I think this is a debate that can run and run and will only be concluded once the relevant authority grants or does not grant approval for this treatment. This decision will have to be made on the basis of completed trials and the success or otherwise of them. If the treatment does turn out to be as good as the press reports, one could imagine one of the larger drugs companies making a bid for Daval or purchasing the rights to Aimspro.
I would like to find out more about Daval International and in particular who is financing Aimspro. I understood that small investors had provided the finance - probably on the basis of the press reports.
Let us all hope that Aimspro is as effective as we have been led to believe.
The question of the granting of a license becomes academic if Daval has been bled to death in the interim. An un-named complainant raised an undisclosed complaint against Daval last year to the DTI who, in the process of their investigations, found nothing untoward other than some comparatively minor discrepancies in operating procedure which they advised the company to change. No charges were brought, no action was taken but Daval had to spend precious resources fighting their corner and lost the opportunity to raise further investment (their only current source of income) during this 3 month period. An ongoing campaign of obstruction and legal sniping is exactly the kind of action that makes sense if you want to kill off a small company, or their product.
All investor information is in the public domain at the companies House website. Investors, both large and small, were the source of operating revenue after David Shotton had almost single-handedly funded the company from day 1. Some patients have indeed bought shares - they may do very well in the end from it - but I would wager the large majority had an equally strong committment to helping the company which had effectively done so much for them - and at no charge!
I would also like to point out in answer to questions raised on other discussion sites - that at no time have Daval either deliberatly sought investment from these informed consent patients not have they ever even alluded to the idea that investment could possibly bring about a place on this list. Apart from having been a patient for 4 years, I have personally attended 90% of the company's investment meetings so I should know.
I know I keep harping on about it but I will repeat my motivation for defending/supporting Daval/Aimspro... this is an extraordinary treatment that deserves to be given nothing less than a very fair shot and only judged on its results. Industrial "warfare", political manouevring and bureaucratic dithering do not have a place in this process, yet they exist. They have the potential to delay or even destroy Aimspro and it is therefore quite understandable and certainly morally correct for some of us to be prepared to voice our opposition to the detractors, especially when they have nothing other than unsubstantiated evidence themselves.
The "game" of pharmaceutical chess and the commercial pressures are only too real and tend to be ignored, whilst the principled argue and debate about what is the correct approach and how, and on what, judgements should be made. Principled debate is all very well but not if you forget that there are big players out there who make up their own rules and couldn't give a damn about being correct - just more profitable!
The following had been sent for posting on the Proventus website last week but, owing to email rather than phone communication, I was unaware that our web designer was out of the country for 2w and therefore out of the loop. As the lack of fresh content on the site has caused disquiet in some quarters, I have opted not only to try an find another work-around but also to put this posting directly onto the forum. It may not be the full outcome of the MHRA's discussions with Daval as that is still to be pronounced upon by the MHRA but it is at least of relevance. The posting is to be linked from the news page and reads as follows: -
Abstract from the Optic Neuritis trial paper
(with additional comments in italics).
The evaluation of a novel ‘goat serum’ therapy (Aimspro) in multiple sclerosis
Background: Anecdotal reports suggest dramatic immediate clinical improvement when HIV / B3 cell supernatant inoculated goat serum (Aimspro) is given to patients with Multiple Sclerosis (MS).
Objectives: This is the first randomized, double-blind, placebo-controlled study of this treatment and was designed to explore the effect of short-term administration of Aimspro in MS patients with fixed optic nerve dysfunction.
Methods: Twelve subjects (mean age 40.4 years, range 27-50, median EDSS 4, 7 females and 5 males) with clinically definite MS (6 RR, 5 SP and 1 PP) and a history of optic neuritis more than three months prior to the study, with residual visual impairment were recruited. Objective neurophysiological, functional magnetic resonance imaging and visual field assessments were performed and results compared between the two groups (Aimspro versus placebo). The study was powered to detect a 0.5% change in the fMRI primary outcome, with an estimated standard deviation of 0.4%, allowing for 10% subject dropout.
Results: Both Aimspro and placebo were well tolerated and there were no serious adverse events. Treatment with Aimspro showed no significant benefit in the primary or secondary outcomes: visual evoked potential amplitude or latency, or the amplitude of the BOLD response in the fMRI experiments. There was a significant treatment effect in the tertiary outcome of visual field function (p=0.02).
Conclusions: This study was exploratory and only measured immediate change after three treatment doses. The major visual deficit in most patients was peripheral and the only outcome that assessed this area significantly improved with treatment. These results are encouraging and support the need for further clinical trials.
J. A. Palace, G. Burke, A. Cavey, P.M. Matthews
University Dept. of Clinical Neurology
Oxford. OX2 6HE, UK
(Funding for the study was provided by Daval International Ltd., who own the patent on Amispro. However, the study was designed independently by the investigators, who were responsible for the conduct, analysis and interpretation of the results.)
Essentially there were 3 outcome measures in the trial but these were not necessarily in order of importance, just convention. Certainly the primary and secondary ones (VEP & fBOLD measurements) showed no change in response to treatment and the tertiary one (visual fields, which was "the major visual deficit" in the test subjects) was clearly improved but without being "dramatic" or "outstanding". These were objective and scientifically measurable features - what wasn't measured or reported on were the subjective results as perceived by the test subjects themselves.
It says in the discussion of the results towards the end of the full paper,
"For these reasons, only a dramatic improvement in visual function would be expected to show a significant treatment effect in these parameters."
- VEP & BOLD (ie. you can still have definite subjective improvement without a correspondingly good objective measurement) and,
"Furthermore, since fewer fibres originate from the periphery, reducing damage to just a few fibres may result in a detectable improvement in peripheral visual function."
- (ie. beneficial effects in a lower number of fibres - and therefore harder to measure - can still give an important change for the better to the patient).
In other words there are very good reasons why the correlation between the first two outcome measures and the subjective benefits in sight to the test subjects is not direct and linear. In plain english this means that any improvement that a patient may notice is not automatically reflected in what the scientists can measure. Vice-versa, a "no improvement" outcome measurement can still be experienced as a very worthwhile improvement to the patient. The choice of outcome measures doesn't seem to have been especially intuitive in hindsight but then again these have to be chosen in the design stage of the trial and not once the effects have been seen.
Other comments on these results posted elsewhere on the web seem to focus on the key statement of "no improvement in the primary and secondary outcome measures" rather than on what was experienced by the subjects, who apparently all reported a subjective improvement in vision on Aimspro. It would seem, at least in some regards, better to have a treatment that enabled a patient to "see" an improvement (irrespective of what the scientists' measurements said) than one which showed results in the laboratory but left the patient unaware of any change in their sight.
Proventus accepts the vital role of clinical research in assessing Aimspro but it should not be forgotten that patients are the ultimate beneficiaries of any success and not scientific instruments. Nor should an understanding of any research results be based on phrases taken from articles quite out of context - it must be made in the round and with a reasonably full comprehension.
- Finally, a comment from one of Proventus' members on the informed consent list...
"Furthermore, this trial was carried out over a very short time span (3w) and, from our own personal experience, I feel there was insufficient time to evaluate the true potential of the treatment, i.e. although my wife had an almost instant recovery with respect to the squint in her left eye, it was only after eight weeks of treatment that the visual blurring had cleared and it was several months more before she could tolerate bright sunlight."
The reason it has not been approved, is because it has not succeeded in double blind trialsarql28 wrote:i HAVE NO IDEA WHY THEIR HAVING PROBLEMS WITH GET PASSED PHASE 2 EXCEPT THE DRUG COMPANYS MONEY MONEY
As with most if not all MS meds, specific ones work for one group, and fail for others. This medication does not work as well as it did for you, for everybody. I personally tried it, and got little (*possibly* a very small reduction in tingling) if any benefit from it.arql28 wrote:THIS DRUG WOULD TAKE OUT EVERY DRUG FOR MS ON THE MARKET AND THIER WOULD B NONE LEFT EXCEPT THIS ONE.THAT'S HOW GOOD THIS DRUG IS,
THER UNITED STATES/FDA WILL NOT EVEN LET THIS DRUG OUT WHAT SO EVER AND WONT EVEN LET THE UK TRY OR EVEN GET PASSED 1 PHASE. I WOULD LOVE FOR SOME 1 TO EXPLAIN THAT ONE!!!!!!!!!!!!!!!arql28 wrote:I really don"t understand why the goe rnment has such a problem with this Drug and SF1019.I been on them and a friend also.I have tried most drugs on the market and nothing compares 2 this by far.T heir is no limit on the amount of money i would spend 2 get this drug again.I guess when you go from not being able to jog,run,hands shaking nonstop,being sick and extreme pain,who woul'nt .I would say it took 70percent of that away and made it managable t o live.i now am confined 2 my condo and don't leave my couch to where it's very hard to even get stuff around the house done.I had no side effects on these drugs what so ever as well as my friend.I don't care what any study sdays i know this works and i believe it should be my own choice if i want to take it even if it did have risks.This countTRY/FDA is a jk and it's all about money which would wipe out billions in all the other drugs cause they wouldnt stand a chANCE AGAINST IT.I do feel blessed 2 have been able 2 been on it for a short term even though it was a tease it still gives me some hope their's drugs that stop the symptoms.WE ALL NEED 2 GET 2GETHER AND DO SOME THING TO GET THIS DRUG OUT ON THE MARKET
http://www.davalinternational.com/named ... ramme.html
And as for the FDA not allowing access:
http://www.davalinternational.com/regul ... tatus.html
It was interesting to read all the Orphan Drug designation provided by the TGA (basically Australia's equivalent to the FDA)AIMSPRO was awarded an Orphan Drug Designation by the Food & Drugs Administration (FDA) in the United States for the treatment of ALS, with effect from 28th October 2009. Following submission of additional supporting data, a further extension was granted recently by the US FDA for 12 months.
So, as far as I can tell, as it was for myself a few years ago, if you can find a compassionate GP, the drug is available on the market for purchased. But it ain't cheap.
And anyone who thinks its all puppy dogs and fairies, should read the following for perspective:
http://www.thisisms.com/forum/aimspro-f ... c3462.html
Goat Serum Extract Stops Progressive MS
By John Gever, Deputy Managing Editor, MedPage Today
Published: May 31, 2013
Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania
Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
In this retrospective, uncontrolled, chart-based review, British patients who received a non-approved treatment for MS demonstrated some subjective improvement.
Be aware that AIMSPRO has not been approved for marketing anywhere, the one unpublished randomized trial appears to be negative, and the lead author of this study owns stock in the company that produces AIMSPRO.
ORLANDO -- A controversial product derived from goat blood appeared to benefit patients with secondary progressive multiple sclerosis in an open-label study, researchers said here.
Among 140 British patients receiving up to 3 years of treatment with the proprietary extract, called AIMSPRO, in clinical practice, 100 showed improvement in at least two separate areas of MS-related symptomatology, according to Christopher E.G. Moore, MSc, MBBS, of Queen Alexandra Hospital in Portsmouth, England.
Although Moore and colleagues did not calculate Expanded Disability Status Score (EDSS) values for patients in the study, the clinician-estimated improvements in two or more symptom areas ought to translate to decreases of at least 0.5 points in EDSS scores, they argued.
The study results were presented at the joint meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
AIMSPRO includes a cocktail of immunoglobulins targeting human proteins, including proinflammatory human leukocyte antigens, according to the product's developer, Daval International Ltd. of Eastbourne, England. It also upregulates anti-inflammatory cytokine, the firm said. The drug is administered by subcutaneous injection in doses of 4.5 mg at individually determined intervals, most often twice weekly.
It was originally developed as a potential anti-HIV therapy, but Daval later shifted emphasis to other conditions including MS as well as systemic sclerosis and amyotrophic lateral sclerosis. Although AIMSPRO has never been approved anywhere for marketing, the firm is allowed to sell the drug in Great Britain under the country's compassionate-use regulations.
Specifically, Daval is allowed to sell the drug for use in individually named patients with a physician's prescription citing "unmet medical needs." It is produced in a licensed, government-inspected facility in Britain from serum taken from a herd of certified prion-free goats, according to Daval.
AIMSPRO's de facto availability in Britain has sparked controversy, with one newspaper reporting on patients "spending their life savings [on an] unproven goats' blood treatment."
Moore examined records of 140 patients who received the drug under the compassionate use program. The records analyzed included clinician notes, patient diaries, and questionnaire responses.
Moore determined whether improvement was present in each of the eight areas evaluated in the EDSS, using a scale that awarded two points for "marked" improvement, one point for "some" improvement," and so on to negative two points for marked worsening. "Marked" improvement in this scheme would correspond to a decrease of -0.5 EDSS points, he said.
Mean age of patients in the study was 47 (range 25 to 68) and each had received AIMSPRO for 2 weeks to 3 years. Dosing ranged from twice weekly to once every 2 weeks. The total number of doses ranged from three to 150. The mean and median duration of disease were both 14 years.
None of the patients were taking conventional disease-modifying MS drugs while on AIMSPRO.
Of the 140 patients, 122 showed improvement in at least one EDSS area, Moore reported, including 40 who had improvement in two areas, 27 improving in three, and 33 improving in four or more.
Sixteen patients demonstrated no benefit and two showed overall clinical worsening.
Data presented by Moore indicated a dose-response relationship between the total dosage received and the number of clinical areas with improvement.
Missing, though, were any data on objective measures of disease activity such as MRI lesion counts. Moore told MedPage Today that they had not been performed as part of the patients' regular care. He said MRI scans are not part of standard practice in the British system, unlike in the U.S.
Daval has completed a placebo-controlled, double-blind phase II trial of AIMSPRO in MS patients with measures of bladder function as primary outcomes, but specific results have not been reported publicly, Moore said.
According to Moore, 4 weeks of treatment did not improve bladder function, but secondary endpoints involving other MS symptoms such as walking impairments showed hints of benefit that grew during an open-label extension.
Syed Haq, MBBS, PhD, of Daval, told MedPage Today that the company had recently identified a biomarker that correlates with clinical MS severity and that is altered with AIMSPRO. He said he could not name the biomarker until the firm files a patent application, which he expected to happen shortly.
The study was supported by Daval International. One co-author was a Daval employee.
Moore reported owning stock in Daval.
Primary source: CMSC-ACTRIMS
Moore C, et al "Clinical benefits with Aimspro in progressive multiple sclerosis: Open label study" CMSC-ACTRIMS 2013; Abstract SC23.