Wednesday, 1 March 2017

#PoliticalSpeak: become an activist and sign our petition

Help us get #EliLilly to disclose the results of their #Tabalumab trial. #PoliticalSpeak #MSBlog

As you are aware we and others hypothesise that MS is caused by a subset of abnormal B-cells that reside in the memory pool. We have developed this hypothesis over many years and it supports the EBV theory of MS. Learning about how MS disease-modifying drugs effects MS is important in supporting, or refuting, our hypothesis. We are particularly interested in the results of the trial below of Tabalumab (LY 2127399) a drug  that targets B-cells. Based on other data, and our hypothesis, we predict that this drug will make MS worse, by expanding the particular subset of memory B-cells we are interested in. Predicting worsening of disease is one thing, actually knowing the result of the trial is another thing. MouseDoctor and I have both asked Eli Lilly for the data and they have so far resisted. Is it appropriate for Eli Lilly to keep this data undisclosed?

We note and thank you for you support.  We now need to formalise this. You can help us by signing the petition below? The trial involved many sites across the world and if you happen to be a trial participant we would appreciate you telling us. Who knows it may help nudge the Eli Lilly executives to disclose the trial results. Thank you. 







Multiple Subcutaneous Doses of LY2127399, an Anti-BAFF Human Antibody, in Subjects With Relapsing-Remitting Multiple Sclerosis

Locations


United States
  1. Phoenix, Arizona, United States, 85013
  2. Tucson, Arizona, United States, 85741
  3. Fullerton, California, United States, 92835
  4. Denver, Colorado, United States, 80220
  5. Naples, Florida, United States, 34102
  6. Plantation, Florida, United States, 33324
  7. Sarasota, Florida, United States, 34239
  8. Northbrook, Illinois, United States, 60062
  9. Indianapolis, Indiana, United States, 46202
  10. Kansas City, Kansas, United States, 66160
  11. Lexington, Kentucky, United States, 40513
  12. Biddeford, Maine, United States, 04005
  13. Farmington Hills, Michigan, United States, 48334
  14. Toms River, New Jersey, United States, 08755
  15. Schenectady, New York, United States, 12308
  16. Charlotte, North Carolina, United States, 28207
  17. Raleigh, North Carolina, United States, 27607
  18. Akron, Ohio, United States, 44320
  19. Green, Ohio, United States, 44685
  20. Greensburg, Pennsylvania, United States, 15601
  21. Greenville, South Carolina, United States, 29615
  22. Franklin, Tennessee, United States, 37064
  23. Memphis, Tennessee, United States, 38120
  24. Lubbock, Texas, United States, 79410
  25. Round Rock, Texas, United States, 78681
  26. Newport News, Virginia, United States, 23601
  27. Roanoke, Virginia, United States, 24018
Bulgaria
  1. Sofia, Bulgaria, 1407
Czech Republic
  1. Brno, Czech Republic, 62500
  2. Pardubice, Czech Republic, 500 05
  3. Prague, Czech Republic, 140 59
France
  1. Caen, France, 14033
  2. Montpellier, France, 34295
  3. Nimes, France, 30900
  4. Strasbourg, France, 67091
Germany
  1. Berlin, Germany, 13156
  2. Ulm, Germany, 89075
Hungary
  1. Budapest, Hungary, 1095
  2. Gyor, Hungary, 9023
  3. Gyula, Hungary, 5700
Israel
  1. Tel Hashomer, Israel, 52621
Poland
  1. Gdansk, Poland, 80-952
  2. Gliwice, Poland, 44-100
  3. Grodzisk Mazowiecki, Poland, 05-825
  4. Krakow-Nowa Huta, Poland, PL-31-826
  5. Lodz, Poland, 90-549
  6. Lublin, Poland, 20-090
Romania
  1. Targu Mures, Romania, 540136
Russian Federation
  1. Kazan, Russian Federation, 4420029
  2. Kemerovo, Russian Federation, 650066
  3. Moscow, Russian Federation, 119435
Serbia
  1. Belgrade, Serbia, 11000
  2. Nis, Serbia, 18000
Slovakia
  1. Bratislava, Slovakia, 833 05
  2. Kosice, Slovakia, 04011
  3. Spisska Nova Ves, Slovakia, 05201
  4. Zilina, Slovakia, 01001
Ukraine
  1. Dnepropetrovsk, Ukraine, 49027
  2. Donetsk, Ukraine, 83037
  3. Ivano-Frankivsk, Ukraine, 76008
  4. Kharkiv, Ukraine, 61000
  5. Vinnytsya, Ukraine, 21005Zaporizhzhya, Ukraine, 69057

Primary Outcome Measures:
  • Reduction in cumulative total gadolinium (Gd)-enhancing MRI lesions. [Time Frame: Baseline, 24 weeks ]

Secondary Outcome Measures:
  • Total number of Gd-enhancing MRI lesions. [ Time Frame: 4, 8, 12, 16, 20, 24, 30, 36, 42, and 48 weeks ]
  • Total number of new or newly enlarging T2-weighted MRI lesions. [ Time Frame: 4, 8, 12, 16, 20, 24, 30, 36, 42, and 48 weeks ]
  • Time to first relapse. [ Time Frame: Weeks 24, 48 and period in between. ]
  • Proportion of relapse-free subjects. [ Time Frame: Weeks 24, 48 and period in between. ]
  • Proportion of subjects with anti-LY2127399 antibodies. [ Time Frame: 24, 48, and 72 weeks ]
  • Pharmacodynamics of selected peripheral B cell subsets. [ Time Frame: Week 72 ]
  • Serum pharmacokinetics (AUC). [ Time Frame: 42 weeks ]
  • Expanded Disability Status Scale (EDSS). [ Time Frame: 12, 24, and 48 weeks ]
  • Multiple Sclerosis Functional Composite Scale (MSFC). [ Time Frame: 12, 24, and 48 weeks ]
  • Visual Analog Scale (VAS) of Wellbeing. [ Time Frame: 12, 24, and 48 weeks ]
  • Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). [ Time Frame: 12, 24, and 48 weeks ]
  • 16-Item Quick Inventory for Depressive Symptomatology Self Report (QIDS-SR16). [ Time Frame: 12, 24, and 48 weeks ]
  • Total number of new Gd-enhancing MRI lesions. [ Time Frame: 4, 8, 12, 16, 20, 24, 30, 36, 42, and 48 weeks ]
  • Total volume of T2-weighted MRI lesions. [ Time Frame: 4, 8, 12, 16, 20, 24, 30, 36, 42, and 48 weeks ]
  • Annualized relapse rate. [ Time Frame: Weeks 24 and 48. ]

Estimated Enrollment: 245
  • Study Start Date: April 2009
  • Study Completion Date: June 2012
  • Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)

Eligibility
  • Ages Eligible for Study: 18 Years to 64 Years (Adult)
  • Sexes Eligible for Study: All

Inclusion Criteria:
  • 18 through 64 years of age diagnosed with relapsing-remitting multiple sclerosis (RRMS), who can walk without aid or rest for at least 200 meters (approximately 1/10 of a mile).
  • Women who can become pregnant must use birth control.

Exclusion Criteria:
  • Have had a live vaccination within 12 weeks before randomization, or intend to have a live vaccination during the course of the study.
  • Have had had recent surgery or are scheduled to have surgery during the study.
  • Are immunocompromised or have evidence of active infection (such as hepatitis, tuberculosis or, human immunodeficiency virus [HIV]).
  • Have been on certain drugs that are being studied for RRMS or have recently received prescription drugs to treat RRMS.
  • Have had a recent serious infection.
  • Have serious or uncontrolled illnesses other than RRMS.
  • Have clinically significant blood test values.
  • Have multiple or severe drug allergies.
  • Have contraindications for magnetic resonance imaging (MRI; "scanning") or claustrophobia (fear of an enclosed space) that cannot be managed.

ClinicalTrials.gov identifier: NCT00882999

Responsible Party

Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00882999 History of Changes
Other Study ID Numbers: 12778 H9B-MC-BCDJ
Study First Received: April 16, 2009
Last Updated: June 22, 2012



The Hypothesis

Baker et al. Memory B Cells are Major Targets for Effective Immunotherapy in Relapsing Multiple Sclerosis. EBioMedicine. 2017 Jan 31. pii: S2352-3964(17)30045-2.

Although multiple sclerosis (MS) is considered to be a CD4, Th17-mediated autoimmune disease, supportive evidence is perhaps circumstantial, often based on animal studies, and is questioned by the perceived failure of CD4-depleting antibodies to control relapsing MS. Therefore, it was interestingly to find that current MS-treatments, believed to act via T cell inhibition, including: beta-interferons, glatiramer acetate, cytostatic agents, dimethyl fumarate, fingolimod, cladribine, daclizumab, rituximab/ocrelizumab physically, or functionally in the case of natalizumab, also depleted CD19+, CD27+ memory B cells. This depletion was substantial and long-term following CD52 and CD20-depletion, and both also induced long-term inhibition of MS with few treatment cycles, indicating induction-therapy activity. Importantly, memory B cells were augmented by B cell activating factor (atacicept) and tumor necrosis factor (infliximab) blockade that are known to worsen MS. This creates a unifying concept centered on memory B cells that is consistent with therapeutic, histopathological and etiological aspects of MS.

13 comments:

  1. You could alwasys do your own petition and send it to us.

    ReplyDelete
  2. Please note this is about the science and not taking a shot at Pharma. The experiment has been done and if it was negative, or worse made MS worse, we need to know that so as not to put pwMS at risk in the future and to save money and time in not repeating experiments unnecessarily.

    Eli Lilly may have learnt a lot about MS from this study and are using the information to design their next drug. If that is the case we are unlikely to get the data. If not the the community needs to know.

    ReplyDelete
    Replies
    1. I feel let-down more than anything and really feel like Lilly are frustrating MS research.

      Delete
  3. Thank you for posting this survey. Completed. Will try and encourage family, friends and other pwMS to do likewise. Great to see you've already heard from some trial participants, they must be especially keen to know what happened.

    ReplyDelete
  4. Prof G, it is in fact unethical to repeat failed experiments in patients and how can repeat blunders be avoided if the results of failed studies are not published? We are not taking a shot at anybody, but there is a certain collective responsibility in medical science.

    ReplyDelete
    Replies
    1. This is a good example why pharma should be taken to task and the rules changed. In the age of information this data should not be allowed not to surface properly Importantly it should not be allowed not to surface within a rasonable time frame.. People have risked their lifes to create the information. For it to languish in a bottom drawer is terrible
      A negative result can be as informative as a positive result, which is why we do not pressure people in the lab to get a certain answer.

      That is the nature of science

      Pharma will say it costs money to do this but the data is already analyed they know if it works or not, so publish it

      Give the data to an academic and they will publish it for free. Indeed we are paying open access costs. This way pharma dont have to pay a new car for some medical publisher to write the paper.

      Down side is then pharma can't control what is said ..

      Would you let me loose with clinical trial data?
      Current pharma is saying No!

      Delete
    2. Maybe they can change their mind. But be veeeery nice :-)))), because you would like more data than they are required to make available :-)

      Delete
    3. Doubt it but lets see.

      However you have hit a nail on the head..the companies have more data from trials than they publish...we need to know more.

      We have got a number of requests in...hope we dont have to name and shame them too:-(

      I can't wait until ocrelizuimab gets approved, this can be a test case as they have to release the data if they are to live up to their promises.Will they?

      Delete
  5. Somebody on shift.ms mentioned alltrials.net (it looks like people are getting fairly furious about unpublished trial results). At least some people. Maybe EliLilly could turn it into a nice and positive gesture for the companyand declare that they are going to do all they can for their customers (oops! patients) from now on and make all results available? ;-)

    ReplyDelete
    Replies
    1. Thanks anon 6.37 have checked out alltrials.net and signed up.

      Delete
  6. Just watched this video from clinicaltrials.net. https://www.youtube.com/watch?v=Kto5vuiS5rA

    Ben Goldacre (featured in the video) has been battling in that field for decades - and still the pharma side is pretending medicine is like selling sofa cushions and they can do just as they please.

    ReplyDelete

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