The power and pitfalls of omics part 2: epigenomics, transcriptomics and ME/CFS
Simon McGrath concludes his blog about the remarkable Prof George Davey Smith's smart ideas for understanding diseases, which may soon be applied to ME/CFS.
Discuss the article on the Forums.

How the Big Pharma model is failing to bring effective drugs to market

Discussion in 'Other Health News and Research' started by Ecoclimber, Feb 12, 2015.

  1. Ecoclimber

    Ecoclimber Senior Member

    Messages:
    989
    Likes:
    2,440
    I'm posting this as I find this information and analysis on how difficult it is to bring effective drugs to market under the current pharmaceutical model by Prof. G spot-on. Permission to repost from Prof. G

    ClinicSpeak: lemon verbena biomarker study

    Why the nutriceutical have an uphill battle to see the light of day.

    "The biomarker study below shows that lemon verbena a dietary supplement reduces pro-inflammatory cytokines and markers in MSers compared to baseline. The author's imply that lemon verbena has anti-inflammatory effects that may help MS.

    This is really a proof-of-concept study and should lead to a full development programme to find the component in lemon verbena that is responsible for these effects. The active ingredient(s) could then be extracted or synthesised and tested in EAE or similar animal model of MS.

    Depending on how effective it is the investigators' may be able to define some novel IP (intellectual property) and patent the substance as a treatment for MS. The patent is essential if the investigators want to attract follow-on funding. The ideal route for the latter is outside of academia as a University spin-off company.

    The start-up money can then be used to do the necessary work on developing a formulation of the compound(s), establishing the pharmacokinetics and pharmacodynamics of the new drug, doing toxicology studies in two animal species (e.g. rats and dogs).

    By this stage the initial round of funding will be spent, 6-8 years of patent life will be gone and big Pharma will want phase 1 (first in man) and phase 2a (proof-of-concept) data before investing in the compound.

    The academics who have started this University spin-off will now have to attract a second round of funding, only this time it will need to be much larger. Phase 1 toxicology studies will need to be contracted out to a CRO (contract research organisation) at great expense.

    The phase 2a study will need to be designed; will it be a simple baseline-line vs. treatment period (similar to what we have done with INSPIRE) or parallel-arm placebo controlled frequent MRI study? Industry and serious investors will almost certainly want the latter. After the phase 1 & 2a studies another 3-4 years of patent life have expired and Big Pharma will be asking if there is really enough time left on the patent to do the necessary dose-finding 2b study and a full phase 3 programme to justify their investment.

    The business people will being say the anti-inflammatory market in MS is saturated and with small molecules off-patent, or due to come off patent, the market will be much less competitive.

    I predict that Pharma will say no thanks and the academics will be depressed that they have dedicated 15 years of their research careers to a project that has not be commercialised.

    Why am I so negative?

    It is simple, almost all new activity in the MS anti-inflammatory field is with repurposed or me-too drugs; i.e. a low-risk strategy. Very few companies are trying new anti-inflammatory drugs. This is why lemon verbena, or its active ingredient, has almost no chance of getting developed into an anti-inflammatory drug for MS using the standard pharma development approach."

    "I hope I have made the point that the current Big Pharma model is almost certainly missing many effective drugs. This is another reason why we need an alternative model."

    "The other option for MSers is to simply take lemon verbena without any real data to support it efficacy in MS. This is the usual route of nutriceuticals. Please note that nutriceuticals are not without problems.

    They may for example contain toxic substances or metabolites that in small doses are not a problem, but as soon as you start using them in pharmacological doses side effects appear. Nutriceuticals can also interact with other medications and cause problems. This is why we can't recommend them to our patients; evidence-based medicine is brutally blunt."

    By Gavin Giovannoni



    Mauriz et al. EFFECTS OF DIETARY SUPPLEMENTATION WITH LEMON VERBENA EXTRACTS ON SERUM INFLAMMATORY MARKERS OF MULTIPLE SCLEROSIS PATIENTS. Nutr Hosp. 2014;31(n02):764-77

    Introduction: Inflammation is one of the main contributory factors to the etiopathogenesis of MS. Dietary interventions with Lipia citriadora (lemon verbena) extracts have been proved to be effective in the prevention of inflammatory diseases.
    Objectives: The aim of this study is to evaluate the effect of lemon verbena supplementation in pro- and anti- inflammatory serum biomarkers of MSers with different clinical sub-types of MS.

    Methods: The effect of lemon verbena supplementation (10% w/w verbascoside) was evaluated in a randomized, double-blinded placebo-controlled study with 30 participants classified in relapsing-remitting (n=10), primary progressive (n=5) and secondary progressive (n=15) MS presentations. Serum cytokine and C reactive protein levels were assessed in intervention and control groups for each MS clinical subtype after 28 days of dietary supplementation.

    Results: Serum levels of C reactive protein and 8 cytokines/ inflammatory (IFN-G, IL-12, IL-23, IL-6, TNF, TGF, IL-4 and IL-10) markers were studied. Secondary progressive MS-supplemented MSers showed C reactive protein concentrations significantly lower compared to the placebo group (p<0.005). IFN-γ levels decreased for all MS-treated groups whereas IL-12 diminished levels were observed for relapsing-remitting type (p<0.05). Anti-inflammatory cytokine concentrations of IL-4 (difference 2.98 ± 2.99 pg/mL) and IL-10 (difference 1.78 ± 5.54 pg/mL) increased in secondary progressive MSers (p<0.05).

    Conclusion: The variation of several pro- and anti-inflammatory markers after supplementation suggests that lemon verbena extracts may affect cytokine profiles in multiple sclerosis. Further investigation on dietary components with antioxidant and anti-inflammatory properties may contribute to understand MS pathogenesis and ameliorate MS symptoms.
     
    PeterPositive and August59 like this.

See more popular forum discussions.

Share This Page