The U.S. Food and Drug Administration has posted new draft guidance that will guide drug and medical device manufacturers that aim to develop treatments for “the underlying pathophysiology and structural progression” of osteoarthritis (OA).
The U.S. Food and Drug Administration (FDA) has posted new draft guidance that will guide drug and medical device manufacturers that aim to develop treatments for “the underlying pathophysiology and structural progression” of osteoarthritis (OA).
In its short draft guidance, which was first reported by Regulatory Affairs Professional Society (RAPS), the FDA said that to date, approvals for treatments of osteoarthritis have been “based on patient-reported outcome measures that assess pain and function.” However, the FDA said that treatments that aimed at the underlying pathophysiology and structural progression of the disease have so far been elusive and constitute an unmet medical need. The guidance will not address the improvement of OA symptoms such as pain or functional impairment. The FDA said those are important outcomes and will be addressed in a future guidance.
The new draft guidance was issued days after Regeneron and Teva posted positive Phase III results for fasinumab as a treatment for osteoarthritis (OA) of the knee or hip. At 16 weeks patients experienced significantly less pain and also showed significantly improved functional ability from baseline.
As the draft guidance moves forward, the FDA noted that device makers and drug manufacturers should consider several structural endpoints issues to include in a finalized document. The FDA said makers should be aware of the multifactorial and complex etiopathogenesis of the disease. Additionally, they should note the “well-recognized discordance between structural changes and signs/symptoms/function.” Also, the lack of standard definitions of disease progression, as well as the absence of endpoints to reliably assess the ability of a product to alter OA disease progression should all be noted.
“Because of the complex and variable pathologic changes through which OA impairs function and leads to long-term disability and/or joint replacement, at this time it is unclear what magnitude of change in structural endpoints would translate to a clinically meaningful benefit to patients,” the FDA said in the draft guidance.
Because of that, no structural endpoints have been used for traditional or accelerated approval in OA to date, the FDA added.
In order to accept structural endpoints for OA, the FDA said there should be “substantial confidence” based on clinical evidence or a comprehensive understanding of the disease process and mechanism of action where such an endpoint will “reliably predict an effect on the clinical outcomes of interest.”
“The ultimate goal of treatments related to inhibition of structural damage or targeting the underlying pathophysiology associated with OA is to avoid or significantly delay the complications of joint failure and the need for joint replacement, and also to reduce the deterioration of function and worsening of pain,” the FDA said.
As the FDA pushes forward on new OA guidance, it asked for input from drug and device manufacturers to address the considerations.
