A blog reader/Provectus shareholder informed me of it. Thank you.
In reading Herper's piece and visiting his Twitter feed @matthewherper, I found another Tweeter provided a link to a very BTD-related useful piece from middle market investment bank Leerink Swann entitled "Pre-ASCO Session on Breakthrough Therapy Highlights its Tangible Benefits." It makes for another good read.
In Leerink's research note, the authors have as their takeaways, from the "Breakthrough Therapies: The Regulatory Path" seminar during a pre-ASCO meeting led by Dr. Richard Pazdur, the head of FDA's Office of Hematology and Oncology Products (OHOP):
- An expectation for "knock your socks off" benefits in tough to treat patients;
- Closer, deeper, and highly iterative interactions between the companies and FDA with a "laser focus"on timely development and approval;
- Many of these drugs could get to market on single-arm studies alone;
- Patient numbers matter almost as much as effect size; and
- "Precision" medicine with a diagnostic component is preferred, particularly for the oncology division.
Using Pharmacyclics (NASDAQ: PCYC) as the best example of utilizing BTD, once you get one BTD for a compound, you may well get more, because the FDA presumably is comfortable with, among other things, the mechanism of action and scientific rationale of your drug compound: ibrutinib for relapsed/refractory mantle cell lymphoma (MCL), Waldenstrom’s macroglobulinemia (WM), and chronic or small lymphocytic leukemia (CLL/SLL).
The authors write that PCYC highlighted key qualifications for BTD including:
- Serious condition,
- Lack of standard of care and/or poor outcome of current treatment,
- Substantial improvement,
- Acceptable safety, and
- Scientific rationale for targeting a molecular driver.
An expectation for "knock your socks off" benefits in tough to treat patients. The ESMO 2012 poster presentation highlighted that Stage III subjects, where there only is the pseudo standard of care of chemotherapies dacarbazine (DTIC) or temozolomide (TMZ), experienced Progression Free Survival (PFS) of at least 9.7 months, a number which I think is longer and should again be highlighted at a European cancer conference in the fall. DTIC and TMZ PFS' are a couple of months or thereabouts.
Many of these drugs could get to market on single-arm studies alone. Single-arm sufficiency or near-sufficiency.
Patient numbers matter almost as much as effect size. More than 100: 20 cancer patients treated with PV-10 in a Phase 1 melanoma study, 80 in the Phase 2 study, and more than 80 patients enrolled in the Compassionate Use Program (although I cannot for PV-10.
"Precision" medicine with a diagnostic component is preferred, particularly for the oncology division. The imaging capability of PV-10's active pharmaceutical ingredient, rose bengal, is key to and a primary feature of its diagnostic advantage.
Scientific rationale for targeting a molecular driver. I presume this to be or contributed to by Moffitt's expansive murine and human study work.
Finally, the Leerink authors write: "A key component of the [BTD] program is that all aspects of the programs will be accelerated and a comprehensive discussion involves not only planned clinical trials generate substantial evidence to support accelerated or regular approval, but also plans for expediting manufacturing, co-development of diagnostic, and Expanded Access Programs."