Pretty please, cherry on top..
We really, really need this drug. I hope the FDA approves it in short order. If not, I will be coming back to you for getting mobilized and pull off a massive letter writing campaign. Below are the comments I intend to make before the FDA panel on May 29th. Sorry if I sound a little stuffy and pompous – my audience this time is different than the usual rag-tag CLL patient crowd I hang out with.
I do not know if they will ask me any questions, I hope they do. Trust me, I am loaded for bear! If you have any drop dead comments or suggestions for changes do let me know. Otherwise, keep your fingers, eyes and toes crossed for all of us. I will report on how things went after I get back home.
Good morning ladies and gentlemen. Please allow me to introduce myself.
My name is Chaya Venkat. I am the Founder and President of CLL Topics Inc, an internet based organization dedicated to education and advocacy of CLL patients. With all humility but no exaggeration I can say there are very few CLL patients who have access to the internet and who can read English that have not heard of CLL Topics.
Today I speak before you on behalf of thousands of our members in this country and around the world who are anxiously following your deliberations. For the record, neither I nor my organization has any financial ties to any drug company. I have paid out of my own pocket for the opportunity to speak before you.
An unmet need
The day of targeted monoclonal therapy is tantalizingly close – but not quite there yet for CLL patients. Both Rituxan and Campath have major weaknesses when used as single agents. Ofatumumab represents a valuable option for patients stricken with this incurable cancer. I would like to share with you how patients see this drug fitting into their therapy options.
The FDA has recently approved Campath as a frontline drug in the treatment of CLL. Campath is undeniably powerful – except in patients with bulky disease, when it is contraindicated.
There is another very good reason why patients are leery about initiating Campath therapy early in the ball game. In addition to killing B-cells, Campath is also very good at demolishing T-cell counts. As researchers at the Karolinska Institute have demonstrated 1, many T-cell subsets remain a small fraction of their pre-therapy levels for many months. During this period of T-cell deficiency and long lasting neutropenia, patients are only too aware that they are dangerously vulnerable to opportunistic infections and even secondary cancers.
I realize Rituxan has not formally been approved as frontline or single agent therapy in CLL. But I am sure this panel is aware that many patients and their physicians currently use it in that setting – for lack of a better monoclonal antibody.
Unfortunately, as shown in an important paper out of M. D. Anderson 2, single agent Rituxan has very limited activity even in chemo naïve patients and at massive doses. In patients who have been around the chemo block more than once, single agent Rituxan is next to useless. Response rates are often in the single digits, and most of them are a partial response at best.
The Goldilocks scenario
Bottom line, looking at it from a Goldilocks perspective, Rituxan does not have enough oomph as a single agent, and Campath has almost too much killing power – or should I say too much poorly targeted killing power. We desperately need a new monoclonal antibody drug that has the admirable lineage specificity of an anti-CD20 monoclonal such as Rituxan, but one with increased killing power of a Campath – without unacceptable collateral damage of multiple bystander cell lines getting killed. Results of the clinical trial under discussion here suggest ofatumumab represent the golden mean we need badly.
Fludarabine refractory patients
The situation is bleak for patients who have relapsed after fludarabine containing therapy. The words “fludarabine refractory” are ominous indeed, reflecting as they do fewer therapy options, poorer response and scary survival statistics. CLL is definitely not a “good cancer” for these folks.
A recent M. D. Anderson paper 3 reported on the outcome of salvage treatment for patients who are fludarabine-refractory and are either refractory to alemtuzumab or ineligible for alemtuzumab due to bulky disease. Early death (within 8 weeks of commencing first salvage) occurred in 13% of patients, and 54% of patients experienced a major infection during therapy. Overall median survival was 9 months. Gentlemen, these are grim statistics.
Ofatumumab in fludarabine and Campath refractory patients
The new drug application before you looks at exactly this tough to treat patient population. While this ofatumumab study 4 is a single arm study, there is little doubt how poorly this patient cohort would have fared with, say, single agent Rituxan as control arm.
In stark contrast to all other salvage therapy options reported in the MDA paper 3, roughly 50% of these patients treated with single agent ofatumumab managed to get a decent response. Early death occurred in 3 to 4% of the patients, much smaller than the 13% quoted in the MDA study.
These are not just dry statistics, each percentage point represents living breathing patients. Median survival of 14-15 months after ofatumumab (compared to 6 months reported in the MDA paper for other monoclonal salvage options) means a beloved spouse or parent who is around for another 9 months – a very big thing for the families involved. I know what this means at a very personal level: my husband gained a precious couple of years of life due to ofatumumab therapy, giving cord blood stem cell transplants a chance to come up the learning curve. Two years earlier his chances of surviving a cord blood transplant would have been that much poorer.
I will not venture into why ofatumumab seems to work better, I will leave it to the experts among you. Whatever the reason, it is clear to our members that ofatumumab represents a next generation breakthrough anti-CD20 monoclonal drug that is desperately needed by CLL patients. Its performance as a single agent is impressive, even in tough salvage cases, but even more important will be its contribution to chemoimmunotherapy combinations down the road. For patients like my husband that develop serious hyper-sensitivity to chimeric Rituxan, this fully humanized monoclonal antibody is a godsend.
I would like to leave you with one additional thought. As consumers of healthcare all of us are aware of the cost of modern drugs. Rituxan costs an arm and a leg — and other body parts if the patient has no health insurance. Common sense tells me that having two anti-CD20 monoclonal drugs in the market place is a good thing. Competition has a salutary effect on pricing and product improvements. It is time we got a little competition going here.
On behalf of thousands of CLL patients I urge you to approve this new drug application. Please give our members access to ofatumumab. Our very lives depend on it.
Thank you for your time. I will be happy to answer any questions.
References:
1. Leukemia. 2004 Mar;18(3):484-90.
Cellular immune reconstitution after subcutaneous alemtuzumab (anti-CD52 monoclonal antibody, CAMPATH-1H) treatment as first-line therapy for B-cell chronic lymphocytic leukaemia.
Lundin J, Porwit-MacDonald A, Rossmann ED, Karlsson C, Edman P, Rezvany MR, Kimby E, Osterborg A, Mellstedt H.
Department of Haematology, Karolinska Hospital, Stockholm, Sweden.
2. J Clin Oncol. 2001 Apr 15;19(8):2165-70.
Rituximab dose-escalation trial in chronic lymphocytic leukemia.
O’Brien SM, Kantarjian H, Thomas DA, Giles FJ, Freireich EJ, Cortes J, Lerner S, Keating MJ.
Department of Leukemia, The University of Texas, M. D. Anderson Cancer Center, Houston 77030-4009, USA.
3. Leuk Lymphoma. 2007 Oct;48(10):1931-9.
The natural history of fludarabine-refractory chronic lymphocytic leukemia patients who fail alemtuzumab or have bulky lymphadenopathy.
Tam CS, O’brien S, Lerner S, Khouri I, Ferrajoli A, Faderl S, Browning M, Tsimberidou AM, Kantarjian H, Wierda WG
Department of Leukemia, The University of Texas, M. D. Anderson Cancer Center, Houston 77030-4009, USA.
4. ASH 2008, Paper 328
Ofatumumab (HuMax-CD20), a Novel CD20 Monoclonal Antibody, Is An Active Treatment for Patients with CLL Refractory to Both Fludarabine and Alemtuzumab or Bulky Fludarabine-Refractory Disease: Results from the Planned Interim Analysis of An International Pivotal Trial
Anders Osterborg, MD, PhD1, Thomas J. Kipps, MD, PhD2, Jiri Mayer, MD3, Stephan Stilgenbauer, Prof., Dr., med4, Catherine D Williams, MBBS, MRCP, FRCPath5*, Andrzej Hellmen, MD, PhD6*, Tadeusz Robak, MD, PhD7, Richard R Furman, MD8, Peter Hillmen, MBChB, PhD9, Marek Trneny, MD, PhD10, Martin J.S. Dyer, MA, DPhil, FRCP11, Swaminathan Padmanabhan, MD, MBBS12, Tomas Kozak, MD, PhD13*, Geoffrey Chan, MD14*, Randy L Davis, DrPH15*, Nedjad Losic, MSc16*, Charlotte A. Russell, MD, DMSC16, Magdalena Piotrowska, MD17*, Joris Wilms, MSc., Pharm16* and William G. Wierda, MD, PhD18*
62 comments on "Why Humax-CD20 must be approved"
Chaya,
Brilliant! If the FDA panel can’t understand this, they ought to be replaced. I sure hope there is no politics working against its approval. Good luck we are all rooting for you!
Michael Schwalm
Chaya
Really wonderful — keeping my fingers crossed, but I have my email list primed and ready if necessary.
Carol Kaelin
Chaya,
Excellent. In fact wonderful. Thank you, thank you
A couple quick comments.
in your first paragraph after your welcome statement, I would add a line on the number of visitors to CLL Topics. Let them know your reach is for real and enormous
Somewhere in your text, I would also call attention to the critical need for ofatumumab in the patients who can’t tolerate or are allergic to Rituxan, a mouse based antibody. You can get personal and powerful about this one.
Finally a typo in the third to last paragraph: “As consumes of healthcare” should be consumers of healthcare.
Be well
Brian
What a super bit of work! I trust that the panel will receive it in the way it deserves. Meanwhile, as a UK patient, I will keep it up my sleeve for NICE – our FDA equivalent!
Best wishes for the presentation Chaya
Lawrence
Your speech is to the point…looks good. Could the Obama appointee(s) to this agency have any oversight in consideration of our concerns toward the individual FDA employees making the decisions? Who are they? After your speech, do we need to be specific toward these individuals with our personal expressions? Chaya, you’ll have them in the palm of your hand.
William Bates
As a patient who is violently allergic to Rituxan, I am waiting and hoping that Humax-20 gets approved and soon! Like Carol (above) I am ready to email, phone, and contact however many people it takes to get this approved.
Cyndee Giebler
Thank you Chaya — good luck!
And to my fellow “Updates” members: Once again, please consider contributing what you can to financially support this important cross-country trip on our behalf. Let’s do our part.
Godspeed Chaya.
Jim
Dear Chaya,
Thank you for continuing to fight on our behalf. As always, you have made a compelling argument.
Good luck!
Lynda Lemberg
Thanks Chaya, you are so good – in every sense of the word.
Very good Chaya, hope all goes well as it will benefit many CLL patients.
good luck
Chonette
2 months post SCT
As per Jim’s request here’s my $100. Take a rest at Disney World after you wow those who must understand. Chuck
Great work as usual and continued success. Ron
Jim and Chuck – thanks for the suggestion and follow through.
My donation is on it’s way too. MicheleB
(3 years now in an FCR remission, but really anxious to know what comes next when this is over)
Chaya,
This is EXCELLENT!! I agree with Brian-let ’em know we are out here listening and reading on the internet. May the FDA realize that there is no such thing as a good cancer!
Chaya,
Brilliant and excellent!! I had tears in my eyes while reading this.
Thank you so much again and again.
Blessings,
Rita
Chaya — I echo the bravos above. And yet…I see one chink in your armor (our armor). What will FDA commissioners and staff be thinking when they hear a patient advocate? “OK, brace yourself. Get out the hankies.” Your statement disabuses them of their prejudice that they are dealing w/ emotionalism cloaked in clinical/scientific lingo. Until the end: “On behalf of thousands of CLL patients I urge you to approve this new drug application. Please give our members access to ofatumumab. Our very lives depend on it.” I would add: ” — not because our members are grasping at straws, but because a dispassionate reading of the science argues the case for approval coldly and convincingly.”
If any FDA listeners are not hearing your unique, science-based patient perspective, perhaps that small addition will hoist them by their own petard.
I have no ego invested in my suggestion. If you and others disagree, I willingly defer to your judgment. You are a master communicator, and this note is carrying coals to Newcastle. …. Go get ’em! — Jon
Chaya
Much good luck, they’re a tough bunch. I know the X-VP at J&J who used to do this and she had an awful time.
Let us know what happened.
John
Chaya- This looks great. Thank you again. I hope I can hang on using Rituxan as monotherapy until Humax is approved.
Malcolm Airst
Chaya,
Excellent presentation. Wondering if it would make sense to remind the committee that our CLL cohort is getting younger and younger which is another rationale to have more approved therapeutic options??
Break a leg (not really!)
Chaya:
Thank you so much for all you do for the CLL community-you are truly our ANGEL!!
Brian
Rooting for you! Go get ’em.
Heidi, CLL spouse
Chaya,
Well done. Thank you for shouldering the task of representing the cll community.
Jim
Very well stated and best of luck on the trip
Michael
Chaya… My husband and I are relatively new to your column. Our Oncologist “guessed” that my husband originally had CLL, based on just some basic bloodwork, but then after the CT, Pet, and Bone Marow, it came back conclusive that he has Follicular Lymphoma. However, part of his treatment is Rituxan. We found out on the first two treatments that he seems to be VERY ALLERGIC to the mouse protein. He broke out in major hives… So we, too, are anxious for Humax to be approved….
Does anyone in this blog know the answer to this? When the FDA approves a drug, do they just approve it for a particular disease (e.g., CLL), or do they approve it across the board, for whatever diseases could benefit from it? THANKS SO MUCH FOR YOUR GREAT WORK, Chaya! Sue
Susanandcarl:
Humax has been in clinical trials for follicular lymphoma as well – but I do not know where it stands in terms of FDA approval. I will ask around.
The good news is that while the FDA may “permit” use of Humax for only CLL, once it is commercially available any doctor can prescribe it for his / her patients, for any other cancer. As an example, Rituxan is not formally approved for CLL as a single agent frontline therapy, but it is approved for follicular lymphoma. But thousands of CLL patients nevertheless use Rituxan as frontline and single agent.
Moral of the story, once the drug is commercially available because the FDA has approved it for something, anything, the cat is out of the bag and all of us will have access to it. Keep your fingers crossed, I hope your husband will have access to it soon.
A different subject but one that is getting a lot of attention from our members (and a lot of emails to me) …
The laypress has a number of articles published in the last day or so regarding green tea and leukemia. These articles are all based on an interview granted by Dr. Tait Shanafelt of Mayo Clinic, the researcher who conducted the green tea trial that CLL Topics funded and sponsored. It would have been kind of nice if they had mentioned that little fact, don’t you think? I worked hard to get that trial going, and you worked hard to fund it. Oh well. Just so long as the research got done, I am happy.
The Mayo article appears in Journal of Clinical Oncology this week. I will review it for you guys as soon as I get back from Orlando.
Chaya,
They did mention CLL Topics update. This from Medical News Today…
“The study was sponsored by Mayo Clinic, the CLL Global Research Foundation, CLL Topics (including contributions by individual CLL patients) and the Commonwealth Foundation for Cancer Research.”
What the article does not state is any change in overal survival and should untreated patients pursue this at risk of becoming refractory to it down the road. Still confused.
Jeff
I will be the patient representative at the May 29th FDA drug review meeting of HUMAX-CD20(ofatumumab) whose trade name is Arzerra. I will be a voting member of the review committee along with other professional medical members. I was also on the review committee for Genasense a few years ago. The rules of engagement are not what many of us would choose or expect. I have learned that drug companies do not always play their cards in the most effective manner at these meetings and that the FDA operates under a prescribed set of procedures and rules which can be confusing to an outsider. This particular application is for accelerated approval as opposed to normal approval and as such has certain special considerations. Whether this drug would be a good addition to the CLL arsenal is not the paramount issue. There are all sorts of other technicalities such as how well run was the clinical trial supporting the drug application, the evaluation criteria etc. all of which come into play.
My current comments are limited by a confidentiality agreement but that will not apply after the meeting. I know you can anticipate a full report from Chaya afterwards and I will be free then to share my two cents as well.
Diane MacKinnon
Grannybarb left big shoes to fill, but you are her Cinderella. How I wish she could have met you. You are a blessing!
-Kathy
Actually, I did have the pleasure of meeting Granny Barb. She came to Sedona in 2001 and we had a good visit. She was the first of her breed and all of us who came after her owe her a debt of gratitude.
Chaya,
Thanks so much for your tireless work here. Lives do depend on these approvals. I do not pretend to understand the approval process for these new drugs. Like most things in life it seems there is a small group making the decisions for many who have no skin in the game.
Best of luck
David
Chaya,
Diane answered my question of whether there might be women on the committee. Perhaps Ladies and gentlemen might be a better greeting than Gentlemen. Whatever, I don’t know who better to represent us at the hearing. Give ’em hell!
Fred Hummel
Chaya… Well, thank you so much for your very quick response! That is great information you provided. Now, may I ask another question for either you, or any of your wonderful friends that check in daily to this column… I am sure you have SEEN IT ALL, so maybe you can help me… This is in regard to Rituxan…. On my husband’s first treatment, they spread the Rituxan over two days… The first day, he had a few reactions.. low BP, and then mild hives. They stopped the infusion that day. On the second day, they slowed down the infusion rate, and he was able to finish it up (though it took 5 hours). On his second treatment (a week ago), he immediately developed a very bad case of hives all over, and they had to stop it altogether for this treatment – and just gave him the chemo. We have a meeting with our doctor on Friday to determine “what to do next” — to discuss options as to how we can get this Rituxan into him. He has taken all the appropriate pre-meds (by infusion the day of the treatment). We are at a top-notch center in Atlanta – so these nurses really know what they are doing… I am wondering if you can offer any insight here. Do people sometimes take Steroids well a few days in advance of the Rituxan to soften the blow – as opposed to just getting them infused that day? Whatever info you, or any of your readers, could offer, would be greatly appreciated! THANKS SO MUCH…. Sue
dmackinnon
Diane makes some good points. There are some non trivial issues here, and that is why I think approval of ofatumumab is not a slam dunk. I have been reviewing the FDA briefing document submitted by the company to make myself familiar with the application and all the gory details.
The best we can do is try to do the best we can do. But if the FDA rules absolutely positively require a double arm study before they approve the drug, we might be in trouble. That is when we try to take a different approach to skinning the cat, get the old consumer movement going by way of letter writing, phone calls, emails etc. Our patient community has not done a stellar job of complaining up to now. May be it is time to change that.
I will be sure to post contact information, what to say, who to say it to etc when and if it becomes necessary for us to become the squeaky wheel. Keep your powder dry until then. Who knows, this may be when we grow up and become a patient community they have to respect.
Chaya
You go girl! Thank you so much for what you are undertaking. I may not be there in person to support you, but I am with you in spirit. Mary
Good work and good luck on Friday.
Carolyn Bookspun
Dear Chaya,
As always, I appreciate your sustained interest and hard work on behalf of the CLL community. I’m looking forward to hearing how things go at the meeting – I’m sure you will do a great job. I also look forward to your review of and link to the green tea story.
Go get ’em,
Kathy Chase
Great! Is the appearance open to the public? I would love to be there to meet and support you.
Jennifer Kupper
Orlando
Good Luck Friday! We so appreciate you representing us on this important issue–Coy needs this drug ASAP- he is taking revlimid for the second time right now after having to discontinue treatment for 3 months due to revlimid side effects-we have no idea how long he will be able to take it this time– and his doctor has no suggestions for further treatment after revlimid other the a splenectomy! It would be great to try Humax with the revlimid RIGHT NOW!!
Thanks again!
Nancy and COY
Best of luck – you have my support. However, you may consider to address some of the concerns that are appearing on the news wires more directly:
“FDA said it “does not consider the patient population studied in the BFR group as meeting the regulatory standard for having an unmet medical need,” and added that the “FDA has determined that GSK will need to conduct a comparative study in order to support approval in a patient population … who were only required to be refractory to one drug”.
I am new to this and do not know what the regulatory standards are, but it should be clear from your presentation that there is an unmet need. It may also be good to state it should be compared directly to Rituxin, and it is certainly comes out favorable in terms of response and less side effects.
Thomas
another link with more information:
http://www.reuters.com/article/healthNews/idUSTRE54Q4G120090527
Thomas
Chaya==You make a clear and cogent argument; I can’t imagine anyone doing it better. Thanks!
Loaded for Bear! We have no doubt. We’re sending a contribution, as well as our invincible vibes :-)
xo Barb & Blair
jdk1
I do not know for sure, but I think it is open to the public. It would be nice to have some friendly faces in the audience!
I have read all your suggestions carefully and incorporated most of them into my comments. Talk to you all next week. I will not be taking my laptop with me on this trip and therefore will be out of reach for a few days.
if not too late, where and what time
Chaya,
The CLL Community cannot thank you enough for speaking before the FDA. You are the guardian angel for all of us. You are right-If they do not approve this important MAB we must mobilize a massive campaign to get it approved.
I think the outcome of the Green Tea trial at Mayo will prove to be another very imporant tool in the arsenal, and we would not have it withut you. I have been taking my 2000mg daily with the blessing of my 2 oncologists for close to 2 yrs now and my numbers have improved, I feel well, my liver function is fine and I remain in stage 0 4 yrs after my dx.
Thank You!
Chris
Chaya,
I am sure this comes from all of us in the CLL community. We can’t thank you enough for all you are doing to help us with our daily struggle with this disease. I wish you all the best of luck and faith in reaching the FDA to approve Humax-20. God Bless you. Your speech is absolutely fantastic. I live in Dunnellon, central Florida. Not too far from Orlando. If you have the particulars as to where it is some of us who live here would like to be your cheering section.
Good luck.
Anita
Thanks Chaya for all you have done & continue to do. Give ’em hell! We have tremendous faith in you!
Thank you Chaya and good luck with your comments at the meeting. Sounds like we’re going to need all the help we can get to get this passed.
Thanks Chaya, you are always there for us.
To add to the discussion about cost, our Rituxan has always been in the $4500 per infusion ballpark. Now that the patent is running out (has?) we find that the bill has jumped to $7000 per infusion. Competition will surely help this temptation to overprice.
Beth
As always Chaya, Thanks. I’m facing tretment again and will be discussing clinical trials w/ my doc. You lucid expinations are always helpful in my decision making process.
always Chaya,helping poor people for finding suitable treatment for refractory fludara your help is greatly appreciated
e great
best of luck to you and to us! As far as I know, no monoclonals for the treatment of CLL are yet approved in Ontario, Canada. Approval in the US would, I believe, speed up approval here as well and thereby quite possibly extend the lives of many CLLers in Canada.
Wishing you success!
Ingo Viebrock (Martin)
Chaya, Thank you so much for everything you’re doing on behalf of the people that live with this disgusting disease. I was terrified, and deeply depressed until I found CLL Topics and learned how to fight and get healthy despite this cancer.
Safe trip and much success. We are all behind you.
dee
Concerning the comment above from Chaya on 5/27 about the Mayo Clinic green tea study (in which I was one of the participants), today’s (June 1) Minneapolis newspaper ran a page-1 article on the study. Here’s a quote from the article:
“Because no drug company was interested in funding the studies, [Dr.Tait] Shanafelt [the CLL expert who is the principal investigator of the study] turned to a patient group, called CLL Topics, which raised nearly $400,000 for this and other research.”
Great job, Chaya!
Jim
Correction–the article in the Minneapolis paper is Sunday, May 31, not June 1.
Here’s a link to the article’s web page:
http://www.startribune.com/lifestyle/health/46554437.html
Harley
Dentymic;
As who had a severe allergic reaction to initial treatment with Rituximab (Vasculitius) I applaud your efforts to get this drug approved.I’m just starting Fludarabine and Cytoxin mix therapy (without any Rituxin). In between I’ve been trated twice with chlorambucil.
I’m ready to write letters , e-mails etc. if need be.
Thanks for all you continue to do for those with CLL.
Thank you I’am on campath right now and praying for a new breakthrough.
Never a dull day. I just saw the press release from GSK and Genmab that the FDA has delayed final approval of Humax-CD20 (Arzerra, ofatumumab) by another 3 months. Previously it was thought we would have a decision no later than August 1. Here is quote from the companies, the new decision date is October 31.
GlaxoSmithKline (NYSE: GSK) and Genmab A/S (OMX: GEN) today announced that the United States Food and Drug Administration (FDA) informed the companies that the agency has extended the action date for the ofatumumab BLA application by three months.
The BLA was submitted on January 30, 2009 and was granted priority review by the FDA. Under priority review, the FDA sets the target date for a decision at six months, rather than the standard 10 month review. The three month extension will allow the agency to review additional chemistry and manufacturing data submitted on June 5. The new action date for the BLA is October 31, 2009.”
The news and the FDA’s inactions/delays on Arzerra is very disappointing for me. I failed FCR on first try, probably refractory already, approaching SCT and need the Arzerra option for some sort of remission prior to transplant. As far as I’m concerned, the FDA process is total useless. It’s a wonder we have any approved drugs.
pvplunk1:
Don’t give up just yet!
We will wait until October 1, 2009. Hopefully Arzerra will be approved. If not, that is when we get proactive with our letter writing campaign and see if we can change the ballgame. We won’t know how much influence we have until we try. Right?
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