"The number of PML cases is important because if the infection rate climbs too high, the drug's sales growth may drop. Regulators have said that they watch the cases, but have concluded that the benefits of the medicine to MS patients outweigh the risks.Biogen reports that as of Sept. 30, 2010, there are 55,100 patients using the drug around the world and that approximately 75,500 patients have used the drug since its launch. Of the 75 total cases of PML, 33 cases were in the United States, 38 cases were in the European Union, and 4 cases were in other areas.
The overall global PML rate is about 0.96 per 1,000 patients, a company spokeswoman said, which still falls within the 1-in-1,000 rate previously seen in clinical trials and implied on the drug's label. But the rate has been rising, and multiple Wall Street analysts raised concern about the trend on Wednesday as the MS market is becoming increasingly competitive."
"The most recent data update translates to a rate of 1.49 cases per 1,000 for patients on the drug for a year or longer, but rises to 1.97 per 1,000 for those on the drug for two years or longer.According to these growing numbers, the death rate of Tysabri/PML patients is at 20%. I wish that we knew the condition of the other 80% of PML patients. Unfortunately, I do not know the breakdown of the location of the 15 PML-related deaths.
Looked at another way, the rate is about 1.49 cases per 1,000 patients on the drug for between two and three years. The incidence is about 0.37 case per 1,000 patients in those using it for one to two years, and it is essentially nonexistent in patients using it for less than a year."
Source: Multiple Sclerosis Resource Centre and NASDAQ Copyright (c) 2010 Dow Jones & Company, Inc. (18/11/10)
Edited to Add:
The distribution of PML cases and number of deaths reported by Biogen and/or FDA is as follows:
Month reported; Total # PML cases; # in USA, # in Europe, Other; # Deaths
Nov 2010 - 75 total - 33; 38; 4 - 15 deaths
Oct 2010 - 70 total - 29; 37; 4 - 14 deaths
Sep 2010 - 68 total - 28; 36; 4 - 14 deaths
Aug 2010 - 63 total - 25, 34; 4 - 12 deaths
July 2010 - 58 total - 22; 32; 4 - 12 deaths
June 2010 - 55 total - 20; 32; 3 - 11 deaths
May 2010 - 49 total - 19; 27; 3 - 11 deaths
April 2010 - 46 total - ?; ?; ? - 11 deaths
Mar 2010 - 42 total - 15; 24; 3 - 9 deaths
Feb 2010 - 35 total - 11; 21; 3 - 8 deaths
Jan 2010 - 31 total - 10; 19; 2 - 8 deaths
Nov 2009 - 27 total - ?; ?; ? - 5 deaths
Sep 2009 - 24 total - 8; 16; 0 - 4 deaths
July 2009 - 11 total - 3; 8; 0 - 1 death
Here is the Morning Equity Briefing published on Davy Research website regarding the new PML cases and their impact on Tysabri usage.
Elan Corp (ELN US)
Monthly safety update on Tysabri
Jack Gorman
Closing Price: $5.55 Rating: Outperform 30/06/09
FACTS: The latest safety update on Tysabri was released last night (November 16th). Five new PML cases were confirmed during October and this brings the total to 75. Four of the cases were in the US, bringing the total there to 33. There have been 38 cases in the EU and four in the rest of the world. Fifteen of the 75 patients (20%) with PML have died.
ANALYSIS: The new cases have increased the overall incidence of PML in those patients exposed to Tysabri to 0.96 per 1,000 from 0.91 per 1,000. Observing the data by treatment epoch, the new cases look to be in patients with at least 25 infusions.
Distribution of PML patients by treatment epoch has stayed broadly consistent for some months now (note that all data are per 1,000 patients exposed). For 1-12 months, the rate remains at 0.01, indicating little or no PML. For 13-24 months, the rate is 0.37 compared to 0.38 previously. For 25-36 months, the incidence rate remains highest at 1.49, up from 1.44. The 37-48 month increased from 0.93 to 1.01 but remains lower than the 25-36 month cohort.
The data also outline, to 95% statistical confidence levels, what the estimated upper and lower bounds may reach for each of the treatment epochs. There is little change in the mix here and it continues to hover close to 2.0 for the longer durations.
DAVY VIEW: We would not expect that this monthly data will materially change physicians' or regulators’ views on Tysabri’s risk/benefit profile, as there looks to be no sharp increase in either the actual PML rate or the statistical upper bounds of incidence.
UPDATE: Biogen announces updated Tysabri/PML statistics. The total number of cases is now at 85 patients with the addition of 6 new cases reported in January 2011. The number of deaths holds at 16 patients. Of the total PML cases, 36 were in the U.S., 44 were in the European Union and five in other areas.
Hey Lisa,
ReplyDeleteAfter reading this, I feel like I've got a few things wrong, or rather the info I've found and have received from my doctor has been slightly skewed. I was under the assumption that the vast majority of PML cases came out of Europe, however what you've posted here shows the US and Europe almost neck and neck for cases.
You brought up a huge question in my mind, in regards to the well being of the patients who have developed PML but haven't died from it. Where are these people? What is happening to them? What is their quality of life like, and have any of the supposed treatments to try and stall the advent of PML worked? I feel a little jipped in terms of this info.
Coming off of Avonex, my doctor has advised Tysabri and it's just a waiting game right now with insurance approval and/or patient assistance. I made an appeal for Copaxone and that was shot down, so at this rate, it's looking like Tysabri.
Thanks for posting this, it's pushed me to keep further researching the issue...
Dana
Hi Dana,
ReplyDeleteI wish that we knew more about those other patients as well, but it doesn't seem like the company or medical folks are talking. Or if they are, I haven't read the information anywhere.
I went back and researched the numbers a bit, compiling the counts reported each month. You can find those numbers added in the post. (I wish I knew how to create a table within a post. It would be easier to read.)
At one point, it was true that the majority of PML cases were in Europe. Almost 2/3. But you can see that the balance has been shifting.
I'm almost more amazed that I haven't read any articles about the sharp increase in reported cases compared to one year ago.
Tysabri seems to be a powerful drug which is helping lots of folks. I hope that it helps you!!
I really am glad that I started using Rituxan (which also carries a PML risk). It works great for my RA and I'm hoping that it is working for the MS too. I haven't had a massive attack this year, so that's good.
Please keep us posted on how Tysabri works for you. I'd love to know. Good luck with it and do keep researching, keep digging for information.
HI Lisa-thank you for adding this list!
ReplyDeleteIt is frustrating for there to be this existing knowledge out there about "the other 80%" not being shared with the public. I have to say however, I'm not surprised that we're not seeing a whole lot of publication in regards to increasing cases of PML, especially as they pertain to the US.
I'm going to dig around in my school's library database as well, and see what I can find.
I'm glad to hear that Rituxan is working well for you so far, I hadn't thought much on the issue of other drugs also coming with a risk of PML. This was enlightening!
Thank you for the well wishes, I'll definitely be writing on mine and Jackie's blog about my Tysabri experience once all the ducks are in a row for me to get started on it!
Thanks again!
Thanks for this Lisa - even though the elephant in the room is of course how those who got PML but did not die are doing, still very helpful just to read some up to date info given the usual paucity out there.
ReplyDeleteHave just been at seminar today where there were plenty of Biogen rep's - aren't I wishing that I'd read your post before rather than after ... wouldn't I have been most keen to ask a few pointed questions of them if I'd read it prior!??
cheers
Is it true that according a policy link on myhealthcare.com , Medicare won't pay for Tysabri until a patient has taken other MS drugs?
ReplyDeletemyhealthcare.com/policies/medicare/Tysabri_Policy.pdf
Is it also true that the US VA hasn't approved Tysabri for veterans with Crohn's disease even though the FDA approved Tysabri for that indication back in Jan 2008?
Are MS patients taking natalizumab the sickest of those with MS?
Isn't Tysabri or natalizumab commonly given to MS patients who have FAILED other MS therapies like interferons & glatiramer acetate?
Haven't a good percentage of those same MS patients also taken chemotherapy or large doses of steroids like prednisolone?
Are you sure there is no problem with taking all these different drugs before getting Tysabri ?
Didn't Tysabri go through the same clinical trials as all the other MS drugs?
Does Tysabri seem to be getting different treatment by the FDA & VA government officials than older MS drugs?
Aren't the big pharmaceuticals dropping their smaller molecule drugs and moving to the newer monoclonal antibodies, because they are safer?
Doesn't the latest research show the increased reservoir of stem or progenitor cells (aka CD34+) mobilized by natalizumab aren't relevant in getting PML (PMID: 21078695) ?
If you're one of those MSers lucky enough to get natalizumab, shouldn't you at least act to help some others get up from their wheelchairs?
Do US combat spinal cord injured still get the old steroids?
Will 200 Saudis get natalizumab to see if it helps them "ambulate" in clinical trial NCT00871780 ?
And as for Made in USA Tysabri, is it true that the Department of Defense will FUND a small clinical trial of an OLD FRENCH drug called riluzole in NCT00876889 for spinal cord injury ?
Is it really true that 1 dose of natalizumab, the only FDA ok'd alpha4beta1 integrin blocking drug, moblizes an average 6 fold increase in the blood of MSers per PMID: 18195093?
Is it true that the US institution/guv'mint stopped that research on stem cell mobilization per PMCID: PMC2438208 ?
Is there any basis to believe that the US guv'mint doesn't want to support any preclinical research with alpha4beta1 integrin blocking drug, (like natalizumab?) that get crippled rats to support their weight with just 2 doses per PMID: 19038604 ?
If you're pleased with your natalizumab, will you please petition your US government to mandate an overseas clinical trial of natalizumab for US combat troops who may be spinal cord injured?
Don't they, of all disabled Americans, deserve at least the freedom to choose?
Dana, you're welcome! I really do hope that Tysabri does work well for you.
ReplyDeleteChe Koala, that would have been a great time to pick the brains of the Biogen reps. However, it is highly unlikely that real answers would have been given. :(
mypc2468, where to start? I don't allow spamming on my blog. I do allow differences of opinion, even if they come with agendas. Courteous decade is welcome.
However, what you have posted here does nothing to further the discussion. Perhaps if you were to post with a viewable profile, and fewer irrelevant and red-herring questions, then we could have a respectful talk.
I am undecided whether to allow your comment to remain on my blog since spinal cord injury is beyond it's scope. But I do thank you for deleting the 2nd comment on your own.
To answer ONE of your questions - NO, tysabri is not reserved for the sickest of MS patients. And I would venture to guess that the vast majority of tysabri patients have NOT taken other chemotherapy agents.