Is IMPACT coming our way-Merck back at the EMA

#MSResearch #MSBlog Cladribine is back on the table

One of the biggest drivers for improving/messing up the University System has been the Research Asssessment Excersises, now called the REF (Research Excellence Framework). These done every 5-7years are supposed to be a mechanism to increase the standard of academics within the university system. In some cases this means bullying and sacking, as a transfer system has been created, where the underperforming are moved out of research into teaching or are culled to be replaced by people with better REF-friendly outputs. This has bloated the number of professors, who demand promotion and better resources and salaries to move… at the same time killing our pensions as now there is not enough money in the system to pay for retiring professors:-(.

Each academic gets assessed and is given a value now rangine from dirt:-) to 4star. The number of 3 -4* gradings ( a marker of being internationally competitive) that the university gets dictates the slice of the decreasing amount money that government gives to the university. The way you are assesssed is based on your research output…which is are based on your papers. These then create a ranking for the Universities so Oxford and Cambridge come out top:-) Results & submissions : REF 2014

Historically the higher the impact factor of the paper the better, so a few papers in Multiple Sclerosis and Related Disorders Impact factor =1 verses is not going to cut it against New England Journal of Medicine. Impact factor = >40.

So the system is weighted in favour of clinical scientist and people doing Big Science.

However, to submit academics in the REF you had to have IMPACT statements (which are also graded), where research done at a university has created tangible benefit, and you had to have one of them for every 9-10 academics submitted.

If you want to have a look at these click here 

E.g. The TV-astronomer Brian Cox was the cited reason of why more people study physics at University….amazing.

A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis.Giovannoni G, Comi G, Cook S, Rammohan K, Rieckmann P, Soelberg Sørensen P, Vermersch P, Chang P, Hamlett A, Musch B, Greenberg SJ; CLARITY Study Group.N Engl J Med. 2010 Feb 4;362(5):416-26. 

Pakpoor J, Disanto G, Altmann DR, Pavitt S, Turner BP, Marta M, Juliusson G, Baker D, Chataway J, Schmierer K.No evidence for higher risk of cancer in patients with multiple sclerosis taking cladribine.Neurol Neuroimmunol Neuroinflamm. 2015 Oct 1;2(6):e158.

Does the development of a new MS drug represent impact surely one would think so…but I guess it is ranked lower than a new drug for Heart disease as the outreach is greater.

However it has to be approved by the EMA first and it has to be resubmitted

Today Merck has resubmitted oral cladribine back to the EMA

Merck Receives European Medicines Agency Acceptance for Review of Marketing Authorization Application for Cladribine Tablets

In 2011 the EMA view was  this (Click here)

Based on the CHMP review of data on quality, safety and efficacy, the CHMP re-examined its initial opinion and in its final opinion concluded by majority decision that the risk-benefit balance of Movectro in the treatment of highly active relapsing-remitting multiple sclerosis for the following adult patient groups:  

  • Patients with high disease activity, defined by two or more disabling relapses in the previous year, and one or more T1 gadolinium enhancing lesions or at least 9 T2 hyperintense lesions. 
  • Patients who despite treatment with disease modifying drugs for at least one year have persistent disease activity, defined by one or more relapses in the previous year while on therapy, and one or more T1 gadolinium enhancing lesions or at least 9 T2 hyperintense lesions. 

was unfavourable and that the application did not satisfy the criteria for authorisation and recommended the refusal of the granting of the conditional marketing authorisation.

The grounds for the decision are as follows: 

  • Serious safety concerns remain, in particular with regard to the higher number of malignancies observed in clinical trials. Therefore serious concerns remain on the long term safety.
  • Efficacy data in the restricted population with high disease activity or persistent disease activity despite treatment with disease modifying drugs are not robust enough to outweigh the safety concerns. Therefore the Risk-Benefit balance is not considered to be favourable. 
  • The lower end of dose efficacy curve has not been sufficiently evaluated. In view of the serious safety concerns, whether a lower dose with a better Risk-Benefit balance exists should have been established. 

The following criteria needed for granting a conditional marketing authorisation have not been met: 

  • The Risk-Benefit balance of the product is positive;
  • Fulfilment of unmet medical need has not been sufficiently demonstrated; 
  • Consequently, the benefit to public health of the immediate availability on the market of the medicinal product concerned does not outweigh the risks inherent in the fact that additional data are still required.

What has changed since then

More trials Done but not completed
                              Register after licenced Use of oral cladribine
                              (More efficacy and importantly safety data)
Lower Dose Study: Not Done

More Dangerous drugs approved: Alemtuzumab 
                                                           More adverse reactions &
                                                           More Lymphopenia

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