Saturday, 26 August 2017

TeamG helps develop a licenced drug

The new eagle has landed, 

http://multiple-sclerosis-research.blogspot.com/2017/08/another-eagle-no-maven-has-landed.html

As you may know us academics are beaten with a stick to produce papers and to produce papers that have "Impact". This is some science babble invented to assess research groups by the UK Government

As a basic scientist it is very difficult to do something and see it all the way through to have "Impact" on Society, which is what they assess us on.

We provided the first science evidence why cannabis would work for MS and we also did work that helped pharma deal with the regulators but no "impact" for that one, because the idea was at a different university. It was eleven years between the discover and the impact

However, for neurologists it is much easier. 

Do a trial and that's the start of impact. In fact for us basic scientist it seems that our clinical colleges are dead good at ensuring we have no impact. 

The positive..em failed THC trial in progression
The positive.....can't be bothered to repeat and implement change...optic neuritis trial.

If you produce the data that can change clinical practice...this is clearly impact.

Thus licensing of Mavenclad is surely impact we have been involved with

Someone asked ProfG if we work for Merck, because we talk about cladribine. Is that surprising as ProfG was lead author on phase III work and was instrumental in developing the approach? Furthermore DrK has been using generic cladribine.

So first answer is no we do not work for Merck, however ProfG works with all companies with MS drugs and DrK also discloses such activities too. 

Did people care about this when movectro was gone and buried and we were the lone voice. 

I have not had a personal penny directly from Merck, not yet at least :-), nor one that I remember. I did give them a mouse colony (as I did to anyone asking for them) so they could do EAE work, but me or my University did not ask for or receive anything....although we did get offered free mice, if  they were surplus to requirements.    

So in 2010 ProfG was the lead author on the oral cladribine paper (CLARITY) study. I think we can claim a bit of involvement about something that surely has impact.  

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: 362:416-426.


Movectro was licensed in Russia and Australia but then CLARITY however, turned out to be the CALAMITY study as Merck had only done one trial and the regulators wanted two. 

They (Merck) dug their heels in and said "no more"  and removed cladribine from the market. They had lost the race with Novartis to be the first oral treatment 

It shows some money, over no money, is not good enough.......if you want lots of money. Have they not heard of Chuck Barris?

No...Neither had I until I went to Wiki

Impact down the toilet and a few smug people have a laugh.

But all was not lost, so in 2011, I hatched a cunning plan to bring back cladribine and get real impact by getting treatment for all. 


After a year long search to find a Neurologist, other than ProfG (too conflicted), outside the group, I eventually found one in Sir Jeremy who then spoke to DrK who rose to the challenge and I wasted a year. 

The Fox took shape.

Enter CLEAR-MS and the white knights drip feeding the World that cladribine was not dead and could be useful,  

For 5 years we kept the drug in the world's eye, until Merck woke up and decided they had made a mistake to bin their drug.

First we tackled the central bit of mud, stuck to the Movectro wall.



This was the cancer risk that had appeared in the trial and was the central feature that sunk the molecule.

We did a meta analysis and argued against the fluke phase III CLARITY trial result. This is less worse than the result with ocrelizumab in PPMS which the FDA approved

No support from Merck, just an honest belief that cladribine had merit as a treatment

As Manchester University/Brian Cox made the argument that he was responsible for an increase in physics students going to University to get an Impact Statement in REF2014  

Surely we can make the argument that Merck bringing back cladribine was all our doing...Impact Ref 2021. 

OK ProfG will be horrified by the trumpet-blowing, but he is in the air returning from holiday..hence being incognito on the blog in recent weeks, so can't take it down for a few hours:-)

Of course you, and actually I, will say that is b******s, to claim everything, but Manchester University did make that Impact statement for Prof Cox.... and was successful......Amaaaaaaaazing

So forgive my bit of horn blowing.

You can argue these actions have nothing to do with that. 

But what is the evidence?

Some may say it was the introduction of alemtuzumab that made the difference, because it was realised that an effective drug, with high side effects, could be approved.

So, still maybe we can claim some impact. 

Although it is clear the alemtuzumab was invented in Cambridge (Waldmann & Winter et al.), by people from Oxford, by Medics (Compston & Coles et al.) from Cambridge who ran the trials who no doubt claimed impact in their REF 2014. 

However, when it came to getting the drug licensed the Cambridge group went on holiday and could not be seen. Rev. Prof Coles was off on Sabbatical. ProfG was the guy who stepped up to the plate to help pharma do the important regulatory stuff that helped get alemtuzumab licensed, and licensed as first line treatment in Europe. 

So we can even claim we were the people that helped create the environment for the return of oral cladribine. Furthermore

DrK has been banging the Cladribine drum and Merck has heard it and this has also helped them revive their oral cladribine programme, maybe as the best way of stopping us developing cladribine for RRMS.
So back to Cladribine and when the EMA came knocking, ProfG was back there trying to do his bit to get oral cladribine, approved in Europe. It worked and oral cladribine now called Mavenclad is arriving in Europe.  Impact!

Will it crack the USA?
DrK did an independent study to indicate that the issues with cancer that was cause for concern by the FDA was no worse than for any other treatment and certainly not as bad as that found in the PPMS study of ocrelizumab. Ocrelizumab was approved for PPMS by the FDA. This study surely will give confidence for Merck to approach the FDA for a licence.

Furthermore, whilst Movectro was on holiday getting a make-over and realising that it is not possible for academics to licence MS drugs, DrK has been practicing what the General Medical Council preach...

Laura Waters“The General Medical Council is very clear that a clinician has a duty to make sure patients are informed of all treatment choices, whether they’re available on the NHS or not.” 

We  have given people with no choice an option and we used off-label cladribine. This has helped us determine how cladribine actually may work.

Will we tell Merck? Sure we will! 

If we find an issue will we tell the world, sure we will. 
That is transparency.

Furthermore,  could this now be the agent (generic) of choice in Low and Middle Income Countries as we have long been arguing. 

Off-label does not have to mean second best. It also gives people an option for people who can't swallow.

Maybe Merck will do a compassionate programme and give low and middle Income the drug for the cost of generic cladribine.
Now that would be impact as the average drug cost is higher than the annual income from many countries.

We can dream.

OK I will come clean, it is all Merck's Hard work that brought Mavenclad to be a reality.

So now I will have to shut up about cladribine.....Phew I here you say, in case you say I'm a Merck mouth piece...I'm not!

CoI: None DrK& ProfG most definitely

11 comments:

  1. MD you're back! Love the picture history :) Full credit for everything you've done and huge thanks :)
    Ps glad I've seen this before ProfG gets you to change it!

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  2. Thanks MD. It's good to get some context with passion. Keep the impacts coming!

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  3. Will this have a positiive impact on the MS-CHARIOT trial? This drug could be hope for the great unwashed who have progressive MS and misased the boat when they had RRMS.

    What ever you do do not stop talking about it and keep blowing that trumpet. I like the noise

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    1. Patrick, thank you for helping to keep momentum on #MS-Chariot (I’ve accepted by now that people prefer this spelling rather than #ChariotMS, so let’s keep yours!). Planning of the project is in full swing, and on target for submission in November. However, it needs extra cash. Those who reside over the money – we need £4 million in total, however cannot expect more than a third of that from the public purse (NIHR) – continue to have their earplugs firmly in place, or prefer listening to people who promise magic bullets for £100 million, albeit with uncertain timelines and no idea whether there will be success. Perhaps we're running into the same problem with charities as we did with industry: Once the likelihood of a tidal AND affordable change becomes realistic, hesitancy kicks in big time. Any explanation?

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    2. DrK thanks for all your hard work too! I'd at last taught myself to call it #ChariotMS as well ;) whatever we call it, is the idea to gain a licence for cladribine sc inj for progressive MS? Or to prove that it works but will still be off-label? How can we help? We need a plan ;-) why are MS charities not keen? Don't want to upset pharma?

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    3. Licensing is for industry. By the time we can - hopefully - confirm that cladribine slows progression in advanced MS, the oral preparation will arrive at the end of its patent life; wouldn't that be a beautiful co-incidence. Regarding plans for funding we're working with the charities and potential donors. Charities follow their own strategies and agendas, and what seems obvious and burning to you and me is for others just one among competing projects, and yes the impact of big pharma is not irrelevant.

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  4. Tumbs up, old man ;) and good work from you all.

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  5. You've done well, but Coles and Compston are still the kings. Lemtrada is more effective than your handful of smarties and was licensed c.3 years ago. Team G will be lauded when an effective neuroprotective reaches the market.

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  6. Thanks for your work!! Now let's hope the FDA approves as another option for treatment!

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  7. Thanks for your work!! Now let's hope the FDA approves as another option for treatment!

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  8. Hope it gets FDA approval! Thanks for your work.

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