7/12/22, 4:04 PM
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`Breakthrough Therapy | FDA
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`Breakthrough Therapy
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`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).
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`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.
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`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:
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`An effect on an established surrogate endpoint
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`An effect on a surrogate endpoint or intermediate clinical endpoint considered reasonably
`likely to predict a clinical benefit (i.e., the accelerated approval standard)
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`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
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`A significantly improved safety profile compared to available therapy (e.g., less dose-
`limiting toxicity for an oncology agent), with evidence of similar efficacy
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`A drug that receives Breakthrough Therapy designation is eligible for the following:
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`All Fast Track designation features
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`Intensive guidance on an efficient drug development program, beginning as early as Phase
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`1 O
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`rganizational commitment involving senior managers
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`Breakthrough Therapy designation is requested by the drug company. If a sponsor has not
`requested breakthrough therapy designation, FDA may suggest that the sponsor consider
`submitting a request if: (1) after reviewing submitted data and information (including
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`https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy
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`1/2
`
`UPenn Ex. 2008
`Miltenyi v. UPenn
`IPR2022-00853
`
`

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`Breakthrough Therapy | FDA
`7/12/22, 4:04 PM
`preliminary clinical evidence), the Agency thinks the drug development program may meet the
`criteria for Breakthrough Therapy designation and (2) the remaining drug development
`program can benefit from the designation.
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`Ideally, a Breakthrough Therapy designation request should be received by FDA no later than
`the end-of-phase-2 meetings if any of the features of the designation are to be obtained. 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.
`
`https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy
`
`2/2
`
`UPenn Ex. 2008
`Miltenyi v. UPenn
`IPR2022-00853
`
`