Why does it take so long to get new drugs approved?
It has been several years since I first wrote about Humax-CD20 (technical name “ofatumumab“) – the next generation anti-CD20 monoclonal antibody that we hope will give Rituxan a run for its money. We are still waiting for this new drug to become commercially available. With a little luck, Humax-CD20 will get FDA approval sometime in 2009.
I probably know more about how this drug works in CLL patients than just about any other layperson. My husband PC got compassionate use access to this drug when he developed significant allergic reaction to Rituxan. He got Humax-CD20 by the boatload. But for his fortunate access to Humax-CD20 therapy I expect PC would have had to face transplant decisions a couple of years earlier – a prospect that I dreaded since cord blood transplants for adults were in their infancy back then.
Will the FDA approve Humax-CD20 for CLL?
What is holding up the FDA approval process for Humax-CD20? How is it that the company has yet to file for approval? The answers are both simple and complex. So much money rides on new drug development that companies have to take a very cautious approach to not blowing their chances, not getting in front of the FDA too soon, before they have their ducks in a row.
What impresses the FDA? The short answer is development of a drug that works better than presently available options in the really tough nut cases. Especially in indolent cancers such as CLL this makes a lot of sense. Early stage CLL patients with good prognostics hardly need any treatment at all, hence the recommendation to Watch & Worry. Even when they do need a little something to kick the CLL back a couple of notches, these early stage and “smoldering” types have many therapy choices available to them. It is hard to demonstrate the cojones of a new candidate drug in a such a crowded field.
How about the other end of the spectrum, the guys who have been around the chemo block more than a couple of times, patients who no longer respond to fludarabine or even Campath? What about the cases where the lymph nodes and / or spleen are so enlarged that they have no chance of getting a good clearance with Campath? Remember, conventional wisdom says Campath is not likely to work on nodes that are “bulky”, larger than 5cm across. As we wrote about in an earlier article, these “double refractory” patients have few options. None of the available “salvage therapy” options (barring a stem cell transplant) hold much hope of producing long term remissions. I strongly urge you to re-read our review of Refractory CLL if you are not familiar with the study. But you may want to get a stiff drink to help you with the bleak statistics, especially if you tend to have weak knees and don’t deal well with bad news. Don’t say I did not warn you!
A strategy that might work with the FDA (I hope!)
Genmab has been very smart in their choice of patient cohort for testing the efficacy of Humax-CD20 as a single agent. Their inclusion criteria mandated that the patients (1) must have had several cycles of prior chemotherapy under their belts (2) they must be refractory to fludarabine (3) they must also be refractory to Campath orthey must be ineligible for Campath therapy because their bulky nodes are larger than the 5cm cutoff.
Presently these patients do not have many good options. Majority of them are in late Rai stages and I expect over their CLL journey many of them have acquired more than their share of high risk chromosomal (FISH) defects. As we know by now, single agent Rituxan works – sort of – in chemo naïve patients. It gets no respect at all in patients with high risk profiles or those who have had multiple rounds of chemotherapy. As for double refractory patients, attempting Rituxan therapy as a single agent would be a waste of time in the vast majority of cases.
Genmab’s strategy is to see if Humax-CD20 can give these folks a better therapy choice. If the clinical trial demonstrates improved overall response rates, longer remissions and longer survival times using Humax-CD20 with fewer adverse effects in this group of people, the company stands good chance of getting the coveted FDA approval.
Breaking news at ASH 2008 Conference
The results of the single agent Humax-CD20 trial in refractory CLL patients is published in this year’s ASH abstracts (abstract # 328). You can read the full abstract by clicking on the link. The long author list has some of the best CLL experts in this country and Europe. The trial was conducted at several centers. While it is not a double arm or randomized study (there was no defined control group), the large cohort size (138 patients), expert panel and the multiple centers give credibility to the results.
Did Humax-CD20 hit it out of the ballpark?
OK, I hope at least some of you dutifully clicked on the link, got a little cross-eyed sorting out the statistics and now you are ready for my far more readable cheat-sheet analysis. I thought so. I will break down the results into four sections:
- Profile of patients recruited for this study
- Their response to Humax-CD20 single agent therapy
- How does this compare with other choices available to such patients?
- What was the “cost” of Humax-CD20 therapy?
Last but not least, I will give you my two cent editorial opinion – cheap at the price, as they say. You will have to draw your own conclusions, make up your own mind whether you agree with me or not. That is both your right and your obligation to yourself.
Yep, Genmab recruited a tough bunch of patients for their Humax-CD20 single agent study, just as advertised. If you see yourself matching this profile (as my husband PC did), you too would have a certain sense of urgency in getting better therapy choices approved in real time.
I wish I can give you a straight thumbs-up or down on the evaluation of the results, but the devil is in the details. For starters, I would have liked to see many more Complete Responses (there was a single patient with a CR in the “BFR” group). On the positive side of the equation, between 86 – 90% of the patients got some level of response or at least managed to keep their disease stable – no mean task for this crowd. Single agent Rituxan would not have seen even single digit overall response rates in this patient cohort.
The remission duration was also short, of the order of 8-9 months, before treatment was needed again. Bummer.However, as most of us know, even early stage and chemo-naïve patients on single agent Rituxan therapy need repeat cycles of Rituxan every 6-12 months. The million dollar question is whether Humax-CD20 therapy is repeatable in refractory patients. The official word on this is not available. But from a strictly anecdotal perspective, PC repeated his Humax-CD20 treatments for a total of 3 cycles, starting April 2006. While he did not get the coveted CR, each time he got a good partial response with squeaky clean blood counts and significantly smaller lymph nodes. Each time the nodes started acting up again in 6-8 months.
So much for the duration of the remission, but even more important to us chickens, how long did the patients live? The median survival was roughly the same for both DR and BFR groups, about 14-15 months. This is tough news to swallow, especially if you identify with the profile of these patients. I think it is fair to say Humax-CD20 is no magic bullet capable of CURING late stage CLL patients. We still have to look to stem cell transplants to achieve that goal, at least for now.
Comparing apples to apples
Actually, the following is not exactly kosher comparison, it is more like comparing granny smith apples with golden delicious apples. More or less the same, but not quite – someting to remember as you look at the comparison below.
Facing reality head on, how did the Humax-CD20 survival statistics compare with presently available therapy options for this patient cohort? I am willing to bet that would be one of the criteria the FDA will be looking at as they make their decision. Unfortunately, while this was a large scale study with a goodly size patient cohort conducted at multiple reputable centers in the USA and Europe, its design is not the gold standard of clinical trials – it is not a double arm randomized study with a well defined and tightly matched patient control group. Since we do not have a defined control group to use for comparison, I will do the next best thing: compare these results with prior studies with similar patients – more or less.
The graph above comes from a very recent article (2007) and a credible research team (M. D. Anderson). The abstract is given below, and you can find the full length review we did of it on our flagship CLL Topics website.
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 and Stem Cell Transplantation, MD Anderson Cancer Center.
The natural history and outcome of salvage treatment for patients with fludarabine-refractory chronic lymphocytic leukemia who are either refractory to alemtuzumab (“double-refractory”) or ineligible for alemtuzumab due to bulky lymphadenopathy (“bulky fludarabine-refractory”) have not been described. We present the outcomes of 99 such patients (double-refractory n = 58, bulky fludarabine-refractory n = 41)undergoing their first salvage treatment at our center. Patients received a variety of salvage regimens including monoclonal antibodies (n = 15), single-agent cytotoxic drugs (n = 14), purine analogue combination regimens (n = 21), intensive combination chemotherapy (n = 36), allogeneic stem cell transplantation (SCT; n = 4), or other therapies (n = 9). Overall response to first salvage therapy other than SCT was 23%, with no complete responses. All four patients who underwent SCT as first salvage achieved complete remission. 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 survival was 9 months, with hemoglobin < 11 g/dL (hazard ratio 2.3), hepatomegaly (hazard ratio 2.4), and performance status >/= 2 (hazard ratio 1.9) being significant independent predictors of inferior survival.
PMID: 17917961
Since the patients in the Humax-CD20 trial and the salvage therapy results reported in the M. D. Anderson are not exactly matched, you must take the comparison with a grain of salt. However, the patients in the M. D. Anderson trial are also double refractory (or Campath ineligible because of bulky nodes), and therefore folks facing the same thorny therapy decisions.
The MDA reports overall response rate of 23%, significantly lower than the 51-44% reported for the Humax-CD20 trial. The survival statistics in the MDA study are broken out into the various therapy options open to the patients. I expect in their case the “Monoclonal Ab” refers mostly to Campath therapy – no one would realistically expect single agent Rituxan to do much for these guys. Like you I was stunned to see how steep the drop-off was for the “Monoclonal Ab” group. Fully 12 out of the 15 patients were dead by 10 months. Ouch. That hurts.
Now for the half full glass perspective: Except for “PA Combination” (purine analog combinations such as FCR, PCR, CFAR and similar alphabet soup drug combinations) with 16 month median survival in the MDA study, Humax-CD20 single agent therapy beat all of the other much more aggressive therapy options with its 14-15 month median survival. As I said above, this is not a strictly legit comparison since the groups were not exactly matched and computer randomized. You will have to make your own call whether the comparison is valid on this absolutely crucial point.
Risks and rewards
What was the price tag in terms of adverse effects? I hope by now I have got you thinking of the balance between risks and rewards whenever you evaluate therapy options. So, what is the cost of Humax-CD20 in terms of adverse effects? Did patients get enough of a bang for their buck?
As a comparison point, let us see how the refractory CLL patient group did in the M. D. Anderson study referenced above, using presently available therapy options. Here is a quote from the abstract: “Early death (within 8 weeks of commencing first salvage) occurred in 13% of patients, and 54% of patients experienced a major infection during therapy.” Wow. Sounds pretty grim to me.
What did the Humax-CD20 trail have to say on the subject of adverse effects?
The infusion related side effects are something we have all come to expect with any monoclonal antibody therapy. Likewise, the anemia and neutropenia are within acceptable levels.
But the Grade 3-4 infection rate for Humax-CD20 is more like Campath than Rituxan. In fact, this was a point of discomfort for me right from the beginning and during the course of a long conference call we tried (more or less unsuccessfully) to convince the company to include robust guidance for prophylactic medications in their clinical trial. Last but by no means least I am deeply concerned about the 5 patients (4%) that died within 8 weeks of initiating Humax-CD20 therapy. Sure, 4% early death is better than 13% reported in the MDA study, but it is still too high for comfort. Hopefully as we learn more about how best to administer Humax-CD20 and protect patients while we are doing it, these numbers will come down. There was a similar learning curve for Campath, early users faced a host of high risk opportunistic infections until we learned how to protect patients with prophylactic antiviral drugs.
Given the Humax-CD20 cohort and the MDA patient group are not exactly matched, it is hard to draw solid conclusions. At first blush Humax-CD20 seems associated with fewer adverse effects, but this has to be confirmed in additional clinical trials with matched control groups. I would also like to see if the adverse effects reported for Humax-CD20 single agent use can be improved with appropriate protection of patients with antiviral and antibacterial drugs.
Editorial
I am glad to see how many top rated CLL experts were on the author list of this important paper. Just about each of the authors has been quoted at one time or the other on CLL Topics, each of them represents the best of the bunch. Too bad I was unable to attend the ASH conference this year – I would have liked to listen to the full presentation. Perhaps I will be able to get hold of the presentation slides.
What is the bottom line? Does Humax-CD20 represent an improvement over Rituxan? I think the answer is YES. Single agent Humax-CD20 did far better than we can expect from single agent Rituxan in a refractory CLL patient population. Will this be enough to get FDA approval? I hope so.They may have a problem with the fact that this was not a double arm study with well matched control group. Will the company be sent back to the drawing board to conduct another long clinical trial with the necessary bells and whistles? Would the company’s more recent combination of Humax + fludarabine + cyclophosphamide (compared to the presently available FCR combo) in chemo naive patients fill in the blanks? If the FDA thinks there are too many unanswered questions that may delay commercial availability of the drug for several more years. That is a delay we can ill afford. All the more reason why the patient community may need to get involved, see if we can get the FDA to listen to our perspective on things. I will let you know when /if it is time for you guys to get into an activist mode. Heck, the new boys in Washington DC say they want our input, perhaps we should take them at their word.
Looking over the patient profile in the Humax-CD20 study I was struck by the fact more than half of them had prior exposure to Rituxan. It has been suggested that multiple infusions of Rituxan gradually leads to selection of CLL cells that no longer respond to the drug. The mechanism is thought to be development of traits that block the killing power of complement. Now, as we described in our review article on what might make Humax-CD20 a smarter monoclonal than Rituxan, we highlighted the importance of complement mediated cell death in Humax-CD20 therapy. That raises an interesting question: will patients who have not been previously treated by Rituxan and therefore had not developed resistance to complement mediated cell kill respond better to Humax-CD20 therapy? My husband PC had pretty good response to Humax-CD20, but would he have had even better response if he had not had multiple cycles of Rituxan prior to trying Humax-CD20? Does prior flirting with Rituxan spoil patients for Humax-CD20?
Here is another little something to look forward to. Remember that bit of excitement about “beta-glucan“, derived from baker’s yeast? There were several excellent articles on the subject of how beta-glucan may get around complement inhibitory proteins that cancer cells develop as a way of defending themselves from complement’s killling power. My friend the late Gordon Ross of the University of Louisville died of stomach cancer before he saw his research bear fruit. But I am happy to tell you that two other high powered researchers have picked up the trail – Dr. Clive Zent of Mayo and Dr. George Weiner of University of Iowa. And here is the icing on the cake: CLL Topics is providing the seed money to the tune of $20K to get this important project off the ground. Down the road I hope we will have better answers to the question whether monoclonals such as Rituxan and Humax-CD20 will work better in combination with beta-glucan, because the combination may prevent CLL cells from avoiding death by complement.
All in all, interesting developments on the Humax-CD20 front. Now we have to be patient some more and keep our fingers crossed this important drug is soon approved by the FDA for general use in CLL. What do you think? I look forward to your comments, questions and suggestions.
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27 comments on "Does Humax-CD20 Work?"
Chaya,
First of all, thank you so much for your return with a full head of steam to the most informed and comprehensive resource for us.
I read and cried at a distance with all other readers of CLLTopics this summer. Your personal loss, as you know, reverberated so far. And selfishly, the fear of losing your knowledge and analysis.
I had many questions on the HUMAX-CD20 study from ASH, and you have answered many. Responses and durations are, on the one hand, so dismal-sounding. But the key is whether it is BETTER than alternatives and will do better in combos.
I am sending in my donation tonight, so you can continue this vital activity. Thank you, and may 2009 be better than 2008 and bring you unexpected joys,
Helene
Dear Chaya,
It’s absolutely wonderful to see your writings again – and on your spanking new site!
This was a particularly interesting article to me, as Kelly, my dear 73 year old husband (having miserable prognostic markers) is presently finishing up FCR. Knowing that he will probably not enjoy as lengthy a remission as those having snazzy markers and that subsequent rounds of FCR are generally not as successful as the previous, we are already giving thought to other possible treatment plans.
While other new options may be available by the time Kelly’s disease escapes remission (and given his age), at this time we are considering bendamustine and Humax CD-20 as a possible sensible combination. It will be interesting reading other comments to your very well done piece on Humax CD-20, Chaya, and I look forward to further writings from you on the topic.
Jan
Chaya, welcome back, many thanks for all your service, past and prospective. I shall contribute promptly. Roland
Morning, Chaya…
And a (hopefully) happy and prolific new year to you and everyone here! I know I am going to enjoy 2009…but more on that in a moment.
First, I am glad to see that you choose to keep up this great service. I was diagnosed with CLL in June of 2004, and immediately found your website. I have been discussing the information I find here with my doctor at the University of Rochester Medical Center (we made arrangements to communicate by email, and in addition to just passing general knowledge, I usually get the COMPLETE report on my tests emailed to me within hours of their completion.)
Your website has kept me on top of this disease better than any other means that I have found, and even introduced some interesting aspects of it for my doctor to think over and comment on.
In the hope that you and Radha can continue this great service as long as possible, I will be sending in a donation as soon as I finish this comment. Small though it will be, I hope it can help.
In the risk of going off the topic of Humax somewhat, I do have some personal good news that I’d like to share with everyone.
Initially, The FISH and BMB tests showed that I had pretty much the same flavor CLL that PC had. Positive Zap 70, CD 38, etc. My doctor asked me to address a second year medical student lecture regarding my CLL. The preliminary speaker used my test results, the then current size of my “visible” nodes and finally slides of my bone marrow for show and tell. He concluded that I had a pretty grim prognosis. But I enjoyed talking to the students and making a video of some of it anyway!
We started my first treatment in August of 2007 when my ALC got up around 80,000 (80.0) and my jaw nodes were of the chipmunk variety! We used pentastatin, cyclophosphamide and rituxamab instead of fludaribine, as I had had a bout with hemolytic anemia the previous year. She feared the Fludaribine may have reactivated the anemia.
We finished the Rituxan in January this year (2008) and immediately started a Campath regimen. Dr. L did bring up the possible use of Humax at that time as well. And I thought she was going to use it, but she decided on three IM shots a week of Campath which we completed in March.
From August 2007 until the present day, I have been taking daily doses of anti viral, anti fungal and anti bacteria drugs (and green tea capsules…325 mg of EGCG twice a day).
So far, the results have been better than either of us expected! I have had absolutely no significant side effects throughout this time, during the treatment or after (I got the hiccups for a couple of days following the Rituxin, and a slight rash the day after each Campath shot that lasted only about 8 hours.) Although my nodes have not disappeared completely, now, after 9 months, the ones under my jaw are still small enough that they can’t be seen, and appear to STILL be shrinking…the axillary and inguinals are gone…at least by palpating.
I feel better than I have in years and have a very positive attitude about all this now.
My blood work shows that the ALC is still increasing at a very slow rate, and after 9 months has yet to reach low “normal”. It started at 0 in april, and did get to 500 (0.5) last month and if is still there this month I can stop the prophylactics! Dr. L is still mentioning the possible use of Humax when I need another treatment …I’ll keep you all informed.
I do keep all my blood test results in a spreadsheet, and doing a trend analysis of the ALC, I shouldn’t need treatment again for at least 4 more years! Of course, that’s a linear trend…the actual ALC increase is probably exponential, but hey…I can dream, can’t I!
My friends and family are continuously surprised that I am so well versed on the disease and it’s treatments, and I only have CLL Topics (and you, of course) to thank for that.
I promise, future comments won’t be as long! And once more…Happy 2009 to everyone…and keep thinking positive thoughts.
Now…off to Paypal…
Harley Dixon
Harley:
I am glad the PCR + Campath chaser has worked so well for you. I hope your remission lasts a long time and it continues to be trouble free. You obviously like to stay in control of your own healthcare and I applaud that – I am convinced that is half the battle. Cancer takes away more than physical well being; it takes away our sense of owning our bodies and our destinies. Having some level of control over health matters is important – you are lucky to have a responsive oncologist.
In the next week or two I will be publishing a new article titled “To wait or not to wait”. I think you will find it interesting. It has a case history that brings a sobering perspective and might be useful to patients “blessed” with bulky lymph nodes.
Chaya
Chaya,
Thank you for continuing this important work. You are a valuable link between the research and patient communities, and your continued efforts – especially in light your personal loss – are so very much appreciated. Thank you!
-Grant
Welcome back! Good luck on this venture in the new year! I certainly will support it.
Before I address Humax CD20, I would like to point out to Harley that more pertinent than his ALC is his CD4 count insofar as prophylaxis goes. Most researchers feel that it should exceed 200 before stopping prophylaxis against herpes viruses and PCP. He should discuss this with Dr. L.
I have been following the Humax story since you first brought it to my attention at the time of my initial diagnosis. The studies to date have been encouraging. My personal bias is that the trend toward earlier treatment of CLL (at least in those with poor prognostic indicators) needs to be explored with an eye toward better ‘control’ of the nasty clones involved.
Humax may be a useful part of that armamentarium, so studies utilizing it (perhaps in combination with other drugs) in such patients will prove interesting.
The first hurdle, of course, is to get FDA approval and expand it’s use so that an accurate picture of it’s true value can be obtained.
It will be interesting to see how FCH compares with FCR, for example, but the data will be a long time coming.
Unless I am mistaken, rituximab has never been officially sanctioned by the FDA for it’s use in CLL, though once a drug has been approved for any use, physicians may, at their discretion, use it for “non-approved” indications.
In the case of Humax, directly seeking approval for use in CLL appears to be the strategy chosen. This may lead to more rapid use in CLL once/if the FDA grants such approval.
It is really only when drugs are more widely used that we can learn of their true potentials and pitfalls.
In the case of Humax, it will have to compete with rituximab, which has a long track record (even if not approved officially for CLL) so the company will have to lobby hard for it’s use after it’s debut. My guess is that Humax will prove to be superior in most respects, but I am also sure that there will be patients who cannot tolerate it, while they can tolerate rituximab or some of the other anti-CD20 monoclonal antibodies currently under development.
Who can guess, in the end, other drugs (perhaps SMIPs) will displace all monoclonal antibodies. I only hope that i live long enough to see how it all turns out!
Chaya–
Although I haven’t relapsed yet (I am in my seventh year of remission) I don’t kid myself that I won’t. So I follow new treatments with interest and there is no better way to understand them than following your posts. Thank you for continuing this important work; I will certainly support it.
Cathie Nicholl
11qRick
I agree with your assessment of Humax-CD20’s chances of getting FDA approval are not a slam dunk. But who knows, with a new administration in place that says it wants input from general public, perhaps we will be able to do a bit of effective patient advocacy? Get in front of the FDA and let them hear our side of the story? Perhaps we can talk the Humax-CD20 folks to be a bit less pricey, and therefore more attractive to insurance companies? Any or all of it will require a cohesive patient community and spokesperson(s) with solid grassroots support.
Humax-CD20 is a better anti-CD20 monoclonal than Rituxan, I am willing to bet on that. It is not the proverbial CURE and there will be adverse effects that will surface as we learn more about it. There is no free lunch. But Humax-CD20 is better engineered for CLL patients with dim CD20 expression. I fully expect it will work better in FCH type combinations than the conventional FCR.
I agree the Genentech lead in the area is large and Rituxan is the present gold standard, but patients tend to vote with their feet – especially well informed patients like our membership. In this David versus Goliath contest my money is on David.
Chaya
Chaya,
Thanks for continuing this important work you do for us all. There are not words that can adequately express my Thanks.
What is the best way for those of us who are so busy to let the new administration know we advocate for Hu-Max 20 to receive FDA approval? Who is it we should contact?
I know the Leukemia and Lymphoma Society sends action updates via email that include a pre-written form letter that can be clicked and sent to legislaters re. bills that affect us.
If I knew who to write in Washington, I would do so either by form letter or a personal letter.
Chris Randolph
I’ll miss the alerts – as new/early stage CLL patient I tend to only think about it prior to appts and when a new alert comes out – still somewhat in denial but trying to get up to speed and take control.
I’m still struggling with all the jargon I need to learn just to catch up to “laymans” lingo.
Insisting on copies of all test results, plotting them, getting second opinion consult with Seattle Cancer Care Alliance specialist, and eagerly following CLL Topic’s. Glad not taking/needing treatments at this point, but worry that missing something that I should be doing other than trying to make each day count.
Thanks to Chaya and I will certainly make donations to help keep this info coming.
Ken
This is a comment from the other side of the pond Chaya – but like the above folks I am very glad you are back and have left a donation. Meanwhile, if you hear anything about NICE (the UK drug approval authority – National Institute for Clinical Excellence) before I do, it would be good to have it published for British CLL patients.
Thanks again
Lawrence (with one remission due to FCR under my belt, New Year 2009)
Lupner9 (Chris Randolph)
I will keep my ear to the ground on developments regarding Humax FDA approval process. When it is time to mount a write-in campaign, you can bet I will bring it to the attention of our membership.
I have been asked to appear in front of the FDA on previous occasions, by companies anxious to get our Good Housekeeping seal of approval. Up to now I have not felt the need to weigh in “officially”. But when Humax-CD20 comes up for review I think I need to make an exception and take a more proactive role. We need this drug on the open market, sooner the better.
At that time I will brainstorm with you guys on what it is we want to say to the FDA, what we want to accomplish and how best to do it. Back when I used to be senior licensing manager for ExxonMobil, my boss used to tell me I can sell sand to the Saudis, just so long as I could make it sound “scientific”. Let’s hope I have not lost my touch!
Chaya
I share your enthusiasm for Humax and respect your salesmanship skills.
When the time comes, not only would a grass roots mail (and email) campaign to the FDA and to the Obama administration be an excellent idea, but an unorthodox approach to consider is to see if you are able to recruit recognized CLL experts to lobby for it’s approval. This may be most effective if it comes from recognized experts who happen not to have any ties to Genmab (if there are any!).
Given your contacts throughout the CLL world, such a “calling in of favors” may not be so farfetched if the experts that you try to recruit truly believe in the merits of Humax.
Lobbying Genmab to moderate it’s price would most likely be worthwhile after the FDA grants approval for it’s use. Unlike the case with NICE, the FDA is less concerned with cost and more concerned with other issues.
We truly will learn a lot more about Humax after it is generally available for use outside of studies. Hopefully, most of what we learn will be positive! We must, however, be prepared for surprises on both sides of the aisle.
Let us know when to begin lobbying as individuals.
Rick
Chaya,
More strong work. Thank you. My check is in the mail. Please continue to remind those on your email list of the need for support.
One of many unanswered questions is why these ANTI CD 20 drugs work so poorly as mono therapy and yet add benefit without significantly increasing toxicity for just about all combos.
As you well know there is a line up of humanized CD 20 antibodies in various stages of research. I suspect that the next one to market may close the door to all those in line behind, superior or not.
Be well
Brian
Brian:
You ask a good question. A simplistic answer is that “naked” anti-CD20 monoclonals like Rituxan and Humax-CD20 do not have the killing punch of drugs like Bexxar, Zevalin (anti-CD20 drugs that carry with them a killing dose of radioactive material). Humax works better than Rituxan because it binds better to the CD20 marker, and once bound it does not come off as easily. The Velcro effect works better with Humax. This is important because the longer Humax sticks to the cancer cell without coming unglued, the better it mobilizes the body’s own complement system to kill the cancer cell.
While naked anti-CD20’s do not have much killing power on their own and need to depend on the body’s own immune system to give an assist, in combinations such as FCR, PCR, FR etc the chemotherapy components have more than enough power to kill. Rituxan and Humax do a terrific job of focusing that killing power. Any CLL cell festooned with anti-CD20 drug molecules becomes an obvious and immediate target, and therefore more effectively killed.
It is always a question of getting a good “therapeutic window”, where the cancer cells are killed in preference to ordinary (good) cells. Rituxan and Humax make the therapeutic window quite a bit broader: better killing efficiency when it comes to cancer cells, with less damage to healthy cells. If we were to try to get the same cancer cell killing efficiency with F +C as we get with FCR, we would have to use higher dosages of the F and C, and therefore see lots more adverse effects and toxicity. Rituxan and Humax allow us to get more bang for the buck, as it were.
Chaya, thanks for the new website and I look forward to keeping up with things again with the help of your website.
Humax has long been coming and I hope we can look forward to approval for it’s use soon. I am not sure how a Rituxan veteran will use Humax, but for newly diagnosed folks this might be a very good choice.
Welcome back Chaya, I am getting my reading glasses ready, I look forward to more.
Chaya, I am so glad that you are keeping on…and I hope my small donation helps. I have not the energy to search out all this material for myself and have depended heavily on you to do it for me. In addition to CLL, I have idiopathic pulmonary hypertension which has put a serious crimp in my lifestyle. My husband has also been diagnosed recently with a blood cancer (Waldenstraum); he is scheduled to begin chemo this next week and the oncologist made the comment that at least we will not be on the same treatment schedule. Meanwhile, we are both reading a lot and learning.
BJ
Thank you for continuing this work and please accept my condolence for your loss.
I have read the newsletter and once I figure out my Pay Pal I will begin to donate. Your website is the best that I have found and I look forward to your article on the watch and wait issue. I struggle with this and have conflicting messages from those who I see but am sure with more information I will have more confidence in my decision. Again thank you.
Gerald V
Chaya,
Congratulations to you and Radha on the new format. I can tell by the quality of your effort and by the thoughtfulness of the comments left by members that this is going to be an important forum for intelligent give-and-take on cutting edge issues in CLL. I am sure PC would be proud of you both.
I am glad to hear that you will continue and perhaps even expand your role as an advocate when it comes to such matters as getting FDA approval for useful drugs. While Genmab may have been smart in its approach (knock wood) to gaining approval of HuMax-CD 20, we all know that it will be of great use to more than just refractory patients.
I thought it was interesting to note that Genentech, which never received approval from the FDA for Rituxan in CLL, is now making an effort to get that approval. I assume this is part of the politics of the drug game and I hope that approval of Rituxan, if granted, would not lessen the chances of approval of HuMax.
Below is a press release on the subject, with reference to studies. I have pasted a pertinent quote below.
“Adding Rituxan to chemotherapy may be an additional option beyond chemotherapy alone for the more than 90,000 patients living with this incurable disease,” said Cecil Pickett, Ph.D., Biogen Idec’s president of Research and Development. “We plan to work with Genentech to submit the data from both CLL8 and REACH to the FDA for potential new indications for Rituxan in first- and second-line CLL.”
Just one more thing for people to know…Genmab (along with Glaxo-Smith-Kline) will likely use the trade name “Arzerra” for ofatumumab, rather than HuMax CD20.
Chaya:
Thanks for all you do to keep us informed and welcome back. I’m a 4yr 6mo survivor of smoldering SLL. I have very stable disease and so far I have done pretty well on Rituxan. Currently I am on watch and worry and I am hoping to stay in “good” territory until Humax gets FDA approval.This article was very informative.Any drug that is new that can give us more time is welcome.
Do you have any information on how close lumiliximab is to getting FDA approval? I have been searching the web but I cant find out much about where it is in the approval process.
Lumiliximab is an anti-CD23 monoclonal that may see use in CLL. We reviewed this drug earlier on CLL Topics website. My guess is that it will take a little while longer before it gets in front of the FDA. Last time I talked to someone in the company I heard 2010 mentioned as a possible target date.
Well before lumiliximab makes it on to the commercial scene, I hope we will see exciting new combination trials of Humax-CD20. Also needed is solid information on repeat use of Humax-CD20 as a single agent. For early stage and smoldering patients like never_saydie above, maintenance therapy with Humax-CD20 may give a second option when Rituxan stops working or they develop hypersensitivity to the “mouse-juice”.
Chaya:
Thanks for the update.
Chaya:
I’m a new member but have seen the site before. I’m a 12.5 yr. survivor of CLL. Treated once with Rituximab(to which I had a severe allergic reaction on the 5th infusion) and two cycles of Leukeran ;last one from Feb.08 to July 08. I’m about to start Fludarabine in a month or two. I guess this makes me refactory and I appreciate all the information and activism. I’ll send a donation soon and if there comes a time to lobby the FDA I’ll write letters. Keep up the good work. Sorry for your loss.
dentymic
Dear Chaya,
Thank you for all the information you give to the CLL comunity.
What do you think about the new trial in Europe that combinates Ofatumumab with Chlorambucil?
Lucienne:
I am not familiar with that one. Can you send me any details? I will look into it.
Chaya
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