Closer to Approval for CLL? Ibrutinib Receives a Third Breakthrough Designation from the FDA for 17p deleted Patients

Here is the first part of the official press release on the third breakthrough designation for ibrutinib. This one is close to home.

The news is important, not only because it means there is another reason to believe the wonder pills will be in drug store near you next year some time, but because insurance, at least at first, will likely only pay for the designated indications, without putting up a fight.

The good news is however limited in its scope. It is only for CLL/SLL with 17p del. I don't know if the percentage of the cells that lack the short (think p for petit) arm of their 17th chromosome has been defined that will be needed to qualify. We know that 17p del tends to play more nicely at lower percentages. Not sure if the FDA gets down to that level of detail and I hope they leave that decision to a discussion between us and our doctors, as we do now when considering therapy.

What we do know is that this does not mean breakthrough designation for all of us with CLL. At least not yet.

Will it be used off label for others with CLL? Most cancer drugs are and one that in the studies so far appears to be as safe and efficacious as ibrutinib should be no exception. Who pays will be the bigger issues.

On a personal note, as one with small population of 17p deleted CLL cells, this is particularly good news, as I would have an option should my trial close or I need to leave it.

SUNNYVALE, Calif., April 8, 2013 /PRNewswire/ -- Pharmacyclics, Inc. (PCYC) announced today that the U.S. Food and Drug Administration(FDA) has granted an additional Breakthrough Therapy Designation for the investigational oral agent ibrutinib as monotherapy for the treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) patients with deletion of the short arm of chromosome 17 (deletion 17p). Patients harboring a deletion within chromosome 17 generally have poor response to chemoimmunotherapy and have limited treatment options. The presence of deletion 17p is one of the worst prognostic factors in patients with CLL.

In February 2013, FDA granted Breakthrough Therapy Designations for ibrutinib as a monotherapy for the treatment of patients with relapsed or refractory mantle cell lymphoma (MCL) and as a monotherapy for the treatment of patients with Waldenstrom's macroglobulinemia (WM), both of which are also B-cell malignancies. Ibrutinib is jointly being developed by Pharmacyclics and Janssen for treatment of B-cell malignancies.

The Breakthrough Therapy Designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases where "preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development." The designation of a drug as a Breakthrough Therapy was enacted as part of the 2012 Food and Drug Administration Safety and Innovation Act. Pharmacyclics, together with Janssen, is working with the FDA to determine the implications of this Breakthrough Therapy Designation to the ongoing and planned development and the FDA filing requirements for the use of ibrutinib in CLL patients with deletion 17p.

The FDA Breakthrough Therapy Designation for ibrutinib in CLL patients with deletion 17p was based on data from pre-clinical and clinical studies where ibrutinib as a monotherapy was used to treat patients with this disease. Ibrutinib has the potential to improve the outcome in this serious and life-threatening disease which has a poor prognosis. In addition, Pharmacyclics and Janssen have recently initiated a Phase II study of ibrutinib in patients with CLL deletion 17p, RESONATE" -17, which is a single-arm, open-label, multi-center trial using ibrutinib as a monotherapy in patients who have deletion 17p and who did not respond to or relapsed after at least one prior CLL treatment (a high unmet need population). The primary endpoint of the study will be overall response rate. This global study opened this year and Pharmacyclics plans to enroll 111 patients worldwide.