EMA maintains recommendation not to grant a marketing authorisation for Glybera
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Het is niet het einde van de wereld, maar voor de paar duizend LPLD patienten wel het einde van hun hoop op een iets normaler leven. Ik ben het dan ook helemaal met prof$ eens: start een mail campagne. De verkiezingen komen er aan in dit land en dan zijn parlementariers iets bereidwilliger om te luisteren.
Dat er toch geen geld mee te verdienen was/is is voor mij niet zo heel belangrijk. Geld is inderdaad een middel. Wel heel noodzakelijk om een bedrijf (of mijn huishouden) gaande te houden, maar niet het enige doel in mijn leven.
Waar ik benieuwd naar ben welke land (persoon) er niet bij was, en hoe hij de vorige keer had gestemd.
Lijst met Standing committees, als je doorklikt krijg je gegevens over de leden.www.europarl.europa.eu/committees/en/...
BV: Industry, Research and Energy
Eén vd members: www.europarl.europa.eu/meps/en/96710/...
op deze pagina staan de contactgegevens.(Rechts op de pagina)
The Glybera Saga
Test vote: 16 to 15. Final vote: 18 to 1222.214.171.124/washington/content/pdf/...
Bedankt voor de lijst. De eerste hengels zijn uitgegooid. Deze uitslag vraagt om een herziening van de regels, of beter gezegd meer lef en ondernemerschap van de CHMP en EC leden. Het is onze taak als goed EU burger hen daarop te wijzen.
Bij een zware negatieve opinie had ik mij er allang bij neergelegd, maar deze uitslag (de stem uitslag en onderbouwing) verdiend een heroverweging voor goedkeuring onder bijzondere omstandigheden. Het is een kleine moeite mensen in positie er op te wijzen. Niemand heeft vooraf gezegd dat het makkelijk zou worden om de eerste gen therapie goedgekeurd te krijgen en kennelijk is dit de weg die afgelegd moet worden.
Don’t put the kibosh on innovation
Nuala Moran, Science|Business
The European Medicines Agency’s thumbs-down for rare disease treatment Glybera flies in the face of Commission policy. It’s also against the wishes of the European Parliament, and the impetus DG Sanco is putting into Orphan Drugs. Worse still, it’s bad for patients and kills innovation. By Nuala Moran.
It’s very far from being a potential blockbuster, but for those few people afflicted by the inherited disorder for which it tailored, it is a wonder drug.
Glybera is a treatment for lipoprotein lipase deficiency, an ultra-rare condition in which patients lack an enzyme that is essential for breaking down fat. As a result, tiny fat globules accumulate in the pancreas, causing swelling and - painful – recurrent attacks of pancreatitis.
There are estimated to be 4,000 people with the disorder worldwide. Overall, the 27 sufferers that have taken part in clinical trials had fewer acute attacks of pancreatitis after receiving Glybera.
But sadly the treatment – developed at great expense over 14 years by the Dutch gene therapy specialist Amsterdam Molecular Therapeutics – was last week turned down for the third time by the European Medicines Agency (EMA).
This is not because of any concerns over the safety of using a virus to deliver a correct copy of the aberrant gene, but because EMA’s Committee for Medicinal Products for Human Use (CHMP) ruled the small number of patients who took part in trials means there is not sufficient evidence to demonstrate Glybera is effective.
EMA experts recommended Glybera approval
The CHMP reached this conclusion despite the fact that two other EMA expert bodies, the Committee for Advanced Therapies (CAT), which was set up specifically to provide guidance to the CHMP on gene therapies, and EMA’s Scientific Advisory Group, which advises on the science and biology behind novel products, both recommended Glybera be approved.
What’s more, the CHMP was considering Glybera for the third time because in January the European Commission made an unprecedented move, refusing to put its usual rubber stamp on the CHMP’s earlier recommendation that the product should be refused, and instructing the Committee to think again.
Lack of transparency
Yet more egregiously still, the CHMP itself voted 16 – 15 in favour of approving Glybera at its meeting last week. Unfortunately, for a product to get the nod it needs an absolute majority – or 17 votes – from all the members of the 32-strong committee, not just members who are present to vote. Members who are not present cannot vote in absentia.
For Jörn Aldag, CEO of Amsterdam Molecular Therapeutics (AMT), the lack of transparency is unacceptable. The rules need to be made clear because otherwise people just won’t make the investment, he says. AMT itself is now in liquidation, the assets have been transferred to a new company uniQure BV, and there will be no further investment in Glybera.
Bureaucracy gone bonkers
As Alastair Kent, one of Europe’s leading advocates for people affected by genetic disorders put it, "this is bureaucracy gone bonkers".
The CHMP is not only flying in the face of the policy of the European Commission, it is also acting against the express wishes of the European Parliament and the impetus that the European Union’s health directorate DG Sanco is putting behind the development of new treatments for rare diseases.
For Kent, who is Director of Genetic Alliance, a body representing 150 UK patient organisations, and a former member of CAT, the Glybera decision has even wider implications "Frankly, it’s discriminatory to those affected by rare diseases to set the evidence bar at an impossible height, and demand standards of proof it is impossible to provide," he told Science|Business.
The ripples could go further, to halt development of personalized medicines, Kent believes. "When you put common diseases into subsets, you can’t go down the traditional, controlled-trials approvals route," he said.
The Glybera controversy is also a test for the recently installed head of EMA, Guido Rasi, who has pledged greater transparency in the way the Agency operates. To date this has consisted of flooding EMA’s website with thousands of pages of documents, creating a data deluge with the potential to cause greater obfuscation.
How the EMA explains its decision on Glybera will be a far better measure of improvements in transparency.
This is critically important, because the end result of the lack of transparency and clarity in EMA’s rules and procedures will be to "kibosh innovation" Kent says. The people who are losing out are researchers, the industry, and most importantly the patients who are left with potentially avoidable ill health, he says.
Thanks, Good article!
Everybody, keep on forwarding those artices to members of the EC!
Nog altijd !!! Waar zijn jullie in godsnaam mee bezig , Jezus Christus !
Jezus is al lang dood en god woont in Griekenland.
Nog steeds gezond...mooi, geniet ervan!
" Habemus Papam " contradictie , hier komt geen nieuwe !
De Ema heeft zijn opinie gegeven. Hoeveel dagen mag de ec er over doen om hun oordeel te geven?
3 maanden zal het duren voor dat de ec zijn oordeel geeft
Brief Genetic Alliance UK.
Letter to the European Commission regarding innovative therapies
The European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) voted against the advice of its expert sister committee, the Committee for Advanced Therapies (CAT) this week, when it decided against granting a market authorisation for an innovative therapy for lipoprotein lipase deficiency (LPLD). LPLD is a genetic condition which affects the digestion and processing of lipids. It causes severe pancreatic problems and abdominal pain. More details are available here.
We wrote to the European Commission to express our concern that initiatives to allow innovative therapies to be developed in the EU (such as the Committee for Advanced Therapies) are being side-lined by the refusal of the CHMP to accept their expert views.
Ms Paola Testori Coggi
Directorate-General Health & Consumers
B - 1049 Brussels
25 April 2012
Dear Ms Testori Coggi,
I write to protest at the perverse decision by the Committee for Medicinal Products for Human Use (CHMP) to reject the application for a Marketing Authorisation for Glybera.
Genetic Alliance UK has over 150 patient organisations in membership representing and supporting individuals and families affected by all forms of genetic disease. As such we take a keen interest in the regulatory framework that determines whether or not scientific advances can be translated into innovative therapies quickly, safely and affordably so those who need to use them are able to access them.
As we understand the situation, the Glybera dossier was developed following scientific advice from the agency by experts knowledgeable in developing appropriate clinical trials capable of delivering evidence necessary to inform regulatory decisions.
The CAT, the committee best qualified to judge quality safety and efficacy of advanced therapies, was strongly supportive of the case for granting a Marketing authorisation. The CHMP’s rejection of the CAT position must put these two bodies on a collision course. It would certainly undermine the willingness of any independent expert to serve on a committee which can be sidelined in this way.
There was a majority of CHMP members present and voting in favour of granting the Marketing Authorisation but due to the rules of procedure this majority view was not carried because there was no absolute majority of the whole committee membership so it did not count and the application fell. Of course you know all this, and doubtless the excuse for this bizarre decision will be “It’s the rules”.
However much this may be the case, if the rules lead you into a position which those looking in find untenable, then the system needs to be changed and changed quickly.
Here we have a product for a disease which has no other effective intervention. At least some of those participating in the clinical trial felt significant benefit from their participation, being able to adopt a more normal diet and enjoying an improved quality of life as a result. There were no significant safety concerns revealed in the development process – the CHMPs concerns were about efficacy. Rejecting this application effectively leaves no route for these to be addressed. Conditional approval would have made the collection of this data mandatory, allowing the CHMP’s concerns to be addressed.
It appears that the CHMP has judged Glybera on criteria designed for the regulation of the traditional medicines for large populations. In doing so, it has flown in the face of more than a decade of European policy that has been aimed at building a framework in which novel therapies can be assessed by experts and can be regulated appropriately with realistic requirements for evidence provision which take account of the population sizes that are likely to be involved.
As things stand this is likely to be the end of the road for Glybera, leaving a group of patients with a significant unmet medical need without hope for an improvement in their condition. This is bad enough in itself, but this perverse result is likely to have significant knock-on consequences for the future development of therapies for patients with very rare conditions. This will undermine the Commission’s efforts to promote this as an economic and a public health priority for Europe. The difficulties in generating evidence in support of interventions targeted at very rare conditions are well demonstrated. If the CHMP insists on setting the bar for obtaining Marketing Authorisation unreasonably high then the willingness of investors to take the risk and invest in the development of innovative therapies will disappear. The pharmaceutical industry is currently putting significant sums behind the development of orphan drugs, but this will stop if the regulatory framework is deemed to be making it impossible to anticipate a positive outcome. The Commission’s own investment in the International Rare Disease Research Consortium and other initiatives in this field will be wasted if the evidence requirements of the CHMP make orphan drugs too expensive to develop, and the consequences for patient access for those which do manage to leap the hurdle are likely to be significant in European Health Care Systems struggling to meet patients needs in times of severe downward budgetary pressures and rising demand.
I cannot believe that this is a consequence that you would welcome, and I imagine that you would struggle to justify this outcome to the millions of patients with rare diseases who have seen the progress made since the adoption of the Orphan Medicinal Products Regulations as one of the Commission’s most important achievements for many years. I also think the Parliament, which has systematically championed the issue of meeting rare disease patients’ needs would be dismayed by this outcome.
We would urge you not to accept the CHMP’s recommendation, but either to refer it back for further consideration or over-ride the decision they have recommended as a matter of urgency.
As you may be aware, I was a member of the COMP for six years, and more recently of the CAT. I resigned my membership of the CAT in protest at the rules on conflicts of interest adopted by the EMA as I felt these were likely to increase the difficulties for the Agency in engaging with key experts in the field, reducing the confidence that patients and citizens have in the ability of the EMA to regulate on their behalf. Neither I, nor Genetic Alliance UK, nor any other organisation with which I may be associated has any financial stake in the outcome of the Glybera application. I write because this is a perverse decision that will harm the interests of patients and families with rare diseases and which will have potentially significant adverse consequences for the whole thrust of research and development in the personalised medicine field. This will frustrate patients’ expectations for progress in addressing unmet health needs, increase inequalities and damage European competitiveness just at the point where advances in research are poised to deliver significant advances through the application of innovation.
I look forward to your response.
Alastair Kent OBE
Genetic Alliance UK
European Genetic Alliances’ Network
Professor Guido Rasi
European Medicines Agency
Is het wel een gebeurt dat de Ec niet de opinie van de CHMP over neemt?
Nee, maar de CHMP neemt ook altijd het advies van de CAT over. Goede brief dus en misschien moeten we er nog een paar met die strekking sturen.
Gr :) Frank
The EMA’s Shambolic Handling of Glybera
If you can’t see the wood for the trees the common sense response is to do a little thinning and let the light shine through.
But for the bogged-down-in-bureaucracy European Medicines Agency (EMA), the response last week to the need to increase transparency and streamline its procedures was to set up an expert committee to investigate the activities and operations of its expert committees.
I don’t imagine this is a cynical move by the recently installed head of EMA, Guido Rasi, to kick complaints about a lack of transparency and failure to listen to the needs of patients into the long grass. He knows prevarication won’t magic the issue away.
But a committee to investigate your committees – please!
The immediate reason for the EMA to announce the formation of its scientific coordination board was its embarrassment around the rejection in April – for the third time – of Glybera, a gene therapy treatment for the ultra-rare inherited disorder lipoprotein lipase deficiency developed by Amsterdam Molecular Therapeutics Holding NV.
The EMA’s Committee for Medicinal Products for Human Use (CHMP) ruled that although it had no safety concerns the small number of patients who took part in trials meant the data file did not demonstrate that Glybera is effective in limiting the acute attacks of pancreatitis that are the most insidious manifestation of the disorder.
The CHMP exercised its prerogative despite that fact that two other EMA expert bodies, the Committee for Advanced Therapies and the Scientific Advisory Group, recommended Glybera be approved under exceptional circumstances.
Rasi previously told BioWorld it was not surprising that EMA committees had reached differing conclusions, since they are independent of each other. Well maybe not, but there’s little point in preserving the independence of your experts, if the result is to render your organization sclerotic. The EMA needs to function.
What makes the case even worse is that the CHMP members who were at the meeting to consider Glybera voted 16-15 in favor of its approval. Unfortunately, it requires 17 votes for a product to be recommended for approval.
Even without knowing which way the missing 32nd member of the CHMP might have cast her or his vote, it is clear a majority of expert opinion believes Glybera should be allowed on the market and given an opportunity to build its case.
The many levels at which the shambolic handling of Glybera is reverberating are eloquently expressed in a letter that Alastair Kent, director of the UK charity The Genetic Alliance, wrote to the head of the European Commission’s Directorate for Health and Consumers protesting at the CHMP’s decision.
If there is a single good reason – beyond the procedural – why Glybera should not be approved under exceptional circumstances to allow efficacy data to accumulate, the EMA should say what it is.
Now that would be transparency.
The Efficacy Sticking Point in the Post-Glybera Era for Gene Therapies and Ultra Orphan Drugs
Cameron Lockwood · June 5, 2012
This April, Glybera (alipogene tiparvovec), a gene therapy developed by Dutch firm Amsterdam Molecular Therapeutics (AMT) for use in patients with lipoprotein lipase deficiency (LPLD), finally received a negative approval recommendation from the EMA’s approvals committee CHMP. Glybera, which had been expected by some to become the first gene therapy approved in Europe, took something of a circuitous and protracted path through the EMA—one with potentially important lessons for gene therapies and (ultra) orphan drugs more generally.
Efficacy Criteria and (Ultra) Orphan Drugs
The CHMP previously issued two negative recommendations for Glybera. April’s recommendation came after considering approval in a subset of patients at the request of the European Commission Standing Committee. While it is significant—and a testament to scientific progress—that serious concerns over safety did not figure in the CHMP’s recommendation, questions over efficacy did—something which has proved to be a sticking point before, notably in the case of Ark Therapeutics’ Cerepro, another candidate once hoped to be the first gene therapy to be approved in Europe.
LPLD, currently lacking treatment options, is an ultra-rare autosomal recessive disorder in which failure to metabolise chylomicrons leads to severe hyperlipidaemia and recurring pancreatitis. AMT relied on three trials for its evidence base:
• CT AMT-010: enrolled 8 patients and assessed reduction in median fasting plasma triglyceride concentration;
• CT AMT-011-01: enrolled 14 patients and also evaluated effect on fasting triglyceride; and
• CT AMT-011-02: enrolled 5 patients and evaluated the effect on postprandial chylomicron metabolism, as well as plasma fatty acid and glycerol appearance rates
In its final recommendation, the CHMP considered that there was insufficient evidence of persistence of effect shown in a ‘clinically relevant manner,’ and that improvements in pancreatitis risk could have been due to other factors. The CHMP also determined that long-term data were not available for a sufficient number of patients.
One can wonder whether, in reaching this conclusion, the CHMP has not set the bar too high for many ultra-orphan drugs. As an ultra-rare disorder, LPLD is estimated to affect around one to two people per million, therefore challenging attempts to recruit sufficient patient numbers. In terms of clinical trial design, there has been some debate over choice of endpoints, with the correlation between plasma triglycerides levels and incidence of pancreatitis called into question. Indeed, prior to the final CHMP outcome, the CEO of AMT is quoted as saying that he believed the EMA would accept chylomicron levels as a better marker for reduction in pancreatitis risk; the company had hoped that post-hoc analysis of chylomicron levels in patients not in the CT AMT-011-02 trial would address CHMP concerns over efficacy. As pointed out by Alastair Kent OBE, Director of Genetic Alliance UK and President of the European Genetic Alliances’ Network, AMT had in fact availed itself of scientific advice on trial design made available by the EMA.
And Let’s Not Forget What Lies Downstream…
Having recently participated in our study on what payers look for in relative effectiveness assessment, I would be interested to know how these stakeholders would respond to the evidence base supplied by AMT…especially given our finding that, though a number of countries may in theory have policies for relaxing reimbursement decision-making criteria for orphan drugs (or ‘rules of rescue’ may operate for those diseases with no existing treatment options), in practice, there are many examples of candidates failing at this hurdle.
With a growing number of candidates in the gene therapy pipeline, it shouldn’t be long before another aims to make it past the regulatory post—and, when this occurs, it will be very interesting to see how European payers react to the efficacy issue.
Enig idee wanneer de EC tot haar besluit komt?
Het zal vast niet lang meer duren... een mooie gelegenheid voor ze om leiderschap te tonen!
Oooooooo wat zal ik blij wezen als er
eens goed(keuring)bericht zou komen ,
Ziezo! En nu niet meer zeggen dat lobbyen geen zin heeft.
Ziezo! En nu niet meer zeggen dat lobbyen geen zin heeft.
?? ; Is er al een indicatieve prijs op de interne markt, of nog steeds die 34 cent van voor goedkeuring ? Ik heb mijn stukken nog niet aangemeld op NPEX dus ken de ins en outs niet op het ogenblik...
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