BioMarin updates on Morquio trial

BioMarin Pharmaceutical (BioMarin) has updated on the phase I/II trial for BMN 110 or N-acetylgalact

The trial is intended for the treatment of the lysosomal storage disorder mucopolysaccharidosis type IVA (MPS IVA), or Morquio A syndrome. Preliminary clinical data from the first 24 weeks of the study (12 weeks at 0.1mg/kg and 12 weeks at 1.0mg/kg) have been evaluated. BioMarin plans to announce top-line results for the full 36-week study after completion of dosing at 2.0mg/kg in the second quarter of 2010.

Keratan sulfate (KS) levels fall within a few weeks after the start of therapy. Improvements in 6-minute walk distance and 3-minute stair climb at 24 weeks are consistent with those observed with clinical studies for MPS I, MPS II, and MPS VI. The frequency and severity of infusion reactions appear comparable to those observed with Naglazyme and Aldurazyme.

The phase I/II study is designed as an open-label, within-patient dose escalation trial in approximately 20 patients followed by a treatment continuation phase. During the dose escalation phase of the study, subjects receive weekly intravenous infusions of GALNS in three consecutive 12-week dosing intervals: 0.1mg/kg for 12 weeks, 1.0mg/kg for 12 weeks and 2.0mg/kg for 12 weeks. The objectives of the phase I/II study are to evaluate safety, pharmacokinetics, pharmacodynamics, clinical response to therapy and to identify the optimal dose of GALNS for future studies.

Hank Fuchs, chief medical officer of BioMarin, said: "Although still early, we are encouraged by these initial signals of efficacy of GALNS enzyme replacement therapy for Morquio disease. Additional results will become available following the 2.0mg/kg dose phase, but compared to other studies we have conducted in MPS diseases, we feel encouraged by the reduction in KS and improvements in walk distance and stair climb.

"Based on these results, we feel more confident about endurance as a primary endpoint for a Phase III trial and that a Phase III trial can be conducted as expeditiously as previous trials of enzyme replacement therapy. We plan to work closely with the FDA and other health authorities to finalize a Phase III protocol after the completion of the current study and have increased confidence that we will initiate a Phase III registration-enabling program by the fourth quarter of 2010 or the first quarter of 2011."

Jean-Jacques Bienaime, chief executive officer of BioMarin, said: "Based on these data, we are more optimistic about the GALNS program as we continue to move closer to providing a treatment option for Morquio patients. The number of Morquio patients identified already exceeds the number of MPS VI patients on Naglazyme, and an ERT for Morquio will fit perfectly into our global commercial infrastructure without the need for significant additional commercialization costs.

"2010 is shaping up to be an eventful year for BioMarin. In addition to results from the Morquio Phase I/II trial expected in the second quarter, we expect to report Phase II PEG-PAL results in mid-2010 and Phase I BMN 195 results in the third quarter of 2010. We look forward to keeping you updated on the progress of our clinical programs."

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Q&A: What are tax credits and how do they work?

All you need to know about the government's plan to cut tax credits.

What are tax credits?

Tax credits are payments made regularly by the state into bank accounts to support families with children, or those who are in low-paid jobs. There are two types of tax credit: the working tax credit and the child tax credit.

What are they for?

To redistribute income to those less able to get by, or to provide for their children, on what they earn.

Are they similar to tax relief?

No. They don’t have much to do with tax. They’re more of a welfare thing. You don’t need to be a taxpayer to receive tax credits. It’s just that, unlike other benefits, they are based on the tax year and paid via the tax office.

Who is eligible?

Anyone aged over 16 (for child tax credits) and over 25 (for working tax credits) who normally lives in the UK can apply for them, depending on their income, the hours they work, whether they have a disability, and whether they pay for childcare.

What are their circumstances?

The more you earn, the less you are likely to receive. Single claimants must work at least 16 hours a week. Let’s take a full-time worker: if you work at least 30 hours a week, you are generally eligible for working tax credits if you earn less than £13,253 a year (if you’re single and don’t have children), or less than £18,023 (jointly as part of a couple without children but working at least 30 hours a week).

And for families?

A family with children and an income below about £32,200 can claim child tax credit. It used to be that the more children you have, the more you are eligible to receive – but George Osborne in his most recent Budget has limited child tax credit to two children.

How much money do you receive?

Again, this depends on your circumstances. The basic payment for a single claimant, or a joint claim by a couple, of working tax credits is £1,940 for the tax year. You can then receive extra, depending on your circumstances. For example, single parents can receive up to an additional £2,010, on top of the basic £1,940 payment; people who work more than 30 hours a week can receive up to an extra £810; and disabled workers up to £2,970. The average award of tax credit is £6,340 per year. Child tax credit claimants get £545 per year as a flat payment, plus £2,780 per child.

How many people claim tax credits?

About 4.5m people – the vast majority of these people (around 4m) have children.

How much does it cost the taxpayer?

The estimation is that they will cost the government £30bn in April 2015/16. That’s around 14 per cent of the £220bn welfare budget, which the Tories have pledged to cut by £12bn.

Who introduced this system?

New Labour. Gordon Brown, when he was Chancellor, developed tax credits in his first term. The system as we know it was established in April 2003.

Why did they do this?

To lift working people out of poverty, and to remove the disincentives to work believed to have been inculcated by welfare. The tax credit system made it more attractive for people depending on benefits to work, and gave those in low-paid jobs a helping hand.

Did it work?

Yes. Tax credits’ biggest achievement was lifting a record number of children out of poverty since the war. The proportion of children living below the poverty line fell from 35 per cent in 1998/9 to 19 per cent in 2012/13.

So what’s the problem?

Well, it’s a bit of a weird system in that it lets companies pay wages that are too low to live on without the state supplementing them. Many also criticise tax credits for allowing the minimum wage – also brought in by New Labour – to stagnate (ie. not keep up with the rate of inflation). David Cameron has called the system of taxing low earners and then handing them some money back via tax credits a “ridiculous merry-go-round”.

Then it’s a good thing to scrap them?

It would be fine if all those low earners and families struggling to get by would be given support in place of tax credits – a living wage, for example.

And that’s why the Tories are introducing a living wage...

That’s what they call it. But it’s not. The Chancellor announced in his most recent Budget a new minimum wage of £7.20 an hour for over-25s, rising to £9 by 2020. He called this the “national living wage” – it’s not, because the current living wage (which is calculated by the Living Wage Foundation, and currently non-compulsory) is already £9.15 in London and £7.85 in the rest of the country.

Will people be better off?

No. Quite the reverse. The IFS has said this slightly higher national minimum wage will not compensate working families who will be subjected to tax credit cuts; it is arithmetically impossible. The IFS director, Paul Johnson, commented: “Unequivocally, tax credit recipients in work will be made worse off by the measures in the Budget on average.” It has been calculated that 3.2m low-paid workers will have their pay packets cut by an average of £1,350 a year.

Could the government change its policy to avoid this?

The Prime Minister and his frontbenchers have been pretty stubborn about pushing on with the plan. In spite of criticism from all angles – the IFS, campaigners, Labour, The Sun – Cameron has ruled out a review of the policy in the Autumn Statement, which is on 25 November. But there is an alternative. The chair of parliament’s Work & Pensions Select Committee and Labour MP Frank Field has proposed what he calls a “cost neutral” tweak to the tax credit cuts.

How would this alternative work?

Currently, if your income is less than £6,420, you will receive the maximum amount of tax credits. That threshold is called the gross income threshold. Field wants to introduce a second gross income threshold of £13,100 (what you earn if you work 35 hours a week on minimum wage). Those earning a salary between those two thresholds would have their tax credits reduced at a slower rate on whatever they earn above £6,420 up to £13,100. The percentage of what you earn above the basic threshold that is deducted from your tax credits is called the taper rate, and it is currently at 41 per cent. In contrast to this plan, the Tories want to halve the income threshold to £3,850 a year and increase the taper rate to 48 per cent once you hit that threshold, which basically means you lose more tax credits, faster, the more you earn.

When will the tax credit cuts come in?

They will be imposed from April next year, barring a u-turn.

Anoosh Chakelian is deputy web editor at the New Statesman.