Martha Bonino is the Director of Strategic Accounts at Clinipace Worldwide.

Dr. Lee Schacter, MD, Executive Medical Director of Oncology, and I recently hosted a webinar on Cancer Drug Development Using Molecular Pathology with Dr. Afshin Safavi, Ph.D., founder and Chief Scientific Officer at BioAgilytix, a provider of bioanalytical testing services.

In our first Q&A post, we addressed some of the questions we received around enabling technologies, and the second post addressed questions around the future direction of molecular profiling. Now in our third installment, we’ll be looking at issues related to FDA guidance and expedited approvals. If you have any additional thoughts or related questions to ask our experts, please share below in the Comments section.

Q #1: What are examples of the different types of expedited approvals?

Martha Bonino: As we discussed during the webinar, the FDA reviewed and provided guidance for four programs to facilitate and expedite development and review of new drugs, particularly for serious or life-threatening conditions. Examples of each type of expedited approval and treatment indications are included below:

  • Fast track
    • Coartem (artemether/ lumefantrine) – Malaria
    • Tykerb (lapatinib ditosylate) – refractory (including Herceptin), advanced or metastatic ErbB2‐overexpressing breast cancer
    • Sprycel (dasatinib) – chronic myelogenous leukemia (CML)
    • Arranon (nelarabine) – refractory or relapsed T‐cell acute lymphoblastic leukemia (ALL) or non‐Hodgkin’s lymphoma in pediatric patients under the age of 21
    • Atripla (emtricitabine; tenofovir disoproxil fumarate; efavirenz) – HIV
  • Breakthrough therapy
    • Arzerra (ofatumumab) – chronic lymphocytic leukemia
    • Zykadia (ceritinib) – metastatic non-small cell lung cancer
    • Zydelig (idelaisib) – relapsed chronic lymphocytic leukemia (CLL), relapsed follicular B-cell non-Hodgkin lymphoma, and relapsed small lymphocytic lymphoma (another type of non-Hodgkin lymphoma)
    • Keytruda (pembrolizaumab) – advanced or unresectable melanoma
    • Harvoni (ledipasvir/sofosbuvir) – chronic Hepatitis C
  • Priority review designations
    • Aciphex (rabeprazole sodium) – heartburn as a result of erosive GERD
    • Nymalize (nimodipine) – reduction of incidence and severity of ischemic deficits following subarachnoid hemorrhage
    • Gilotrif (afatinib) – non-small cell lung cancer
    • Tivicay (dolutegravir) – HIV
    • Gazyva (obinutuzumab) – lymphocytic leukemia (CLL)
  • Accelerated approval pathway
    • Zykadia (ceritinib) – metastatic non-small cell lung cancer
    • Imbruvica (ibrutinib) – chronic lymphocytic leukemia and mantle cell lymphoma
    • Arzerra (ofatumumab) – chronic lymphocytic leukemia
    • Xalkori (crizotinib) – non-small cell lung cancer
    • Iressa (gefitinib) – non-small cell lung cancer

Q #2: In terms of expedited approvals, information that can be used to support a “fast track” designation can include “evidence of nonclinical activity.” Can you please explain?

Martha Bonino: This terminology is meant to convey that the supporting data in a fast track designation request can be evidence of activity in:

  • a non-clinical (i.e., not in vivo human) model,
  • a strong mechanistic rationale from laboratory in vivo and even in vitro studies, or
  • pharmacology findings from animal studies.

The key point is that fast track designation has a lower barrier for evidence of potential efficacy in comparison to, for instance, breakthrough therapy, which requires supporting human clinical evidence.

Q #3: In light of the recent finalization of the FDA guidance on in vitro companion diagnostics, has Clinipace observed an increase in requests for advice and support of clinical trial assay/companion diagnostic-based trials?

Martha Bonino: Yes, most study sponsors are much more aware of the potential utility and need for companion diagnostic tools when considering their overall development plan.  While most requests are not related to standalone IVD development, our clients are considering — or, if not, we are advising them of — the implications to development timelines and the need for parallel development activities in order to target simultaneous approval of their product and companion diagnostic.

Be sure to listen to our webcast in its entirety to hear more about Cancer Drug Development Using Molecular Pathology. Thanks for tuning in!