Wednesday, 31 August 2011

Comment re laquinimod

Mr Giovannoni,

I don´t think it serious to refer to an analyst/equity researcher at an investment bank regarding laquinimods be or not to be. No offence, but should know that. Also, I think you are dismissing or press down the prospects of laquinimod wrongly.

NOT A PRETTY MS MARKET - DOG EAT DOG BEHAVIOUR Those investment bankers/analyst have loyalty to different MS-company´s (read: clients). For instance some investment bankers do big corporate and financial business with Novartis, Biogen or Merck and other promoters of specific MS-agents and have their loyalties to them and no other.

So their we have an explanation why this analyst and many others are NOT objective: they can simply discredit a competitors MS agent because the investment banker works for another company with another MS-agent. The investment banker business is a dirty business - it is a Dog Eat Dog business, as well as the Big Pharma business.

I know how the equity research and investment banker business works, because I worked 12 years in the city as an /Analyst Equity Researcher at an mayor investment bank That was before I caught the MS disease - I was diagnosed 8 years ago.

So, we know that the investment banker business is full of loyalties and ties to specific big pharma companys with MS-agents in their portfolio. So Mr Giovanni, referring to this analyst and investment banker Ori Hershkovitz is not so vice ... Belief me I have investment banker experience, and it is NOT a clean world … far from it. With all the ties and loyalties to different clients/companys.

An analyst working at an investment banker with Corporate finance departments, do not bite the hand that feeds them = their clients. That is just the way it works at an investment bank. Period!

And you should know, primary based on what I elaborated above, that I don´t use an analyst/Equity researcher at an investment bank as my MS-clinicians or adviser regarding the MS-disease and its course ...(!)

RELAPSES VERSUS DISABLITY AND LAQUINIMOD Also, I as a patient rather take a relaps once every third year or so, if I can stop the disablity progress. That is the main aim for me as a patient – not the relapses itself!

Also, laquinimod seems to have unique properties regarding the reduction of Brain Atrophy or tissue loss.

Also, the recently reported BRAVO study with laquinimod was imbalanced at baseline. The active laquinimod arm was in worse shape than the placebo arm, according to relevant MRI active disease markers at baseline.

At baseline, the percent of patients with gadolinium-enhanced lesions and the volume of T2 lesions at baseline were much lover in the placebo arm than than in laquinimod arm. Or another way to tell it: At baseline, the percent of patients with gadolinium-enhanced lesions and the volume of T2 lesions at baseline were much higher in the laquinimod arm than in placebo arm …

These metrics are, as you surely know, known to be important parameters of MS disease activity. It goes without saying, that laquinimod was behind placebo already at the start of the study, at baseline. I would be like having a hundred meters fast running at the Olympics, and let one person start 20 meters ahead of the other runners … Not fair play, to say the least …

And since you Mr. Giovanni, are so focused on MRI markers, you should acknowledge the reason for the pre-specified adjustment regarding the imbalance between laquinimod and placebo.

Also, if laquinimod would have had to positive above mentioned MRI markers at baseline for the MS-disease versus placebo, I would think it would be fair to say, that it would also be logic to adjust for such a imbalance ...(!) And if you acknowledge that, then logically you must see that it is intellectually honest and logic when the imbalance was the other way around, as with the Bravo study …

So all in all, of course it is logical to use the predefined adjustment, mentioned in the study protocol for the Bravo study, and of course, examined and granted by the FDA/EMA authorities.

Regardless how you angle things, at the end of the day it is to slow the progression of the disease which is priority number one for me as a patient: => stop/slow the disability.

Keep me as I am today as long as possible is my Top priority as a patient with MS. So slowing disablity is my prio number 1 and doing it in a safe manner.

Also, laquinimod has shown in human very promising elevation of BDNF, Brain-derived neurotrophic factor, treatment with laquinimod results in a significant increase in brain derived neurotrophic factor, a key protein responsible for the maintenance of mature neurons - up to 11 times elevation of BDNF in patients participating in phase IIb study with laquinimod. See references down below.

BRAIN ATROPHY – ITS IMPORTANCE FOR ME AS A MS PATIENT But the thing which makes me thrilled about laquinimod is that I think that we as patients has great hopes for laquinimod prospects for beeing an oral, safe agent with great NEUROPROTECTIVE properties.

Neuroprotective properties would explain the high score on disability reduction, measured accordingly to the established EDSS scale.

Also one must ask oneself this question:

At the severe MS-disease stage, SPMS, you don´t have any MRI markers regarding lesion, no relapses ... just a downhill degenerative destruction of the brain ... loss of brain volume or brain tissue loss.

And I belief I would make a real bet on, that laquinimod will be successful in this cruel segment of the MS-disease, SPMS, because of its neuroprotective properties.

So this focus on relapses is, according to me, as a 8 years diagnosed ms-patient, more or less a DEAD END. We must look after MS-agents with direct neuroprotective properties, which laquinimod definitely seems to have.

We must not be naive, the big pharma industry will never accept a competitor with a new agent with unique features. They will use the all the power they have to play down its importance. Not for the best of the patients, but for the best of their shareholders interest. MS is right now a 10 billion US dollar market ... So they have all reasons to be greedy.

So the Big Pharma business will play down this new agent, using spin-doctors, lobbyists etc to discredit a new unique agent. That is the way it works. The patient is just a revenue soldier for the industry - we as patients must remember that!!

A new agent in MS or another devastating disease, and its prospects, its not mainly to do with its power to treat the disease in a safe manner, it is to do with marketing and lobbyist network within the big Pharma industry against doctors and other opinion leaders.

MS - A DEGENERATIVE BRAIN DISEASE

Nevertheless, I personally view the MS-disease as a pure degenerative brain disease, where the reduction of relapses will not have any impact on this degenerative brain disease. It can´t have by definition.

I am not alone with that view, several key MS opinion leaders have also aired that view in science artichles and at conferences. So I am not alone ...

So having said the above, I have great faiths in laquinimods ability to reduce brain tissue loss or brain volume, formally called Brain Atrophy.

No matter what MS-clinicians would say to me, to remain the brain volume intact, with exception for normal brain Atrophy, which is related to ageing, I prefer to go on a future oral MS-agent like laquinimod, that will halting or slow the Brain Atrophy on me as an MS-patient, and thereby slowing the progression of this degenerative brain disease.

To be noted Laquinimod had very good scores on brain atrophy: In the Allegro study, laquinimod reached 33% reduction of brain Atrophy vs placebo. In the BRAVO study, laquinimod reached 27.5%, and this figure was statistically significant both before and after adjustment for imbalances at baseline between laquinimod and placebo.

Apart from the immunosupressive agent Gilenya, which in the FREEDOM study showed 30% recution in Brain Atrophy (only one study), the immunmodulator, non-immunsupressive agent laquinimod, is the only agent which has shown profound results in halting Brain Atrophy. Laquinimod has showned it in two pivotal studies, Allegro and Bravo. Gilenya only in the Freedom study.

But Gilenya has also safety problems, so it will not be my first choice. Laquinimod has none safety problem and a very benign profile, so it will therefore be my first choice, when if it will be approved by the drug authorities, FDA (US) and EMA (EU).

MY WAY IN FUTURE MS TREATMENTS …

If you add the score on disability for laquinimod, ut reached 36% reduction in the Allegro study. In the Bravo study it reached 33.5%. As mentioned earlier above, the Bravo study was adjusted for umbalance at baseline.

So for me, who has been on injections since diagnosis, Avonex, and now are offered to use the immunosupressive agent Gilenya, I will say no to gilenya and other agents and wait for the promising agent laquinimod to be approved and to be available on the market late 2012.

The story about a successful MS-agents for me as a patient, is to stop this degenerative brain disease and doing so in a safely manner.

I will be on treatment for the rest of my life, so safety is extremely important for me. And I think therefore laquinimod will be an unique new option of treatment for MS patients, who wants to fight the degenerative side of this disease.

Hope this comment not will be deleted by you Mr Giovanni, because my view on several issues regarding MS is not in line with your views. But then again, if everyone would always agree with each other, then we will have less development or progress. And we want progress, don´t we … :-)

All the best

PGC now living in Stockholm. Before my diagnosis in London.

Disclaimer: I have no ties or loyalties to the industry. I am only loyal to myself as an MS-patient.

REFERENCES:

BDNF and laquinimod: W. Brück ”Journal of the Neurological Sciences” JNS - 11705; No of Pages 7

BRAVO study: Audio webcast: http://phx.corporate-ir.net/phoenix.zhtml?p=irol-eventDetails&c=73925&eventID=4168607







1 comment:

  1. Mr Carlsson comment is in response to this earlier post
    http://multiple-sclerosis-research.blogspot.com/2011/08/laquinimod-fails-in-second-rrms-study.html

    ReplyDelete

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