If You Think Approval Is Hard, Try Selling A New Antibiotic

Getting approval of a new antibiotic is just the first hurdle. Launching an anti-infective in the hospital setting is particularly challenging for sponsors pressured by both the requirements of antibiotic stewardship and an especially challenging reimbursement climate, as Theravance learned with Vibativ.

Theravance Biopharma Inc.'s Vibativ (telavancin) illustrates the labor-intensive "high science/high medicine" promotional efforts needed to launch an anti-infective in the hospital setting.

Theravance had been hoping for $20m in 2015 sales for Vibativ, an injectable lipoglycopeptide antibiotic that it re-launched in 2013. But the company lowered its guidance to between $9m and $12m as the demands of the market became apparent, Theravance Senior VP-Operations Frank Pasqualone said in an interview.

"We probably overestimated our ability to generate sales very quickly vis a vis the process that goes on in the hospital," he said. "Remember, we are a new commercial organization."

Theravance did not originally intend to be the primary marketer for Vibativ. The drug was first approved, for complicated skin and skin structure infections, in 2009 in partnership with Astellas Pharma Inc. But Astellas walked away as manufacturing issues caused Vibativ to be withdrawn from the market in 2012. Theravance brought it back with the addition of a hospital-acquired and ventilator-associated bacterial pneumonia claim in late 2013. but said at that time that it was seeking another firm's assistance for commercialization (Also see "Theravance Re-Introduces Vibativ In The U.S. Independently (For Now)" - Pink Sheet, 14 Aug, 2013.).

The late-stage antibiotic pipeline is largely dominated by emerging companies like Theravance (see related story, (Also see "Anti-Infective R&D Ecosystem Getting Healthier, But Trials Remain" - Pink Sheet, 16 Nov, 2015.)). Barring a sudden flurry of deal-making, these other sponsors of new antibiotics are likely to find themselves along a similar learning curve.

Formulary Coverage Is Just The Start

Formulary coverage has been "one of the success stories" in the Vibativ launch, Pasqualone said. "We're almost double what we were through the entire 2014 timeframe."

But, Theravance learned, "just because it goes on formulary does not mean immediate uptake."

Theravance is positioning Vibativ as an agent to be used after vancomycin for "tough cases." Vancomycin has a long history of use and is available generically. Efforts to reduce hospital-acquired infections have put the economic responsibility for nosocomial infections on the hospital itself, making hospital pharmacy and therapeutics (P&T) committees especially cost-conscious.

"If the customer … even gets a hint that you are suggesting to replace all their vancomycin, they just turn off," Pasqualone said.

Instead, "we try to have a dialogue with the physician" about specific patients who need more than vancomycin, Pasqualone said.

In order to support this hands-on, "high science/high medicine sort of discussion," the company has a high ratio of medical science liaisons, who have had residencies or training in infectious disease. Theravance employs about four sales reps for each medical science liaison, Pasqualone noted.

Collecting Real-World Data

Theravance's pivotal trial programs for complicated skin and skin structure infections and hospital-associated and ventilator-associated pneumonia were "two of the largest cohorts ever studied in those indications," Pasqualone noted. But "we are getting real-world questions now," he continued, about off-label use and the complexities of issues like combination or sequential use that were not specifically addressed in the study setting.

Theravance also is actively seeking out real-world data through a 1,000-patient observational registry study called TOUR, in order to "compile as much data as we can," he said. "When we get a sufficient number of patients, we will mine the database."

The company also needs to keep on top of the development of resistance. "We collect microbiological data from every region in the U.S.," Pasqualone said. The company works with outside firms to collect isolates and test them against Vibativ, he explained. "We look at that on a yearly basis … to make sure no resistance is developing."

Broad Base Of Indications

Theravance's current focus on Vibativ is on expanding use to bacteremia. A Phase III program is ongoing for a broad bacteremia indication, and FDA is reviewing an sNDA for a claim of concurrent bacteremia in cSSSI and HABP/VABP patients with Staphylococcus aureus infection with a user fee goal in the second quarter of 2016.

Expansion to bacteremia, or bloodstream infection, could become a growth strategy for I.V. antibiotics. FDA approved Allergan PLC's cephalosporin Teflaro (ceftaroline) for concurrent S. aureus bacteremia in acute bacterial skin and skin structure infection patients on Aug. 31. Allergan also tried for a bacteremia indication in its initial broad new drug application for Avycaz (ceftazidime/avibactam), but it was not included in Avycaz' Feb. 25 approval.

The strategy responds to demand, according to Pasqualone. "We follow the lead of where the market is going," he said. The company's scientific advisory board said "one of the most confounding things" for physicians "is bacteremia," he reported. "If a patient is doing bad, they go through vancomycin, maybe daptomycin, then they are out of options."

If approved for bacteremia, Vibativ would be "the only branded antibiotic with three indications," Pasqualone noted. "That's important commercially."

That an antibiotic already approved for two major indications for I.V. antibiotics in skin infections and pneumonia, with good formulary acceptance and a third indication under review, is on track for sales of less than $15m for its second year on the market is a good illustration of the quandary facing antibiotic developers. The products are incentivized by government programs and are medically necessary, but the investment required to compete in the hospital market – on top of extensive clinical trials for approval – is a heavy burden for a small company.