The incidence of Clostridium difficile has increased significantly over the last two decades, due in part to the emergence of new, hyper-virulent strains. In recent years it has surpassed MRSA as the most common healthcare-acquired infection.
The current treatment options for C. difficile are mostly limited to antibiotics, and pharmaceutical companies are hoping to cash in by offering physicians alternatives for their patients. Vaccines are one such alternative, and are an important part of the current pipeline.
Figure 1: Key Pipeline Clinical Trials for C. difficile Vaccines
There are three key players in the race to bring the first C. difficile vaccine to market. Sanofi Pasteur is the longtime leader, with its candidate—a C. difficile toxoid A and B vaccine – set to complete a 15,000 participant Phase III trial in December 2017.
The race for second place is more intensely contested, and Pfizer and Valneva have been neck-and-neck for most of the last few years with their own developmental vaccines. Pfizer suffered an intermittent set-back in November 2014 when reported adverse effects at the injection site resulted in the halting of recruitment for its Phase II trial, giving Valneva the opportunity to edge ahead.
Recently, the tides may have changed.
With GlaxoSmithKline (GSK) deciding to waive its opt-in rights, Valneva has not yet found a new developmental partner to fund Phase III trials for its own pipeline candidate. Meanwhile, Pfizer, aided by being awarded FDA Fast Track designation, has pressed on with its own second Phase II trial.
In January, Pfizer announced that positive top-line results had been achieved in its second Phase II trial, leading the company to declare its intention to initiate Phase III testing in the H1 2017, allowing them to reclaim their strong position in the C. difficile prophylaxis pipeline despite their earlier setback.
The population expected to be targeted by these vaccinations is elderly patients at high risk of C. difficile infection, and most clinical trials have recruited patients ages 50 years or older. All three investigational vaccines have reported high seroconversion rates and acceptable safety profiles. With this limited differentiation between products, Sanofi is anticipated to benefit from the advantage of likely possessing the first-to-market vaccine.