When there are few good options left..

In my last article I wrote about the withdrawal of Campath as  a marketed drug for CLL.  This was such a blatantly cynical decision, based on nothing more than profit.  I am not a huge fan of Campath.  It has a high degree of immune suppression associated with it, especially in terms of drastically reduced T-cell counts for many months after completion of therapy – which in turn leaves patients vulnerable to opportunistic infections, secondary cancers etc.  So, why am I upset about Campath getting pulled from the market for CLL folks?  Because Campath is one of very few drugs that is thought to work to some degree for patients with the dreaded 17p (TP53) deletion.  Are there any others?  Yes, but it is a frighteningly small list.  Flavopiridol is one of them.  This drug has been in clinical trials for more years than I can remember – and it is still stuck there.  The only place you can get it is at Ohio State University, under the watchful eye of Dr. John Byrd.  Over the years, it has been shown this drug is not easy to administer – serious risk of tumor lysis syndrome –  and hence no one outside of OSU currently uses this drug.  Another option with possible benefit is Revlimid (lenalidomide).  However, initial hopes that the drug will work with 17p deleted folks have been somewhat dampened when a large scale study showed less than expected response in this subset of patients.

Hope on the horizon

Kinase inhibitors are all the rage these days.  In particular, ibrutinib (PCI-32875) has demonstrated some remarkable activity in CLL, with no major adverse effects demonstrated thus far.  I have written about this drug several times thus far, you can find the earlier articles by searching for the key words in the search box at the top right hand corner of our home page.

What is most exciting about ibrutinib is that it seems to have remarkable efficacy even in high risk patients, especially those with 17p deletions.  This is tremendously hopeful news.  However, phase-3 trials have just gotten underway and it will be some time before it even comes up for FDA review for approval.  Phase-2 clinical trials presently going on are pretty much sold out, and in any case each of these trials has a long list of inclusion criteria that limits who can get in.  Double arm phase-3 trials have the added complication of randomization into either of the two arms.

I have had to face this heartbreaking question several times in the past few months:  what do I tell patients with aggressive CLL with the 17p chromosomal deletion, who cannot get into one of the ibrutinib trials underway, and who cannot afford to wait for future trials and definitely cannot wait for the drug to become commercially available?  This drug may give them a much needed lifeline, perhaps set them up with a good enough remission that allows them to get into a transplant program.  Or it may give them a couple more years of high quality of life with their families.  Who can put a dollar value on that?

Compassionate use access programs

Initiating a compassionate use access program is not a simple process.  But it can be done, if the company in question actually wants to do it. It takes money, people resources and the desire to reach out to the patient community.  Ibrutinib is owned by Pharmacyclics.  Janssen pharmaceuticals, a subsidiary of Johnson & Johnson has purchased the rights to the drug in the USA.  Pharmacyclics is not a large company.  But J&J is  very large, more money than god as they say, and with massive financial resources,  people, and of course, lawyers to protect its crown jewels.

I figured that while it may be difficult for Pharmacyclics to initiate a compassionate use access program because of their size, it should be well within the reach of  an industry leader such as J&J.  Fortunately for me, one of the folks at J&J wrote to me, to see if they can work with our patient community – they were interested in working with me on some sort of a survey, along the lines of the very large patient feedback survey we did with Mayo Clinic.  I took the opportunity to raise with J&J the question of compassionate use access program so that some of our patients who desperately need ibrutinib but cannot get into the clinical trials have a path forward.  Here is the relevant  part of my letter to the company:

There is one important topic that I would really appreciate your bringing it up with your senior management. It has to do with compassionate use access to ibrutinib. I fully understand the need to conduct clinical trials with well defined inclusion criteria. Scientific experiments and the results from them are only as credible as the rigor with which the experiments are conducted – I am enough of a scientist myself to accept that wholeheartedly. We need well conducted clinical trials in order to get this valuable drug through the FDA approval process and last thing we need is hiccups along the way because of poorly defined clinical trial protocols and “squishy” methodology in data collection.

 But at the same time, there are always individual patient stories that need to be addressed, if at all possible; people who fall between the cracks as it were, who do not fit the exact profile demanded by the inclusion criteria of clinical trials. Well publicized compassionate use access programs are a hugely important way of reaching out the patient community, a way of establishing good faith on behalf of the pharmaceutical company. J&J is a large company, with the human and financial resources needed to manage such a program, a corporate culture that does not look only at profits or stock price. If anyone can take the lead in establishing a badly needed new paradigm for working with the patient community, it is going to be companies such as J&J. There is common ground and much to be gained here, but we need vision and leadership to make it happen. If there is anything I can do to help initiate / progress such a program, I would be honored to do so.

On a very personal note, my husband was granted compassionate use access to ofatumumab back in 2006, well before its commercial availability. He had developed severe allergic response to the murine components of Rituxan and I am convinced ofatumumab gave him a precious couple more years of high quality life. He was a very high visibility patient in the CLL community and I think it made a difference to how Genmab was viewed by patients. I was delighted to testify on behalf of the patient community before the FDA scientific panel as they deliberated approval of ofatumumab – perhaps my testimony made a difference.

How did J&J respond to my heartfelt plea?  I heard back from my initial contact at J&J.  No dice.  He could not even get anyone at J&J to talk to me on the phone.  The best he could do, he said, was give me the general phone number at J&J that I can call, where I can get the public domain boilerplate that some lawyer at the company has drafted on the subject of compassion.  That, is if I succeeded getting through the telephone tree in the first place, I suppose.  To say that I am disappointed is putting it mildly.  I am steamed!


It seems the last time I wrote about ibrutinib and in my editorial comments I discussed the potential bleeding risk, someone at the Yahoo finance group message board on Pharmacyclics picked up my article and it created a minor brouhaha – heck, it may have even caused a very temporary downward blip on the stock price.  But I will be the first to admit I am no expert on that front.  I do not own a single share of Pharmacyclics or J&J, nor do I plan to in the future.  And I doubt anything I can say or write will ever have much of an impact on a company of the size of J&J.  I got a bit of an ego sugar high when a few financial analysts called me to ask if I would consult with them – for a fee of course.  The deal would be that I give them a heads up before publishing the next article.  How many different ways would I be compromising my promises to this patient community if I did that? No thank you.  I don’t need money that badly.

Does J&J have a history of reaching out directly to the patient community when it comes to their oncology drugs?  As it turns out, it is one of the more proactive companies on that front.  Does anyone remember the direct-to-consumer television  ads the company took out on their drug Procrit?  This is an epo drug, a red blood cells growth factor.  If I remember correctly, the advertisement would show an elderly gentleman, moping around because his red blood cell count was too low to let him go out and play with his grandson.  Or dance at his daughter’s wedding.  Whatever.  Then he gets Procirt, and lo and behold, there he is out playing ball and the soul of the party at the wedding.  I may not have remembered the exact story-line, but you get the gist.  Heck, they may even have had violin music as background,  these TV ads were clearly expensive, well produced and slick affairs.

The only problem was that epo growth factors had tell-tale adverse effects when used heavily in cancer patients.  I was one of the very first people to raise the alarm on this front (as far back as 2003!!).   My article was titled “The dark side of epo“.  It is now well established that Procrit and similar epoetin  red blood cell growth factors can act as growth factors for cancer as well, increasing risk of cancer progression and relapse.  We now have pretty strict guidelines on how these drugs can be used.

I don’t blame pharmaceutical companies for trying to make money, even lots of it.  Cancer patients with poor red blood cell counts would have been a huge market for expensive red blood cell growth factor drugs.  I just wish J&J is as proactive in reaching out to the patient community when it comes to establishing compassionate use access programs – or even bothering to talk to the patient community about it.  Outreach should be the norm, not the exception only when the company is trying to sell us something.

The perfunctory brush-off I got is nothing personal, I am well aware of that.  But it is one more sour note in the long story of pharmaceutical industry’s inability to establish good-faith and two way communications with the very patients that they will be marketing to down the road.  How about a little bit more respect, folks?  

As for me, my apologies.  I am truly sorry I was not able to do better for you guys.  If some of you have ideas on how to breakthrough this typical logjam, I am only too willing to listen.