Lysosomal Diseases New Zealand

Lysosomal Diseases New ZealandLysosomal Diseases New ZealandLysosomal Diseases New ZealandLysosomal Diseases New Zealand

New Zealand Lysosomal Storage Diseases New Zealand Lysosomal Storage Diseases New Zealand Lysosomal Storage Diseases New Zealand Lysosomal Storage Diseases

Support GroupSupport GroupSupport GroupSupport Group

John Forman

+64 4 566-7707

Jenny Noble

+64 7 544-8868

www.ldnz.org.nz

Our mission

To improve contacts, information sharing and support among

affected people and their families, within New Zealand and

Internationally.

To advocate for and support accelerated research into the causes

and treatment of Lysosomal Storage Diseases.

To advocate for, and support improvements to the clinical care of

affected people.

Individual HighlightsIndividual HighlightsIndividual HighlightsIndividual Highlights

Kyphos Corner

John Hopwood – receives Life

Time Award

Phase 2 Clinical Trial of

AT2220 in Pompe Disease

Clinical Trial for Juvenile

Batten Disease

Clinical Trial of Plicera(TM) for Gaucher Disease

And so much moreAnd so much moreAnd so much moreAnd so much more

Special EventsSpecial EventsSpecial EventsSpecial Events

Charity Golf

Call for Posters from 2008

Lysosomal Conference

AAAAugustugustugustugust Newsletter 2008 Newsletter 2008 Newsletter 2008 Newsletter 2008

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Lobbying for funding for enzyme replacement therapies Lobbying for funding for enzyme replacement therapies Lobbying for funding for enzyme replacement therapies Lobbying for funding for enzyme replacement therapies ––––

the priority issue for LDNZ.the priority issue for LDNZ.the priority issue for LDNZ.the priority issue for LDNZ.

The number of ERTs for lysosomal diseases has increased quite rapidly in recent years from just one treatment to a total of

six. This has meant the issue of funding for New Zealand patients has become increasingly important because the

additional five treatments have moved from theoretical possibilities in clinical trials to a reality of medicines now

available on the market.

The significant public debates about the adequacy of New Zealand’s pharmaceuticals budget, and also the approach that

Pharmac has taken towards high cost medicines for other diseases, has meant that LDNZ has been acutely aware of these

issues and has been working hard over recent years to prepare for the arrival of these new treatments and improve the

chance they will be funded.

• We have taken a leadership role in the Access to Medicines Coalition to get a medicines strategy put in place

with an improved set of decision criteria that now apply to future applications. Especially important to us is that

issues like reducing inequalities, access to medicines regardless of individual ability to pay, and equity, are now

a formal part of the decision process. Previously such items were not stated and there was a huge reliance on

cost issues alone.

• We have lobbied hard to get political acceptance of the need for increased investments in medicines. This has

been a very difficult task but one major political party has now accepted the need for this, and there are signs

others may be willing to commit to this also. Meetings have been held with politicians and more will occur in

the lead-up to the election.

• We have worked closely with the pharmaceutical companies to advise them on strategies to improve the

chances of ERTs being funded. We have encouraged them to register all the treatments with Medsafe, the

medicines regulator, to ensure all the preliminary steps in the process are fully covered, so Pharmac would not

be able to use non-registration as an excuse for inaction on their part.

• We have briefed Pharmac on several occasions over the past few years about ERTs for Lysosomal diseases so

they are well aware of the need and the importance of these therapies.

• We have pushed for central co-ordination of clinical care for all Lysosomal patients under the Metabolic Service

to improve the medical expertise available. This should have the added benefit of ensuring that the best

treatment will be considered at the right time. We are making some progress on this goal following support given

to our case by the Health & Disability Commissioner, briefing given to the Minister of Health, and in discussions

with the Ministry of Health.

• We have closely monitored Australian approval processes so we are aware of criteria in our closest neighbour,

and the timing of their funding decisions. Things are difficult there too, with only three of the treatments currently

approved for them. We are unlikely to win funding here prior to treatment being funded in Australia.

During 2008 there has been increased effort by LDNZ to secure ERT for Lysosomal patients in New Zealand. We still

have some way to go to achieve that goal, but we think the path has been made a little smoother and our chances

improved by the priority this work has been given over the past several years. We will keep you briefed on other steps we

take.

John FormanJohn FormanJohn FormanJohn Forman ChairpersonChairpersonChairpersonChairperson

Kypho’s CornerKypho’s CornerKypho’s CornerKypho’s Corner


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Prof Prof Prof Prof John Hopwood receives Life Time AwardJohn Hopwood receives Life Time AwardJohn Hopwood receives Life Time AwardJohn Hopwood receives Life Time Award

New Families

We warmly welcome to our We warmly welcome to our We warmly welcome to our We warmly welcome to our Lysosomal Lysosomal Lysosomal Lysosomal familyfamilyfamilyfamily

Anna Percy Mark Wilson and their children

Natasha, 7, Kirsty 11, Reuben 14 and Oliver 16

who has Fabry

U P C O M M I N G E V E N T S

2 0 0 8 - 2 0 1 0

♦ LDNZ Charity Dinner Palmerston NorthCharity Dinner Palmerston NorthCharity Dinner Palmerston NorthCharity Dinner Palmerston North

13th September 2008 ♦ LDNZ Charity Golf Day - Timaru

10th October 2008

♦ 1111stststst AsiaAsiaAsiaAsia---- Pacific LysosomalPacific LysosomalPacific LysosomalPacific Lysosomal ConferenceConferenceConferenceConference and 12and 12and 12and 12 thththth

National Australian MPS ConferenceNational Australian MPS ConferenceNational Australian MPS ConferenceNational Australian MPS Conference

20th—23rd November 2008 Christchurch

♦ 11th International symposium11th International symposium11th International symposium11th International symposium forforforfor

Mucopolysaccharide and Related Diseases Mucopolysaccharide and Related Diseases Mucopolysaccharide and Related Diseases Mucopolysaccharide and Related Diseases 23rd – 26th June 2010 – Adelaide

Prof John Hopwood has spent more than 25 years researching and finding treatments for Lysosomal Diseases. During the gala dinner at the 10th International Symposium on Mucopolysaccharide and Related diseases in Vancouver, John received a Life time award for his work. John said during his acceptance speech “This has been a fantastic journey. My passion, and what has driven me for my entire career, has been to see LSD patients effectively treated,” LDNZ congratulates John on this prestigious and much deserved award.


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Attending the 2008 International Symposium was extremely positive both for LDNZ and 2010 International Symposium committee who were there to showcase Adelaide and New Zealand. Our wonderful posters that we developed over a year ago were a great hit among families and professionals. I was very impressed by the number of people stopping by to take photographs of our posters. People were very keen to learn more about our unique animal models of Lysosomal diseases in New Zealand.

Lysosomal Diseases Australia (LDA) the Australian MPS Society and LDNZ hosted the 2010 International symposium booth. We had our advance information postcards and 1,000 chocolate frogs to hand out to everyone. They certainly were a wonderful way to break into the many conversations going on, introduce ourselves and invite people down under in 2010. We were highly visible throughout the conference with our shirts with the 2010 logo on. Towards the end of the conference, we were being teased about the amount of advertising we were doing. Every presentation John Hopwood and his team from Adelaide made, they finished with a photo of Adelaide and ‘join us down under for 2010join us down under for 2010join us down under for 2010join us down under for 2010’’’’....

The conference itself was really interesting John Hopwood from Australia opened the conference and spoke about the

advances in LSD’s and the hurdles still to come and these include: Treating CNS, New born screening , early detection,

prognosis in asymptomatic patients, Lysosomal dysfunction, irreversible pathology, and maintaining long term treatment.

Some of the other topics covered were the Skeleton and connective tissue in the MPSs., therapies for the MPSs and this

covered the existing therapies and some that are out on the fringe.

Dr Joe Munzer (USA) spoke on ERT experiences in the MPSs and the challenges that still face researchers. These include:

Why CNS does not stabilize after BMT, why skeletal disease does not respond to ERT or BMT, what dose is needed in

attenuated patients to maintain function (at present everyone gets the same dosage), what is the impact antibiotics have

on clinical outcomes, can somatic disease be prevented if treatment is started before the onset of symptoms and is new

born screening needed.

Welcome Reception Welcome Reception Welcome Reception Welcome Reception

The welcome reception was held on the Thursday evening among the ‘Expression of Hope’ artwork, the exhibition

booths, Poster displays and the MPS Society displays. This was a great time to network with professionals and be able to

talk to families and to promote the next International symposium in Adelaide, South Australia 2010. To view the

expressions of hope go to. www.expressionofhope.com

10101010 thththth International Symposium on MucopolysacchaInternational Symposium on MucopolysacchaInternational Symposium on MucopolysacchaInternational Symposium on Mucopolysaccharide and Related ride and Related ride and Related ride and Related

diseasesdiseasesdiseasesdiseases 26262626 thththth –––– 29292929 thththth June 2008June 2008June 2008June 2008


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International International International International MPS MPS MPS MPS Network meetingNetwork meetingNetwork meetingNetwork meeting

It was wonderful to be able to attend this meeting again and to be able to network with other support group leaders from

around the world. The international network committee comprises of MPS and Lysosomal support groups leaders on a

global basis.

The agenda was very full with invited presenters who spoke to us about

• ERT for MPS IV – where are we and where are we going

• Disease Registries

• Updates on Blood Brain Barrier Research

• Updates on BRAINS FOR BRAINS

It is at this meeting that those wishing to host the International symposiums present their bids. Taiwan and Netherlands

were bidding for 2012 International MPS Symposium. The 2012 International MPS Symposium went to the Netherlands.

We will be seeing Taiwan bid again in 2010 for the 2014 International symposium. I truly hope that this is where we see

the 2014 conference go as there is much work to be done in the Asian region.

It is certainly very interesting to hear how other groups advocate for their diseases and where they are supporting

research. I see this committee as being very useful to LDNZ and in particular a place where we can ensure that the super

orphan diseases within our group are not forgotten.

What is Brains for Brain

B4B is a research task force formed by scientists with the major aims to create and coordinate research to enable a better

understanding of the neurological problems that occur in Lysosomal Storage Diseases, and then use their knowledge on

the Blood Brain Barrier to develop strategies to overcome the BBB and treat neurological disorders.

Why Brains for Brain and B4B nicknameWhy Brains for Brain and B4B nicknameWhy Brains for Brain and B4B nicknameWhy Brains for Brain and B4B nickname

The task force takes advantage of the expertise of the most distinguished European scientists, leaders in basic and applied

neurotechnology and neurology grouped together to create a coordinated effort toward the comprehension of

pathophysiology processes of neurological disorders in LSDs, the implementation of knowledge on the blood brain

barrier and the development of new molecular and or biochemical strategies to overcome the blood brain barrier to treat

these CNS disorders. The B4B nickname of the group has been chosen to acknowledge the effort of the 4 initial sponsors

(ACTELION, BIOMARIN, GENZYME and SHIRE Human Genetic Therapies) without which this brainstorming panel

could not have been created

For more information please see the website: www.brains4brain.eu

John Hopwood and Jenny Noble in the Shirts

worn during conference with the 2010 logo Virginia Taiwan MPS Society


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Amicus Therapeutics, a biopharmaceutical company developing small molecule, orally-administered pharmacological chaperones for the treatment of human genetic diseases, today announced that it has initiated a Phase 2 clinical trial of AT2220 (1-deoxynojirimycin HCl), for the treatment of Pompe disease. Amicus will conduct the study in adult Pompe patients in clinical centers throughout North America and Europe. AT2220 is the third compound based on Amicus' pharmacological chaperone technology platform to enter Phase 2 clinical development.

"We look forward to evaluating AT2220 as a potential new oral therapeutic option for patients living with Pompe disease," said Barry J. Byrne, M.D., Ph.D., professor of pediatrics, molecular genetics and microbiology at the University of Florida in Gainesville and an investigator in the Phase 2 trial.

AT2220 is designed to selectively bind to, stabilize and elevate the cellular activity of acid alpha-glucosidase (GAA), the enzyme deficient in Pompe disease. This deficiency leads to lysosomal accumulation of glycogen inside cells, which is believed to cause the various symptoms of Pompe disease.

Amicus is initiating the multi-national, open-label Phase 2 clinical trial designed to enroll 18 adult patients diagnosed with Pompe disease. The primary objective of the study is to evaluate the safety and tolerability of different dosing regimens of AT2220 over a 12-week period. The study will also explore certain pharmacodynamic and pharmacokinetic measures including the effect of treatment with AT2220 on GAA activity and on glycogen levels in various cells and tissues. Additional objectives include preliminary assessments of pulmonary and skeletal muscle function. Participants who complete the study may be eligible to participate in a voluntary extension study that will further evaluate the effect of AT2220 on these functional parameters.

Additional information about the Phase 2 study will be posted at Additional information about the Phase 2 study will be posted at Additional information about the Phase 2 study will be posted at Additional information about the Phase 2 study will be posted at www.ClinicalTrials.govwww.ClinicalTrials.govwww.ClinicalTrials.govwww.ClinicalTrials.gov

We did have some down time before our meetings and

conference. Paul got friendly with a Canadian while we

were sitting having lunch one day. He happened to

notice two very different accents and wanted to know

where we were from. He eventually asked us if we had

ever been to a ball game, and promptly invited us to join

him. What a blast.

The girls were right behind the batting pitch while Paul

was with Tom somewhere off to the side!!!!! Tom was

fantastic he drove us all around Vancouver and showed

us all the sights and ensured we all had a great time.

Amicus Therapeutics Begins Phase 2 Clinical Trial of AT2220 in Pompe DiseaseAmicus Therapeutics Begins Phase 2 Clinical Trial of AT2220 in Pompe DiseaseAmicus Therapeutics Begins Phase 2 Clinical Trial of AT2220 in Pompe DiseaseAmicus Therapeutics Begins Phase 2 Clinical Trial of AT2220 in Pompe Disease


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FUN

Fundraising plays a very important role in how LDNZ is able to function. We began this huge task last year with our very

first charity dinner held in Tauranga in 2007; our next Charity Auction Dinner is being held in Palmerston North. Kirsty

Peacock mum to Jack, (Hunter syndrome), has taken on the role of doing the organizing for September 2008. LDNZ is

very grateful to her for taking this on. It allows Jenny to get on and concentrate on the conferences that LDNZ is

committed to in 2008 and 2010.

Each and every Lysosomal family can play a role in helping us raise the much need funds. Imagine if you all went out . Imagine if you all went out . Imagine if you all went out . Imagine if you all went out

and raised and raised and raised and raised just $200just $200just $200just $200 ---- spreadspreadspreadspread over 90 families this would raise $18,000.over 90 families this would raise $18,000.over 90 families this would raise $18,000.over 90 families this would raise $18,000. Imagine how much research we could

support based on this kind of fundraising. One Lysosomal mum in Timaru has set out to do just that. She is organizing

our first ever Charity Golf day with guest players such as our very own Prof. David Palmer from Lincoln University,

Christchurch and ex All Black Stu Wilson. Below are details of the Charity Golf day to be held on 10th October 2008.

Check out our website for more details. You can all play a role in helping us raise much need funds to support families

wanting to attend disease specific conferences, research and the mission of LDNZ.

Lysosomal Diseases New ZealandLysosomal Diseases New ZealandLysosomal Diseases New ZealandLysosomal Diseases New Zealand

Proudly supported by Highfield Golf Course Invites you to our

Charity Golf DayCharity Golf DayCharity Golf DayCharity Golf Day

10th October 2008

Special Guest Players Special Guest Players Special Guest Players Special Guest Players

Stu Wilson

Ex All Black and All Black Captain

Prof David Palmer

Leading Researcher from Lincoln University

Venue Highfield Golf Course

Registrations commence 10.00am

Prize Giving

and Meal to follow Ambrose

$200 per group of 4

Raffles and Charity Auction

BBQ on 10th Hole $1.00 sausage/Pattie

RSVP Mark Timms

Phone 03 684-6481 or 021 277-4651 Dinks & BBQ tent on

11th Hole

Ra Timms 03 684-6481 or 032 477-006

Estimated finish time 3.30 – 4.00pm

FUNDRAISINGFUNDRAISINGFUNDRAISINGFUNDRAISING


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A Clinical Trial for Juvenile Batten Disease by David Pearce, Ph.D.

Background

Batten disease, a childhood neurodegenerative disorder results from mutations in the gene known as CLN3. At present, we are only able to treat the symptoms of Juvenile Batten disease. Thus, there is a real need to intervene and slow the progression of this disease. Research has shown that patients with juvenile Batten disease and a genetically similar mouse, known as the CLN3 knockout mouse, that serves as a model for the study of this disease both have an abnormal immunological response. This abnormal immunological response suggests that something happens to the immune system that can result in the immune system literally turning on the patient in much the same way a virus would be attacked, except that the patient's own proteins are targeted. It is proposed that this “autoimmune response” contributes at least partially to cause of juvenile Batten disease. Therefore, a research strategy to block this autoimmune response has been tested in the CLN3 mice.

Two strategies were used to block or “immunosuppress” the immune response in the mice. First, the CLN3 mice were altered genetically to be unable to generate B-cells that produce the autoantibodies, and secondly the CLN3 mice were given a daily dose of the drug, Mycophenolate Mofetil (CellCept), that suppresses B-and T-cell production. For both strategies, CLN3 mice were monitored for a decline in a basic neurological motor function test. Remarkably, genetic and drug induced immunosuppression slowed the decline in motor or physical function in the CLN3 mice.

Significance Significance Significance Significance

The use of Mycophenolate Mofetil (CellCept) is the FIRST demonstration of a reduced disease state in the CLN3 mice. This strategy is not a symptomatic treatment. While we have shown that a decline in motor function in the CLN3 mouse may be slowed, Mycophenolate Mofetil (CellCept) was chosen to target the disease itself.

What's next?What's next?What's next?What's next?

While we have shown that immunosuppression strategies slow the decline in motor/physical function in the CLN3 mice, we need to examine in more detail other aspects of declining neurological function in juvenile Batten disease. This will provide a greater understanding of the treatment strategy as well as provide further details on how broadly this approach will impact disease progression.

NEVERTHELESS, the use of Mycophenolate Mofetil (CellCept) is the first demonstration of a reduced state of disease in CLN3 mice. Mycophenolate Mofetil (CellCept) is used as an immunosuppressive agent in organ transplants in children and is therefore approved for pediatric use as data indicates an acceptable level of side effects in children with a life threatening disease. Therefore, due to the nature of juvenile Batten disease it is reasonable to plan a clinical trial that will test the effectiveness of Mycophenolate Mofetil (CellCept) as a treatment for juvenile Batten disease.

How? How? How? How?

The Batten Center at the University of Rochester Medical Center has the infrastructure in terms of expertise in juvenile Batten disease to perform a clinical trial. However, the design of a trial that will test whether a drug successfully treats a disease requires expertise of individuals who have performed prior clinical trials. Planning and meeting regulatory requirements will require many hours and funding for both design and implementing this trial.


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For Immediate ReleaseFor Immediate ReleaseFor Immediate ReleaseFor Immediate Release:

BioMarin Announces Program for ERT for Treatment of MPS IVA BioMarin Announces Program for ERT for Treatment of MPS IVA BioMarin Announces Program for ERT for Treatment of MPS IVA BioMarin Announces Program for ERT for Treatment of MPS IVA –––– Morquio A SyndromeMorquio A SyndromeMorquio A SyndromeMorquio A Syndrome Novato, Calif, June 5, 2008 – BioMarin Pharmaceutical Inc. (Nasdaq and SWX: BMRN) today announced its program for

its third enzyme replacement therapy (ERT) for the treatment of mucopolysaccharidosis IVA (MPS IVA), or Morquio A

Syndrome. BioMarin plans to initiate a Phase 1/2 clinical trial in the first quarter of 2009.

"With two MPS drugs on the market, we plan to leverage our clinical, manufacturing and regulatory expertise to

efficiently develop a treatment for Morquio patients," said Emil Kakkis, M.D., Ph.D., Chief Medical Officer of BioMarin.

"Our planned program includes a clinical assessment study to measure the depth and breadth of disease as well as a

separate GALNS Phase 1/2 study in Morquio Type A patients. Preliminary studies are promising and indicate that our

drug candidate binds naturally to bone matrix and can adequately reach the growth cartilage after IV infusion. The

skeletal system disease is a primary concern in the treatment of this disease."

The company has successfully developed and manufactures two FDA-approved enzyme replacement therapies for the

treatment of MPS I and MPS VI. Naglazyme® (galsulfase) MPS VI is wholly developed and commercialized by BioMarin.

Aldurazyme® (laronidase) for MPS I is manufactured by BioMarin and marketed by Genzyme Corporation. Additional

details of the MPS IVA program, along with an overview of BioMarin's product portfolio, advancements in the research

and development pipeline and other ongoing programs will be provided today at BioMarin’s R&D Day program in New

York City. Interested parties may access a live audio webcast of the presentation via the investor section of the BioMarin

website, http://www.BMRN.com. A replay of the presentation will be archived on the site for at least one week following

the presentation. For general inquiries, please email [email protected].

About MPS IVAbout MPS IVAbout MPS IVAbout MPS IV

Mucopolysaccharidosis IVA (MPS IVA, also known as Morquio A Syndrome) is a disease characterized by deficient

activity of N-acetylgalactosamine-6-sulfatase (GALNS) causing excessive lysosomal storage of keratan sulfate (KS). This

excessive storage causes a systemic skeletal dysplasia, short stature, and joint abnormalities, which limit mobility and

endurance. Malformation of the thorax impairs respiratory function, and odontoid hypoplasia and ligamentous laxity

cause cervical spinal instability and potentially cord compression. Other symptoms may include hearing loss, corneal

clouding, and heart valvular disease. Initial symptoms often become evident in the first five years of life. Depending on

severity of the disease, age of diagnosis will vary. The rate of incidence of MPS IVA is as yet

unconfirmed, but estimates vary between 1 in 200,000 live births to 1 in 300,000 live births.

Approximately 370 patients worldwide are currently registered in The International Morquio

Organization (IMO) survey. An estimated 1,100 patients in the developed world

have MPS VI and an estimated 3,000 patients in the developed world have MPS I.


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The MPS I RegistryThe MPS I RegistryThe MPS I RegistryThe MPS I Registry

Help Physicians Better Understand MPS I Disease by Participating in the MPS I RegistryHelp Physicians Better Understand MPS I Disease by Participating in the MPS I RegistryHelp Physicians Better Understand MPS I Disease by Participating in the MPS I RegistryHelp Physicians Better Understand MPS I Disease by Participating in the MPS I Registry

Are you looking for a way to contribute first-hand to a larger goal that may help you and other people living with MPS I disease? Ask your doctor about participating in the MPS I Registry. The MPS I Registry is an ongoing, observational database on MPS I disease. Many medical professionals agree that since MPS I disease is rare, accurate and complete information on the disease is especially important. The MPS I Registry was established in order to better understand the natural history and progression of MPS I disease. Through the MPS I Registry, healthcare providers and disease specialists can share clinical information about MPS I disease. This may ultimately contribute to earlier diagnosis, earlier intervention, and better disease management for you and other people living with MPS I disease.

Who can participate?Who can participate?Who can participate?Who can participate?

All people who have MPS I disease are eligible to participate, regardless of whether they are on disease specific treatment. Your doctor is the one who will enroll you in the MPS I Registry. He or she will explain the program and will ask you to sign an authorization form to participate in the MPS I Registry. Your participation is completely voluntary. A patient may decline to participate or withdraw consent at any time and without affecting his/her medical treatment.

What does the MPS I Registry do?What does the MPS I Registry do?What does the MPS I Registry do?What does the MPS I Registry do?

In addition to helping understand the natural history progression of MPS I disease, the MPS I Registry is designed to help physicians understand the long-term effects of treatment. The MPS I Registry is designed ultimately to provide the MPS I community with information about the MPS I disease population around the world. Data collected through the Registry and reports published using that data may be reported to regulatory authorities for a variety of purposes including information regarding the use of enzyme replacement therapy (ERT), obtaining label indications for ERT and any other appropriate regulatory purpose. The MPS I Registry is a program sponsored by BioMarin/Genzyme and administered by Genzyme Corporation. The MPS I Registry is overseen by an independent group of physicians, the MPS I Board of Advisors, with experience in researching and treating people with MPS I disease. The MPS I Board of Advisors help maintain the scientific integrity of the MPS I Registry.

Will my information be kept private?Will my information be kept private?Will my information be kept private?Will my information be kept private?

Information that your doctor submits to the MPS I Registry will reference you by patient number and initials, and not by name. Only your doctor will have access to both your name and patient number. Information submitted to the MPS I Registry will be maintained as confidential in accordance with applicable national privacy regulations and other state and local laws related to medical information.

How do I participate in the MPS I Registry?How do I participate in the MPS I Registry?How do I participate in the MPS I Registry?How do I participate in the MPS I Registry?

Before you can participate in the MPS I Registry, your doctor must call the MPS I Registry to enroll as a participating physician. Once your doctor is enrolled, you will be asked to sign a form that authorizes your medical information to be released to the MPS I Registry.

There are quite a few registries available for Lysosomal Diseases. Genzyme runs the following Gaucher, Fabry, Pompe. The There are quite a few registries available for Lysosomal Diseases. Genzyme runs the following Gaucher, Fabry, Pompe. The There are quite a few registries available for Lysosomal Diseases. Genzyme runs the following Gaucher, Fabry, Pompe. The There are quite a few registries available for Lysosomal Diseases. Genzyme runs the following Gaucher, Fabry, Pompe. The

link to being your searching is link to being your searching is link to being your searching is link to being your searching is http://www.lysosomallearning.com/support/lsd_sup_registries.asphttp://www.lysosomallearning.com/support/lsd_sup_registries.asphttp://www.lysosomallearning.com/support/lsd_sup_registries.asphttp://www.lysosomallearning.com/support/lsd_sup_registries.asp

Lysosomal RegistriesLysosomal RegistriesLysosomal RegistriesLysosomal Registries


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Data Support Commencement of LongerData Support Commencement of LongerData Support Commencement of LongerData Support Commencement of Longer----term Phase 2 Switching Study term Phase 2 Switching Study term Phase 2 Switching Study term Phase 2 Switching Study

CRANBURY, N.J., March 13, 2008 /PRNewswire via COMTEX News Network/ -- Amicus Therapeutics, a biopharmaceutical company developing small-molecule, orally administered pharmacological chaperones for the treatment of human genetic diseases, announced today that the Company will present positive results from a Phase 2 clinical study of Plicera(TM) (isofagomine tartrate) for Gaucher disease at the American College of Medical Genetics (ACMG) Annual Meeting from March 12-16 in Phoenix, AZ. Results from the fully enrolled Phase 2 trial support the previously reported interim findings that Plicera was generally safe and well tolerated at all doses and increased target enzyme activity levels in a majority of patients.

Phase 2 Plicera data presented at ACMG Phase 2 Plicera data presented at ACMG Phase 2 Plicera data presented at ACMG Phase 2 Plicera data presented at ACMG

The primary objective of this study was to evaluate safety and tolerability of different doses and dosing regimens of Plicera. The secondary objective was to evaluate certain pharmacodynamic measures of treatment, including effects on GCase (the enzyme deficient in individuals with Gaucher disease) levels in white blood cells.

Thirty patients with Gaucher disease (8 men and 22 women between the ages of 18 and 63) were enrolled, and there were 12 unique alleles represented including the most common N370S and L444P mutations. Patients were on enzyme replacement therapy (ERT) with imiglucerase for an average of 9 years prior to entering the trial, and they temporarily discontinued ERT to receive Plicera for the 4 week duration of the study.

The key findings from the The key findings from the The key findings from the The key findings from the trial were as follows:trial were as follows:trial were as follows:trial were as follows:

� Plicera was generally well-tolerated at all doses evaluated, and no serious adverse events were reported.

� GCase activity as measured in white blood cells was increased in 20 of the 26 patients with evaluable GCase data, and 5 of the 6 patients without a clear increase were either in the lowest dose cohort or the cohort dosed least frequently.

� As expected in this short term study, the levels of relevant markers of Gaucher disease including platelet counts, hemoglobin levels, glucocerebroside (substrate) levels, chitotriosidase activity and pulmonary activation-related chemokine (PARC) levels were maintained.

"These data give us great confidence in moving our Gaucher program forward," said John F. Crowley, President and CEO of Amicus Therapeutics. "In addition to a 6-month Phase 2 study in individuals naive to ERT, which is currently underway, we plan to initiate a longer-term study in individuals switching from enzyme replacement therapy to Plicera in the second half of this year."

AbAbAbAbout Gaucher Disease out Gaucher Disease out Gaucher Disease out Gaucher Disease

Gaucher disease is a Lysosomal storage disorder caused by inherited genetic mutations in the GBA gene, which result in deficient activity of the enzyme acid beta-glucosidase, also known as glucocerebrosidase (GCase). Deficient GCase activity leads to Lysosomal accumulation of glucocerebroside inside certain cells, which is believed to cause the various symptoms of Gaucher disease, including an enlarged liver and spleen, abnormally low levels of red blood cells and platelets and skeletal complications. In some cases there is significant impairment of the central nervous system.

Amicus Therapeutics Presents Positive Data from Phase 2 Clinical Trial of Amicus Therapeutics Presents Positive Data from Phase 2 Clinical Trial of Amicus Therapeutics Presents Positive Data from Phase 2 Clinical Trial of Amicus Therapeutics Presents Positive Data from Phase 2 Clinical Trial of Plicera(TM) for Gaucher DiseasePlicera(TM) for Gaucher DiseasePlicera(TM) for Gaucher DiseasePlicera(TM) for Gaucher Disease


12

The Phase 1 clinical study of recombinant human acid sphingomyelinase (rhASM) for treating ASM Deficiency

(Niemann-Pick Disease, Type B) is currently ongoing. Eight patients have completed the study to date, with

additional patients being screened and scheduled for treatment and assessment visits.

The main purpose of this Phase 1 study is to evaluate the safety of rhASM, an investigational enzyme

replacement therapy, given as a single dose to adults with ASM deficiency. During the study, known as a

sequential dose escalation study, successive groups of patients are receiving increasingly higher doses of

enzyme. The study includes five total dose groups; three have completed the study and the fourth is in

progress. Administration of rhASM has been well-tolerated in all patients to date.

More patients are needed to complete the trial, which is taking place at Mt. Sinai School of Medicine (MSSM)

in New York City. Study staff are contacting patients who may be eligible for the remaining two cohorts. The

study is open to patients worldwide who meet study’s medical requirements. Participation in the trial requires

up to four visits to MSSM. Travel expenses and study-related medical treatments are being paid for by

Genzyme Corporation, which is sponsoring the study. Anyone interested in participating may visit

www.clinicaltrials.gov (study identifier NCT00410566) for more information.

Enrollment in the Phase 1 study is expected to be completed this year, with data collection and analysis to

follow in 2009. Appreciation goes to all the patients who have participated in the study thus far, as well as to

Drs. McGovern, Wasserstein, Schuchman, and Desnick at MSSM for their ongoing work on the program.

Plans for a multi-national Phase 2 study are currently in development. Findings from the Phase 1 study will be

used to help design the Phase 2 trial. We anticipate that the Phase 2 study will be the first opportunity (of at

least two generally required for regulatory approval) to evaluate the effect of repeat dosing on various disease

symptoms over several months.

Betsy Bogard LSD Program Management Genzyme Corporation 500 Kendall Street, Cambridge, MA 02142 e-mail: [email protected] www.genzyme.com

Clinical Trial Update Clinical Trial Update Clinical Trial Update Clinical Trial Update for Neimannfor Neimannfor Neimannfor Neimann----Pick type BPick type BPick type BPick type B


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CAMBRIDGE, Mass. – Genzyme Corp. (NASDAQ: GENZ) reported today that a preliminary analysis of data from an ongoing open-label Phase 2 clinical trial of its investigational oral therapy Genz-112638 showed that the compound produced a meaningful impact on key clinical manifestations of Gaucher disease. The results highlight the potential of this compound to become an innovative treatment option for Gaucher disease.

Genzyme’s Cerezyme® (imiglucerase for injection), the standard of care for patients with Type 1 Gaucher disease, is administered through intravenous infusions. The company is developing Genz-112638, a capsule taken orally, to provide a convenient treatment alternative for patients and to provide a broader range of treatment options for physicians.

The primary analysis period of the Phase 2 study of Genz-112638 is scheduled to conclude later this year, and the results for all trial participants will be available in the first quarter of 2009. The study included 26 adults with Type 1 Gaucher disease at medical centers in North America, South America, Europe and Israel. It was designed to evaluate the efficacy, safety and pharmacokinetics of the compound over one year. Nearly all study participants had completed six months of treatment when the preliminary analysis was conducted, and approximately half of the participants had completed one year of treatment.

The preliminary analysis showed that Genz-112638 produced promising efficacy results at six months and that these results continued to improve through one year of treatment:

• At six months, spleen volumes had decreased from baseline by a mean of 27 percent among the 21 patients for whom data were available. Spleen volumes had decreased by 40 percent among 11 patients with available data at one year.

• At six months, hemoglobin levels had increased from baseline by a mean of 0.9 grams per deciliter of blood among 17 patients for whom data were available. Hemoglobin levels had increased by 1.3 grams per deciliter among 13 patients with available data at one year.

• Platelet counts increased from baseline by a mean of 18 percent among 17 patients treated for six months and by 34 percent among 13 patients with available data at one year

• Chitotriosidase levels decreased from baseline by a mean of 30 percent at six months among 20 patients and by 50 percent among 12 patients treated for one year. Chitotriosidase commonly serves as a biomarker of Gaucher disease burden, allowing physicians to monitor patient response to treatment

These preliminary results are consistent with results observed for patients beginning enzyme replacement therapy.

The analysis showed that drug-related adverse events seen in the trial occurred in a small number of patients, were mild and transient in nature, and did not require any medical intervention. The drug-related adverse events were diarrhea, abdominal pain, tachycardia, and headache.

Genzyme is currently developing protocols for two Phase 3 trials that it expects to initiate early next year. One trial is expected to include untreated Gaucher patients, and the other is expected to include patients previously treated with Cerezyme.

“We have set a very high bar in trying to develop an oral therapy for Gaucher disease given the remarkable impact that Cerezyme has had,” said David P. Meeker, M.D., Genzyme’s president of Lysosomal Storage Disorder Therapeutics. “We are excited by the potential of Genz-112638. The data we collect from this study and from the Phase 3 program will provide guidance on the roles that this compound may play in treating and maintaining patients with Gaucher disease.”

Highlight Potential of Novel Oral Compound for Gaucher Highlight Potential of Novel Oral Compound for Gaucher Highlight Potential of Novel Oral Compound for Gaucher Highlight Potential of Novel Oral Compound for Gaucher DiseaseDiseaseDiseaseDisease


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FindinFindinFindinFinding the forumsg the forumsg the forumsg the forums: : : : You can find the forums at the web address You can find the forums at the web address You can find the forums at the web address You can find the forums at the web address www.nzordforums.org.nz....

To get to the LDNZ forumsLDNZ forumsLDNZ forumsLDNZ forums, click on Lysosomal Diseases New ZealandLysosomal Diseases New ZealandLysosomal Diseases New ZealandLysosomal Diseases New Zealand.

Using the forums:Using the forums:Using the forums:Using the forums: The forums are The forums are The forums are The forums are very easy to use. There are only a few things you have to know.to use. There are only a few things you have to know.to use. There are only a few things you have to know.to use. There are only a few things you have to know.

RegisterinRegisterinRegisterinRegisteringggg To use the forum, you must To use the forum, you must To use the forum, you must To use the forum, you must register. Follow the . Follow the . Follow the . Follow the link at the forums.link at the forums.link at the forums.link at the forums.

This will take you to the Registration InformationRegistration InformationRegistration InformationRegistration Information page. Fill in the required fields and provide as much optional

information as you are happy to supply, then click the SubmitSubmitSubmitSubmit button.

The administrator will then activate your accountactivate your accountactivate your accountactivate your account, which may take a day or two. If you have troubles registering,

contact the forums administratorcontact the forums administratorcontact the forums administratorcontact the forums administrator directly at [email protected].

Once your account has been activated, you can log inlog inlog inlog in and use tuse tuse tuse the forumshe forumshe forumshe forums. To log in, enter the usernameusernameusernameusername and passwordpasswordpasswordpassword

you have selected in the boxes near the bottom of the page and click on Log inLog inLog inLog in.

Perhaps you’d like to make your first postfirst postfirst postfirst post an introduction to yourself and your family.

Following a discussion and starting new topics

ContributingContributingContributingContributing to a discussion is very easy. Simply click on the link while you are reading the discussion.

You can then add a post that will be added to the end of the discussion.

You can start a new discussionnew discussionnew discussionnew discussion by clicking on the link from anywhere inside the forum you want the

discussion to appear in. When starting a new discussion thread, you must supply a subjectsubjectsubjectsubject that lets people know the

subject of the discussion.

Join the LDNZ ForumsJoin the LDNZ ForumsJoin the LDNZ ForumsJoin the LDNZ Forums

The LDNZ forumsLDNZ forumsLDNZ forumsLDNZ forums have been up and running for a while now. However, they haven’t really taken

off. Forums could be a great resource for the group, but we need to get people signing up and

using them.

The forums can help us all stay in touch and to be informed. We can use the forums to

• Discuss Ideas Report News

• Share Ideas Or just chat

So please visit the forums, sign up and start communicating


15

Call for PostersCall for PostersCall for PostersCall for Posters for 2008 Lysosomal for 2008 Lysosomal for 2008 Lysosomal for 2008 Lysosomal Conference, ChristchurchConference, ChristchurchConference, ChristchurchConference, Christchurch

Posters and “SpeedPosters and “SpeedPosters and “SpeedPosters and “Speed----Poster” presentations: The cool new way to present your Poster” presentations: The cool new way to present your Poster” presentations: The cool new way to present your Poster” presentations: The cool new way to present your

findings in keeping with the txt agefindings in keeping with the txt agefindings in keeping with the txt agefindings in keeping with the txt age

Check out our website for more information Check out our website for more information Check out our website for more information Check out our website for more information

www.ldnz.org.nzwww.ldnz.org.nzwww.ldnz.org.nzwww.ldnz.org.nz

Traditional poster displays and speed-poster presentations are invited. “Speed Posters” will consist of a short

presentation, 2-3 minutes, introducing selected posters followed by a viewing session where delegates can view all the

posters and discuss them individually with the presenters. We welcome posters on all aspects of Lysosomal diseases We welcome posters on all aspects of Lysosomal diseases We welcome posters on all aspects of Lysosomal diseases We welcome posters on all aspects of Lysosomal diseases

including science, clinical care, and family experience.including science, clinical care, and family experience.including science, clinical care, and family experience.including science, clinical care, and family experience.

Abstracts should fit on an A4 page in Times New Roman 12 point or equivalent font and all text and diagrams and should

be submitted electronically as a Microsoft word document emailed as an attachment to Jenny Noble at

[email protected]@[email protected]@xtra.co.nz

• Title of paper should be bold and in CAPITALS.

• First name, surname & affiliation of Author(s)

• Name of presenter should be underlined.

• Affiliation should be in italics.

• Tables and diagrams may be included but the Abstract must fit on an A4 page.

LDNZ warmly invites our families to also consider submitting a poster for displayLDNZ warmly invites our families to also consider submitting a poster for displayLDNZ warmly invites our families to also consider submitting a poster for displayLDNZ warmly invites our families to also consider submitting a poster for display. The poster display is going to be a

big feature of the conference. There will be a poster viewing session where you will have the opportunity to talk about

your poster during the viewing session. Your poster may also be chosen for a short oral presentation during the speed

poster session. Please don’t hesitate to call me if you would like to discuss this further.

Don’t forget to send your

registrations to Jenny

for the Lysosomal/MPS

Conference, Christchurch


16

Please send us your feed back, your request for further information or make a donation to LDNZ .

Jenny NobleJenny NobleJenny NobleJenny Noble

16 Woodleigh Place16 Woodleigh Place16 Woodleigh Place16 Woodleigh Place

OhauitiOhauitiOhauitiOhauiti

TaurangaTaurangaTaurangaTauranga

EEEE----mail mail mail mail [email protected] [email protected] [email protected] [email protected]

Donations over $5.00 made to Lysosomal Diseases New Zealand are Tax deductible.

What happens to the funds we raise? What happens to the funds we raise? What happens to the funds we raise? What happens to the funds we raise?

� Funding of all administration expenses for our group.

� Supporting families wishing to attend Conferences.

� Advocating for families for disability support, health services and access to therapies.

� Lobbying the Ministry for improvements to diagnosis, screening and care.

� Keeping in touch with researchers and biotech companies on research progress.

� Supporting some research efforts here in New Zealand.

� Keeping you informed of progress with our mission.

Our very heartfelt thanks go to

the following organisations

who are sponsors of our 2008

Lysosomal conference

Thank you for your supportThank you for your supportThank you for your supportThank you for your support

Lysosomal Diseases New Zealand

Documents

Transcript of Lysosomal Diseases New Zealand