The US Food and Drug Administration (US FDA) has issued guidelines for the pharma industry for developing drugs for acute bacterial sinusitis (ABS). The condition which is on the rise globally has led pharma companies to look into the nasal tract condition.

The purpose of this guidance is to assist sponsors in the clinical development of drugs for the treatment of acute bacterial sinusitis. The condition is an inflammation of the para-nasal sinuses as a result of the presence of a bacterial pathogen within the sinus space when the duration of illness is less than four weeks.

There have been a number of public discussions regarding the design of clinical trials to study ABS. It focuses primarily on the application of appropriate diagnostic criteria, timing of clinical outcomes, administration of  concomitant medications  and role of microbiological outcomes.

The regulatory authority has stated that the new drugs being studied for ABS should have non-clinical data documenting activity against the most commonly implicated pathogens associated with ABS. These include the  streptococcus pneumoniae, haemophilus influenzae, and moraxella catarrhalis.

Animal models of ABS have been developed, particularly for S. pneumoniae infection, and pathological and histological responses to antibacterial treatment have been shown in animals. Although these models may contribute to the scientific understanding of ABS and its treatment, the results should be carefully interpreted when being used to help design subsequent human trials. Because clinical trials can be conducted in patients with ABS, animal studies cannot substitute for the clinical trials that must be conducted to evaluate drug safety and efficacy, said the regulator.

The number of trials needed for approval of an ABS indication depends on the overall development plan for the drug under consideration. If the development plan for a drug has ABS as the sole marketed indication, we recommend that two adequate and well-controlled trials establishing safety and efficacy be conducted for that indication.

A single trial for an ABS indication may be appropriate if there is  data from other clinical trials demonstrating effectiveness in other respiratory tract diseases. The regulatory authority will also need additional supportive information like pharmacokinetic and pharmacodynamic studies demonstrating concentration of the antibacterial drug in the sinuses at a level expected to be active against the common pathogens causing ABS. For instance even the evidence of efficacy from community-acquired bacterial pneumonia (CABP) trials may be supportive of a single superiority trial because of the similar microbiology.

The disease course and treatment for ABS is of a short-term duration. Direct assessment of ABS symptoms to support a conclusion of treatment benefit in response to antibacterial drug therapies is readily measured. As such, there are no surrogate markers accepted by the FDA. Sponsors intending to  propose a surrogate marker for clinical outcome or the initial diagnosis of ABS should discuss this with the FDA early in the drug development process.

Antimicrobial drugs with clinically significant toxicity should not be considered appropriate for study of this indication unless treatment of a more seriously ill patient population is being considered.

From an India stand point, there are several companies engaged in the production of sinus inflation control. Therefore for the new drug development efforts, the USFDA guidance will serve as a platform for safety and efficacy of an investigational antimicrobial drug, said the industry sources.