It looks like a risk associated with some approved antibiotics may not be a concern for Cempra’s (CEMP) own late-stage candidate, solithromycin. Cempra announced on Tuesday morning that the macrolide antibiotic demonstrated no negative effect on QT intervals (QTc), a marker of potential cardiovascular issues, at single intravenous doses of 800mg in a 48-patient study. 800mg is nearly twice the threshold at which solithromycin has shown a therapeutic effect.
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart’s electrical cycle, a representation of depolarization/repolarization of the ventricles. A prolonged QT interval is a marker for potential arrhythmia, and in the worst scenarios, sudden death.
With this study, Cempra is allaying fears that solithromycin, like macrolides that came before it, might have a prolonging effect on QTc and increase the risk of cardiovascular events. All approved macrolides (including erythromycin, clarithromycin, telithromycin, and azithromycin) have been associated with QT interval prolongation, and just last year the label for azithromycin, the most commonly prescribed macrolide, was updated to include this risk (even some fluoroquinolones have been associated with QTc prolongation). Combined with solithromycin’s apparent lack of toxicity, an issue associated with solithromycin’s best commercial comparator, telithromycin (Ketek), investors are giving the company credit for what continues to look like a safer, new antibiotic.
PropThink wrote about Cempra in detail at the end of last year, calling it a stock to own in 2014. You can read the report here. CEMP is still an attractive buy, having come down from its 52-week highs.
Note that the ongoing phase 3 SOLITAIRE-IV trial tests solithromycin in IV form at 400mg, which is why Cempra calls the 800mg dose used in the QT interval study “supratherapeutic.” In the trial, 48 subjects were enrolled in a three-way randomized dosing sequence cross-over design to receive 800 mg of intravenous solithromycin; 400 mg of oral moxifloxacin, which was used as a positive control (plus saline); or IV saline as a negative control. No QT effects were seen with solithromycin, assessed by a core lab, and the study’s assay sensitivity was confirmed by the QTc prolongation observed with moxifloxacin The study met the requirements for a Thorough QT study by ICH E14 guidance.
The QTc results not only indicate that solithromycin is safe, but give it an edge on the number of existing – and generic – approved macrolide antibiotics. Remember that solithromycin is a 4th-generation macrolide/fluoroketelide.
The phase 3 SOLITAIRE-IV study, testing a solithromycin IV-to-oral step down therapy in CABP, will read out by the end of this year. SOLITAIRE-ORAL, testing an oral formulation, will read out at mid-year.
Catch up on Cempra in PropThink’s previous coverage.
In connection with CEMP, PropThink has taken a long position.
