As promised in February when Cempra Inc. completed its initial public offering (IPO), the Chapel Hill, N.C.-based biotech initiated its global Phase III trial of oral solithromycin (CEM-101), a first-in-class fluoroketolide antibiotic candidate, in patients with community-acquired bacterial pneumonia (CABP).

The double-blind, multicenter study expects to enroll about 800 patients with PORT-II to PORT-IV CABP in a head-to-head comparison of oral solithromycin at an 800-mg loading dose followed by 400 mg once daily for five days or once-daily oral moxifloxacin at 400 mg for seven days. The primary endpoint is noninferiority of early response at 72 hours.

Current FDA guidance for moderate to moderately severe CABP requires physicians to choose between combination therapy with intravenous antibiotics and/or oral administration of fluoroquinolone antibiotics, explained Prabhavathi Fernandes, Cempra's president and CEO. The former involves intravenous therapy – often requiring inpatient hospitalization – while the latter is associated with significant side effects, potentially including Clostridium difficile infection due to broad-spectrum activity associated with fluoroquinolones.

Phase II findings of oral solithromycin compared to oral levofloxacin in more than 400 patients with moderate to moderately severe CABP demonstrated comparable clinical success with fewer treatment-emergent adverse events for solithromycin (29.7 percent) than levofloxacin (45.6 percent).

"This will be the first time that a macrolide is being tested in monotherapy for moderate to moderately severe CABP," Fernandes told BioWorld Today.

Traditionally, macrolides have been used only in combination with another drug in CABP because of problems with resistance, she added.

"This is a paradigm shift in the treatment of CABP if we can succeed in this trial," she said.

The company expects to complete the trial in the first half of 2014. This year's severe flu season should ensure the timetable is met, since many flu patients develop CABP, Fernandes observed.

Cempra also has completed Phase I trials of an intravenous formulation of solithromycin and plans to move into a Phase III intravenous-to-oral step-down trial in mid-2013. If successful, the program could allow CABP patients to transition from intravenous monotherapy to oral monotherapy on the same drug, potentially reducing hospital lengths of stay and attendant costs to facilities, insurers and patients.

Once the oral and intravenous Phase III studies are complete, Cempra expects to file a new drug application with the FDA covering all CABP-related bacteria. Solithromycin has shown in vitro activity against a broad range of respiratory pathogens, including pneumococci, beta-hemolytic streptococci, staphylococci, Haemophilus, Legionella, Mycoplasma, Moraxella and Chlamydophila.

Few biotechs go it alone into Phase III trials, but, as the first macrolide in 20 years, solithromycin represents "a very well-differentiated product" with the opportunity to capture a broad swath of the CABP market – the number one cause of death due to infection, according to Fernandes.

"We licensed an early stage molecule from the bench, and it's exciting to move it to the bedside," Fernandes said. "We now have this last stretch of the marathon to run, which is the Phase III trial."

In the meantime, Cempra has published extensive data on solithromycin and demonstrated the compound has no pyridine sidechain, unlike Ketek (telithromycin, Sanofi SA), a macrolide that caused damage to the liver and other tissues. A second compound, fusidic acid, or Taksta (CEM-102), has helped Cempra to de-risk its pipeline. That drug, which is orally active against Gram-positive bacteria, including all S. aureus strains, already is approved in Europe, the UK and Canada. Cempra successfully evaluated a dosing regimen in a Phase II trial in patients with acute bacterial skin and skin structure infections and is conducting a Phase II trial in patients with prosthetic joint infections.

Cempra has exclusive rights to Taksta in the U.S., and incentives provided under the Generating Antibiotic Incentives Now Act will enable the company to extend that exclusivity, Fernandes observed.

"We expect to get this approved by the FDA in bone and joint indications, and we might actually look for an orphan indication," which would further extend exclusivity, she said.

In February, Cempra raised $50.4 million from its IPO by selling 8.4 million shares for $6 apiece. (See BioWorld Today, Feb. 6, 2012.)

Although the firm had hoped to raise $100 million from its IPO, in October investors ponied up another $25 million through a private placement. Despite running multiple late-stage trials, Cempra has not squandered the capital, reporting cash and equivalents of $51.6 million as of Sept. 30.

Cempra's shares (NASDAQ:CEMP) hit $9.56 in late June, after the company dosed the first patients in a Phase II of solithromycin in uncomplicated urogenital gonococcal infections. Since then, the stock has fallen back under $7, closing Wednesday at $6.12, down 17 cents.

Nevertheless, the biotech has sufficient funds to see it to the first quarter of 2015 and is reviewing additional funding opportunities through government grants and potential partners, according to Fernandes.

"Maybe we'll have to go to the public markets, but we hope there are other means of financing," she said.