Tuesday, 1 May 2018

My drug is better than your drug? Science or marketing?

Differences are being suggested between the interferons. 

Is this biology or marketing?
This study attempts to say pegylated interferon (plegridy) is better than interferon that is not pegylated (rebif) and uses clinical trial data from (2012-2017) to support this view. 

So is this a (subliminal) marketing exercise to say my drug is better than your drug? Ideally one would like to see plegridy against avonex, but we know that both of the drugs are worse than others....and NICE thinks that neither are cost effective.

Whilst I am sure this is a price reduction exercise, the question what is what would the biology be behind this?

Is there more effective interferon neutralization. We know that if you give beta interferon daily it may have efficacy advantage, but it also causes more neutralizing antibodies 

However, to do a superiority trial (to show one is better than the other in a head to head study) may take a lot of subjects in the trials. 

Can you use disparate trial data to get the answer?  I'm not so sure.  The people in the MS CARE study tended to have a short diagnosis to treatment range and had more lesions per year than PEGlayted interferon. If we compared relapse rate in interferon trials from the nineties to the noughties, there is a massive drop, therefore it is important to control studies adequately. However, once every two weeks has advantages over more frequent dosing.

Coyle PK, Shang S, Xiao Z, Dong Q, Castrillo-Viguera C. Matching-adjusted comparisons demonstrate better clinical outcomes with SC peginterferon beta-1a every two weeks than with SC interferon beta-1a three times per week. Mult Scler Relat Disord. 2018 Feb 18;22:134-138. doi: 10.1016/j.msard.2018.02.021. [Epub ahead of print]

BACKGROUND:Subcutaneous (SC) peginterferon beta-1a and SC interferon beta-1a (IFN beta-1a) have demonstrated efficacy in treating relapsing-remitting multiple sclerosis (RRMS) but have never been compared in direct head-to-head clinical trials, the gold-standard comparison. A well-balanced matching-adjusted comparison of patient data on SC peginterferon beta-1a, and aggregate data from published phase 3 clinical trials of SC IFN beta-1a, was conducted to provide additional information on the comparative efficacy of these two agents.
METHODS:Individual patient data from a study of SC peginterferon beta-1a 125 mcg every two weeks (ADVANCE) and pooled summary data from four published studies of SC IFN beta-1a 44 mcg three times per week (OPERA I and II, CARE-MS I and II) with similar populations were utilized. A comparison was conducted by weighting individual peginterferon beta-1a-treated patients, using estimated propensity of enrolling in SC IFN beta-1a treatment to match multiple key aggregate baseline characteristics of SC IFN beta-1a-treated patients. After matching, weighted annualized relapse rate (ARR), 24-week confirmed disability worsening (CDW), and clinical no evidence of disease activity (clinical-NEDA) were calculated and compared for peginterferon beta-1a and SC IFN beta-1a.
RESULTS: After matching, baseline characteristics were well balanced across treatment groups. At 2 years, ARR after matching was 0.256 for patients receiving peginterferon beta-1a (effective n = 376) and 0.335 for those receiving SC IFN beta-1a (n = 1218) (P = 0.0901). The percentage of patients who were relapse free over 2 years was significantly higher with peginterferon beta-1a than with SC IFN beta-1a (75.1% vs. 57.4% [after matching], P < 0.0001). The peginterferon beta-1a treatment group had a significantly lower proportion of patients with 24-week CDW compared with SC IFN beta-1a (after matching 6.5% vs. 13.2%; P = 0.0007). Clinical-NEDA occurred in a significantly higher proportion of patients treated with SC peginterferon beta-1a versus SC IFN beta-1a (74.1% vs. 48.1%; P < 0.0001).
CONCLUSIONS: This matching-adjusted comparison using data from four phase 3 trials with SC IFN beta-1a formulations demonstrated that patients with RRMS treated with SC peginterferon beta-1a 125 mcg every two weeks achieved better clinical outcomes than patients who received SC IFN beta-1a 44 mcg three times per week.

4 comments:

  1. Good question MD, I see there is a masters degree course in pharmaceutical marketing.

    ReplyDelete
    Replies
    1. Published by Biogen employees. Makes sense.

      Delete
  2. https://www.creativepegworks.com/PEGylation%20of%20Biopharmaceuticals%20-%20A%20Review%20of%20Chemistry%20and%20Noclinical%20Safety%20Information%20of%20Approved%20Drugs.pdf

    Nothing new here. Simply put, pegylation increases the half-life of the biomolecule and may reduce the immunogenicity toward the drug by reducing dose frequency. Pegylation of interferon for Hep C has been the standard for years. The question is: why wasn't beta-interferon pegylated for use in MS in the first place?

    ReplyDelete
  3. good to see where this was published

    ReplyDelete

Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.