estimates the company could generate sales of roughly $400 million in its fourth year of sales. Of course, that remains a long way off, and Telephus still faces a series of challenges that could rival the 12 labors of Hercules.