Oncolytics Biotech Inc T.ONC

RE:RE:RE:Clinical Trial Size in Orphan and Rare Diseases

[Noteable]

Orphan  drugs can be divided into 4 mutually exclusive categories: (1) approved for a single rare disease (sole orphan), (2) approved for multiple rare diseases (multiorphan), (3) initially approved for a rare disease and subsequently approved for a nonrare disease (orphan first), and (4) initially approved for a nonrare disease and subsequently approved for a rare disease (non–orphan first).

ONCYs pelareorep potentially falls into categories 1, 2, and 3 for marketing approval, and then potentially in the non-orphan/non-rare category after approval in one or more of the above categories with subsequent life-cycle management and product indication expansion. 

In the process of acieving an Accelerated Approval a company would first seek FDA Breakthrough Therapy status which follows end-of-phase-2 FDA meetings if any of the features of the designation are to be obtained.  Breakthrough Therapy designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s). 

To determine whether the improvement over available therapy is substantial is a matter of judgment and depends on both the magnitude of the treatment effect, which could include duration of the effect, and the importance of the observed clinical outcome. In general, the preliminary clinical evidence should show a clear advantage over available therapy, which ONCY is demonstrating in mPDAC and SCCA, using identifiable/established surrogate endpoints and clinically significant biomarkers.

For purposes of Breakthrough Therapy designation, clinically significant endpoint generally refers to an endpoint that measures an effect on irreversible morbidity or mortality (IMM) or on symptoms that represent serious consequences of the disease. A clinically significant endpoint can also refer to findings that suggest an effect on IMM or serious symptoms, including:

• An effect on an established surrogate endpoint
• An effect on a surrogate endpoint or intermediate clinical endpoint considered reasonably likely to predict a clinical benefit (i.e., the accelerated approval standard)
• An effect on a pharmacodynamic biomarker(s) that does not meet criteria for an acceptable surrogate endpoint, but strongly suggests the potential for a clinically meaningful effect on the underlying disease
• A significantly improved safety profile compared to available therapy (e.g., less dose-limiting toxicity for an oncology agent), with evidence of similar efficacy

Breakthrough Therapy designation is requested by the drug company. 

Because the primary intent of Breakthrough Therapy designation is to develop evidence needed to support approval as efficiently as possible, FDA does not anticipate that Breakthrough Therapy designation requests will be made after the submission of an original BLA or NDA or a supplement. FDA will respond to Breakthrough Therapy designation requests within sixty days of receipt of the request.

This notwithstanding, ONCY has already obtained Fast Track  designation for pelareorep in advanced or metastatic pancreatic cancer.

https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy