Irbrutinib has been approved in CLL

IBRUTINIB HAS BEEN APPROVED IN CLL
IBRUTINIB HAS BEEN APPROVED IN CLL
IBRUTINIB HAS BEEN APPROVED IN CLL
IBRUTINIB HAS BEEN APPROVED IN CLL
IBRUTINIB HAS BEEN APPROVED IN CLL
IBRUTINIB HAS BEEN APPROVED IN CLL


Here is the press release from ASCO:



From the American Society of Clinical Oncology
In cooperation with the Food and Drug Administration (FDA), and as a service to our members, ASCO will periodically distribute information about newly approved therapies for cancer patients.  This helps FDA to inform oncologists and professionals in oncology-related fields of recent approvals in a timely manner.  Included in the email from the FDA will be a link to the product label, which will provide the relevant clinical information on the indication, contraindications, dosing, and safety.  In sending this information, ASCO does not endorse any product or therapy and does not take any position on the safety or efficacy of the product or therapy described.  The following is a message from the FDA's Office of Hematology and Oncology Products Director, Dr. Richard Pazdur:

On February 12, 2014, the U. S. Food and Drug Administration granted accelerated approval to ibrutinib (IMBRUVICA, Pharmacyclics, Inc.) for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.  Ibrutinib previously received accelerated approval on November 13, 2013 for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy.
The approval in CLL was based on the results of a multi-center, single-arm trial of 48 patients with previously treated CLL. The median age was 67 years (range, 37 to 82 years) and 71% were male. All patients had a baseline ECOG performance status of 0 or 1. The median time since diagnosis was 6.7 years and the median number of prior treatments was 4 (range, 1 to 12 treatments).  Ibrutinib was administered orally at 420 mg once daily until disease progression or unacceptable toxicity.

The efficacy results demonstrated a 58.3% overall response rate (95% CI: 43.2, 72.4) as assessed by an independent review committee.  No complete responses were observed. The response duration ranged from 5.6 to 24.2+ months; the median was not reached.

The safety profile of ibrutinib for patients with previously treated CLL was consistent with observations in the mantle cell lymphoma clinical trial.  The most common adverse reactions reported in the CLL clinical trial (occurring in greater than or equal to 20% of patients) were thrombocytopenia, diarrhea, bruising, neutropenia, anemia, upper respiratory tract infection, fatigue, musculoskeletal pain, rash, pyrexia, constipation, peripheral edema, arthralgia, nausea, stomatitis, sinusitis, and dizziness.

As a condition of this accelerated approval, the FDA required that the sponsor submit results of randomized clinical trial(s.) In January 2014, Pharmacyclics notified FDA of the early stopping of the RESONATE trial by the Data Monitoring Committee (DMC) based on favorable results of a planned interim analysis. RESONATE, a phase 3 clinical trial, randomized patients to either ibrutinib or ofatumumab.  Patients entered on this trial had previously treated CLL or small lymphocytic lymphoma (SLL) and were not considered candidates for treatment with purine analogue-based treatments.  The trial was reported to demonstrate an improvement in progression-free survival and overall survival.  

The recommended dose and schedule of ibrutinib for patients with CLL is 420 mg (three 140 mg capsules) taken orally once daily.
Full prescribing information is available at: 
http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203147s000lbl.pdf

Management of High Risk CLL

There are a variety of organizations out there that help disseminate education material.  I have recently had the option to work with a group called "Clinical Care Options."  I gave a seminar for them at ASH on Diffuse Large B Cell Lymphoma and more recently they asked me to put together a module for patients with high risk CLL (link here).

"High Risk CLL" isn't a really tightly defined term although there does seem to be some consensus that it may define a group of patients at high risk of dying from their disease within a few years.  It can refer to patients with high risk genetic markers such as 17P deletion or mutations like BIRC3.  It can refer to patients who fail to achieve a really good response to therapy and have high levels of "minimal residual disease."  It can also refer to patients who relapse quickly after initial therapy.  Though there is probably quite a bit of overlap between these sorts of patients (ie. the patients with bad markers, fail to respond well and relapse early) those relationships are only still just becoming more clear (see my post on CLL prognosis).

Anyhow, I wanted to provide you with a link to the education module.  You need to sign up for a free account which takes about 10 seconds to do.  I hope it is a good tutorial for physicians who take care of patients with CLL.  I acknowledge that it is fairly technical for patients who are new to CLL but each of the concepts have been presented previously on my blog.

Thanks for reading

Copayment Assistance

I had the opportunity to visit Pharmacyclics headquarters today.  It was the first time I've been there since 2007 when I was helping them design their original first in human phase I protocol (read part of that story here).

Thanks to all the nice people who took time out of their day to chat!  It was fun to see the excitement brewing within a company that has developed a really remarkable drug.  It felt to me a lot like the fun anticipation of Christmas Eve with kids (except with well behaved adults of course).

One thing I learned will be of considerable interest to a bunch of patients, so I thought I would throw a quick blog post up while awaiting my flight (back to a snowy Eugene... Lord help me).

Many of you know that the new drugs are pretty darn expensive.  I've posted about drug costs previously for the interested reader.  I think a lot of patients are reasonably apprehensive of the cost of care.  For a drug that costs over $10K/month, that can potentially put the hurt on you really fast.

Fortunately the team at Pharmacyclics / Jannsen have put together a pretty fantastic copayment assistance program.  Many drug manufacturers have such a program and sometimes these can remain stubbornly hidden to patients who have to fork out the cash every month for their drugs unaware that funding assistance may be available with a little work.

There are really two different mechanisms depending on what sort of insurance you have.  For NON-MEDICARE patients (ie. the Blue Cross, Aetna, etc), you can apply for a grant if you are taking your ibrutinib for an FDA approved indication (see post on off label drug use).  Currently that is just mantle cell lymphoma, though the approval in CLL is eagerly anticipated by many.  Once approved in CLL, the grant program will cover that disease as well.

Long story short, a NON-MEDICARE patient should be able to get their drug for $25/month under most circumstances when using the copayment assistance program.  The link to that program is here.

Medicare patients have a slightly more difficult situation, but by no means impossible.  Since CLL frequently affects older patients, quite a few patients are likely to fall into this category.  Medicare has policies that make it more difficult for manufacturers to provide copayment assistance.  The work around is for the companies to make large grants to third party organizations like Lymphoma and Leukemia Society that can then make structured grants to patients.  The copayment assistance webpage can help direct patients to such organizations.

US Healthcare is an ungodly mess when it comes to who pays for what, what things cost, and who gets paid for it - but it is nice to know the patients are not getting caught in the crossfire on this one.

Thanks for reading