Regulatory Focus™ > News Articles > FDA Draft Guidance on Pulmonary TB Seeks to Confront Drug Development Challenges

FDA Draft Guidance on Pulmonary TB Seeks to Confront Drug Development Challenges

Posted 08 November 2013 | By Alexander Gaffney, RAC 

The US Food and Drug Administration (FDA) this week released a new draft guidance on the development of new drugs intended to treat pulmonary tuberculosis (TB), a bacterially-transmitted disease that has seen increasing rates of drug resistance in recent years.

In a Federal Register announcement on the release of the draft guidance, FDA said its release was driven by three treatment challenges: increasing rates of antibiotic resistance, existing drugs interact poorly with those intended to treat other diseases like HIV, and drugs must now be taken over a lengthy period of time.

"Resistance to multiple drugs and the emergence of the human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) epidemic created new challenges in the management of tuberculosis," FDA explains in its guidance. "Drugs with new mechanisms of action, improved safety profiles, fewer drug-drug interactions (especially for patients needing concurrent treatment of HIV/AIDS), and use of shorter-course combination regimens are needed to manage tuberculosis."

Pulmonary Tuberculosis: Developing Drugs for Treatmentlooks to accomplish this goal by focusing on the development process of drug products for TB.

For example, under a section entitled "general considerations," FDA elaborates on the requirements for phase 2 clinical trials. Companies will be expected to include adult TB patients, but are cautioned that extrapulmonary diseases may require more extensive treatment and additional endpoints. In other patients who have extensively drug-resistant TB-sometimes referred to as multiple drug resistant (MDR)-two or more new investigational drugs should be considered, FDA said.

Efficacy will be based on either superiority or noninferiority. Safety, meanwhile, represents a more difficult set of considerations due to the frequent presence of comorbidities. The concomitant use of other antibiotics "provides additional challenges to the safety evaluation of an investigational drug," FDA writes. If a patient on multiple drugs experiences an adverse event, all drugs should be stopped at once, and the patient reintroduced to them "one at a time to explore which drug may be causing the adverse effect," the guidance recommends.

The remainder of the guidance delves into other aspects of clinical development, such as the characteristics of the trial population, inclusion and exclusion criteria, study designs, studies on specific populations, surrogate/primary/secondary endpoints, accelerated approval considerations and dosing.

Comments on the guidance are due by 4 February 2014.


Pulmonary Tuberculosis: Developing Drugs for Treatment

Federal Register


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