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Generic Imatinib Compared With Gleevec in CP-CML: Patient Outcomes Across 3 Countries

This worrying article comes at the very top of a Google News search today for imatinib.

Whilst we are assured in the UK by the NHS that the generics are biometrically equivalent to the branded version, this research casts doubt on this assurance.

The research here has its weakness in that only one undisclosed generic has been tested alongside Gleevec.

Now we all have to guess the name of the generic that is less effective than Gleevec. The researchers are potentially leaving us exposed to a generic that is only partially effective.

 

https://www.cancertherapyadvisor.com/ash-2018/chronic-leukemia-cml-imati...

My personal experience with generic imatinib is that it didn't give the consistent response I was experiencing with Gleevec.  After four and a half years with stable PCR scores on Gleevec my numbers started to rise.  Admittedly, I was on a low dose of 200mg per my preference and my doctor's consent.

If I remember correctly, my first generic was Sun and was then changed to Teva after a few months.

Here's my CML history:

My diagnosis started after I gave a routine blood donation to the Red Cross. The hematologist with the Red Cross notified me that my WBC was high and recommended I follow up with my general doctor.

09/2012   p210 transcript 118.7% IS @ Dx, t(9;22) translocation in all 20 of the metaphases examined, FISH - 93%, WBC 65.5, began Gleevec 400mg/day

12/2012   003.59% & bone marrow biopsy - no residual myeloproliferative features but detected 1/20 metaphases containing the Philadelphia chromosome, FISH - 5.5%

2013   000.914%, 000.434%, 000.412% 10/2013 000.360% & bone marrow biopsy - normal male karyotype with no evidence of a clonal cytogenetic abnormality

2014   000.174%, 000.088%, 000.064%

2015   000.049%, decrease to Gleevec 200mg/day, 000.035%, 000.061%, 000.028%

2016   000.041%, 000.039%, 000.025%

2017   000.029%, 000.039%, switched to generic imatinib 200mg/day, 000.070%, 000.088%

2018   000.233%! Tried switching to dasatinib 100mg/day - I want zero #4 back! Dasatinib at 100 and then 50 mg/day did not agree with me so I went back to generic imatinib 300mg/day. 000.013% The dasatinib did seem to be effective. It was probably just too high of a dose for me. Went back to a lowered dose of dasatinib, hopefully that will keep the side effects away and still be effective. 000.007% Dasatinib at 25 mg/day seems to working! 20mg/day Sprycel or 200mg/day imatinib 000.006% 11/19-21 three day fast

I am not at all sure about this study...

"Lastly, the current study may not have been designed to resolve all potentially confounding prognostic factors that could influence the final outcome and subsequently, the study conclusion. Specifically, the proportion of patients with CP-CML who had b2a2 transcripts was higher in the cohort receiving generic imatinib compared with that of patients who were given branded imatinib (41.4% vs 53.8%, respectively, P = .017) — and as the study authors point out in their abstract, higher levels of b2a2 transcripts in CML have been linked to “an inferior rate of molecular responses and survival in other studies."

Also, the study authors have stated that they have support from pharma companies. I have not checked which these are but it may be helpful to identify exactly who has funded this research. 

Meanwhile, I remain sceptical about (some) generic IM being inferior to the branded product.

Sandy

Hello Sandy.

I am also sceptical about this observational study and its results. Nonetheless, it does concern me that the researchers have suggested that possibly two generic versions of generic imatinib are substantially less effective than the branded version but they are not ready to declare the names of the lousy generics.

If the research is worthy of presentation (leading to the top-spot Google news story) then the researchers acting responsibly should clearly name the lousy generics so that patients can be moved to generics which are effective.

 

Hi Nimbus2, My last 2 BCR ABL tests show an increase which I am obviously concerned about .The Imatinib I was given the last few times is the INTRAPHARM one which is white I felt like I was just taking a paracetamol .I wonder if it could be this one that isn’t up to the job because my blood was 0.7% on a previous test and brand  .Denise.

It would be interesting to know how authorities assert quality. Are there independent inspectors? Regular testing of products? How does manufacturers ”earn” their licenses etc.

Hi Guys, I am new on this Forum, although I was diagnosed with CML many years ago (2010). I am from Poland, and we are also constantly being told here that Gleevec and generic imatinib are exactly the same, which is absolutely not true. While being on Gleevec, my PCR was stable, MMR with occasional total molecular response; since I was switched to generic Imatinib (various types) in 2013, my results have been getting worse and worse, when it comes e.g. to 0,2, I take 600 mg instead of 600, but then, either my bilirubine or creatynine levels increase, co I stop 600 mg after a month. Then, I have like 0.0059, but after coming back to 400 mg, the results get worse over a few months. This did not happened when I was taking Gleevec. I cannot come back to the original drug, it is not refunded any more, can you switch again to Glivec in the UK, when generic imatinib does not work on you? 

For drugs manufactured in UK the Medicines and Healthcare products Regulatory Agency (MHRA) have a process for ensuring drugs are made correctly, and carry out inspections. An outline is here. As I understand it any imported drugs need to have been through a similar regime in their country of origin.  

Thank you, Alastair.

I do agree with your statement. The problem is that there is a growing widespread perception among patients that the generic versions are not equivalent. The following article (just published), for instance, contains many inaccuracies:

https://www.nottinghampost.com/news/local-news/pensioner-leukaemia-left-...

The article referenced at the head of this thread serves to undermine confidence further because it adds credibility to the perception that some generic versions of imatinib are less effective than the original.  The researchers then refuse to declare to the medical community which manufacturers produce the less than satisfactory generic medicines.  The authors of the study document are in effect saying, "we know something that you don't".

I agree with Sandy - I am sceptical of the research presented not least because it doesn't look as if it is comparing apples with apples.  And the newspaper article cited does indeed contain so many inaccuracies that it is I think most unhelpful to patients: so much of it is just plain wrong.

A scientific theory for generic imatinib being less effective than the innovator, if approved by regulators such as the FDA, MHRA or EMA in accordance with long established and robust regulatory practice, has never been stated and I can't think of one.  And the data on side effect differences seems at best inconclusive (some show more side effects for generics, some less).

I can certainly see and understand why patients with a condition like CML would worry about switching from the original to a generic - but poorly designed studies and inaccurate media articles which purport to demonstrate a "difference" are unhelpful.  That being said, anyone who sees a real change in results and/or side effects should obviously go to their doctor and discuss switching back (or switching).  It is my understanding is that patients can switch back to the original in the UK.

Anyone taking Sandoz generic should have no concerns regardless, and it would also be interesting to see if this is one of the generics purported to be less effective and/or lead to increased side effects. Sandoz=Novartis=Glivec (in generic clothing). 

I have been taking 400mg Imatinib daily since 2005 and have been using generic versions since they became available. More recently I have been given a supply of Cipla 400mg capsules which look completely different from anything I have had before. viz. they are large, gelatine capsules. Everything up to now has been solid, brown or white tablets. It may be nothing to do with it, but since this change, I have been suffering from slightly upset stomach and headaches. I haven't had a BCR check since I started on these so I have no idea how effective they are. I just wondered if anyone else had a similar experience of this Cipla product. I am afraid that I have a rather large supply and it will be some time before I can try a different product unless I have some evidence that it is causing my problems.

Interestingly, my BCR ABL had been slowly increasing over the last three years and my doctor was threatening to change my medication. About 6 months ago I became interested in energy psychology and my last two checks have shown a marked reduction. My next check is not due for another month.

I asked a senior consultant at a public meeting whether the differences in side effects between Gleevec and the various generic equivalents is real or perceived.

He replied that the basic imatinib is pharmaceutically equivalent and that there is no doubt about that. He said that the possible differences lie in the binding agents which are used by the various manufacturers.

I asked him whether the patient will have similar effects if equivalent binding agents are used for medicines such as statins. He said it is not so much the binding agents that cause the difficulty but rather the combined reaction between the imatinib and the binding agents.

It was his opinion that patients who experience difficulties with one version of imatinib should be able to request a different version.

Hello RC Kirk
Are you talking dasatinib and imatinib in
alternative days.

No I've never alternated days with the drugs.  I did experiment with taking dasatinib one day a week and imatinib the others during the last three months and my recent PCR result was "weak positive".  The clinic changed to an out of state lab for the last test and the sample wasn't kept at a stable temperature so the result may be inaccurate.