FDA Issues Two Final and One Draft Drug Development Guidances
The US Food and Drug Administration (FDA) issued two final guidances meant to assist sponsors looking to develop products to treat or prevent acne vulgaris and hypogonadotropic hypogonadism, as well as a draft guidance on developing drugs to treat or prevent cytomegalovirus in transplant patients.Specifically, these guidances discuss drug development considerations for the particular diseases, including preclinical factors, clinical trial enrollment criteria, study design and efficacy endpoints.
Acne Vulgaris
For sponsors looking to develop products to treat acne vulgaris, more commonly referred to as acne, FDA says sponsors should look to enroll patients with a minimum number of both inflammatory and noninflammatory lesions and with a baseline score on an investigator’s global assessment (IGA) severity scale consistent with the number of lesions.
FDA also says that sponsors should conduct multiple randomized, double-blind studies of potential treatments against a placebo, and says that assessment of the drugs should be focused on their effect on lesions on the face.
For a primary endpoint, FDA says sponsors should assess the absolute change in lesion counts and use the percentage change in lesion counts as a secondary endpoint.
The guidance finalizes a draft version released in 2005, which FDA says has been streamlined and reformatted to feature a bulleted list of recommendations.
Hypogonadotropic Hypogonadism
The next guidance focuses on development considerations for drugs intended to treat male hypogonadotropic hypogonadism associated with obesity and other conditions.
The guidance finalizes a draft version issued in January and reflects advice from advisory committee meetings in 2014 and 2016 on testosterone therapy and hypogonadotropic hypogonadism.
FDA says the guidance is largely the same as the draft version aside from editorial changes and a clarification that the guidance does not apply to testosterone or testosterone esters being developed for traditional testosterone replacement therapy.
According to the guidance, sponsors should carry out randomized, double-blind, placebo-controlled studies to demonstrate a clinically meaningful improvement in one or more symptom or sign of hypogonadism.
FDA also says that patient-reported outcomes (PRO) “may play a central role in establishing efficacy because they provide direct evidence of how patients feel or function,” but says that improvements in biomarkers such as changes in muscle mass that are not established surrogate endpoints are not sufficient to demonstrate efficacy.
Cytomegalovirus in Transplant Patients
Cytomegalovirus is a common virus in the beta-herpes virus group, thought to be present in 40-80% of the US population.
For patients with a normal immune system, the infection is typically benign and self-limiting. However, the virus can cause complications and increased morbidity in patients with compromised immune systems, such as transplant recipients or AIDS patients.
In the guidance, FDA focuses specifically on development considerations for products intended to treat or prevent cytomegalovirus in patients who have undergone solid organ (SOT) or hematopoietic stem cell transplantation (HSCT).
According to FDA, cytomegalovirus is also the most frequent opportunistic pathogen to infect transplant patients, with seronegative recipients being at higher risk for developing an infection if they receive a transplant from a seropositive donor.
While there are currently five drugs approved to treat or prevent cytomegalovirus, FDA says that new, less toxic therapies are needed as recent research has identified emerging viral resistance to existing treatments.
As such, the 34-page guidance discusses preclinical and clinical considerations, including the use of cytomegalovirus DNAemia as a surrogate endpoint, for prophylaxis, prevention and treatment of cytomegalovirus in both SOT and HSCT recipients.
Acne Vulgaris: Guidance, Federal Register Notice
Hypogonadism: Guidance, Federal Register Notice
Cytomegalovirus: Guidance, Federal Register Notice