Allyson Lock opened the conference and thanked everyone for coming. She introduced the committee members and the process that had been gone through to make it all happen.
Atendees included the patients and their family, pharmaceutical companies investing in new therapies and producing current enzyme replacement therapies (ERT), and top researchers in the field from USA and Australia, along with support organisations such as NZORD. It might be best to wait till we have permission to use the presentations then we could include the photos, presentations and a brief blurb and create a conference page on the website? Although not sure how easy it is to add links through the website to the presentations? I think it would be best to wait until we have the permissions, then we can send an email out to everyone saying the presentations are available on our site to download or can be sent out, but obviously not all presentations at once. I’m not sure about adding links to documents on a website either. I can try on my website and see how to do it if you like?
Dr Collette Bromhead The first speaker was Dr Collette Bromhead, CEO of NZORD, who talked about the work that NZORD does and how it works with patients for positive outcomes. Dr Bromhead stated that NZ has the highest density of registered charities in the western world, so everyone is competing for funding. Just some of NZORD’s outputs include; advocacy and profile raising with the Ministry of Health/PHARMAC/external stakeholders, hosting websites for 40 support groups, responding to patient and clinician enquiries and maintaining a specialist database. She also spoke about the briefing that was produced for the incoming Minister of Health and gave a breakdown on the medicines funded under the rare umbrella by PHARMAC, noting that the trial by PHARMAC for funding rare diseases had truly been a failure. Next up was the bombshell that funding from the government for the organization could be cut by June 2018 which will impact hugely on NZORDs ability to help the rare disease community. The plans of what NZORD intends to do if funding is secured were laid out and included: - Greater coordination for support groups and patient get togethers - Offering web tools such as video conferencing to facilitate small groups to get together - Expanding the Specialists’ Database to allied health practitioners - Continuing to drive the agenda with Government around equitable access to rare disease medicines, a rare disease register - Facilitating and coordinating research and clinical trials using patient-driven databases - Hosting a site for NZ researchers on NZORD website to enhance collaboration Dr Bromhead also focused on the NZORD Rare Disease Day symposium and poster child campaign which was designed to raise awareness of rare diseases for GPs, nurses and researchers. A request for stories from the rare disease community was made to enable the collective voice to be heard through sharing real people’s challenges and triumphs. This ‘stories project’ can give the public and politicians insights into the real issues that are faced over and over again. The message that “together we are strong” must mean speaking up and coming together to raise the voice of the rare community enough so that decision makers can hear us!
Dr Barry Byrne Dr Barry Byrne from the University of Florida gave a great talk on current research and newborn screening for Pompe disease. Information included brain involvement through accumulation of glycogen in the brain, which consequently causes damage to neurones. He emphasised that early treatment was vital to long-term positive outcomes. Interestingly, Dr Byrne stated that oestrogen appears to be protective to neurone loss. Dr Byrne spoke about the newborn screening program in America and how they have looked to the successful model that has been run in Taiwan. This is of interest to us here in New Zealand as we are focusing on getting Pompe disease added to the newborn screening panel here. Diagnosis of Pompe includes establishing low functional GAA enzyme levels and genotyping to rule out pseudo deficiency, identify carriers, predict infantile-onset versus late-onset, and predict Cross-Reacting Immunologic material (CRIM) status. The current treatment is enzyme replacement therapy (ERT) that is initiated as soon as possible, and early initiation of ERT improves intermediate term outcomes. Taiwan currently screens for Pompe disease and both Washington State and Missouri are doing pilot studies on Pompe screening. Taiwan has screened 470,000 infants for Pompe and 10 infants have been identified by the screening and started early treatment. Washington has identified 4 infants with Pompe, 4 carriers, 3 carrier/pseudo deficiency, and 6 heterozygous for pseudo deficiency. Missouri has screen 43,701 samples with 27 identified to have some type of LSD, 18 screened positive for Pompe, and 8 identified with Pompe (3 infantile, 3 late-onset, and 2 of unknown significance).
Laura Byrne Laura provided a briefing on the benefits of nutrition and exercise in Pompe patients. She used videos of patients undertaking different exercises that were created specifically for Pompe patients. She also stressed the dangers of over-exercising, as Pompe patients need to maintain some muscle resistance to retain the ability to stay mobile. Laura spoke about the importance of a low carbohydrate diet and sub-maximal exercise, as much as you can when you have Pompe. She screened some slides of various exercises that mobile Pompe patients can do. There are exercises on the web that wheelchair bound people can do. Laura talked on Pilates being positive, but Yoga stretches the ligaments too much which is bad since we don’t have the muscles to hold everything together and it causes over extension.
Freda Evans Freda talked about her journey from being diagnosed almost 30 years ago, to finally getting access to treatment. Her touching story prompted members of the audience to also add their own stories into the mix. Freda was given the gift of Myozyme through Genzyme/Sanofi’s compassionate access program in 2017. This followed years of requests for treatment being denied by PHARMAC.
Ronelle Baker Chief Executive of Muscular Dystrophy Association of New Zealand shared insights, information and made a plea for collaboration within all communities affected by rare diseases to connect and work together for better outcomes for all. She touched on the future focus of MDANZ and the desire for collaboration and community leadership across multiple organizations moving forward. MDANZ offer amazing support and research within the field of muscular dystrophy. Ronelle discussed the changes that have occurred in their organization in the past year. Things like amending their Vision to “Freedom beyond limits” the Mission to “promoting freedom of choice in a responsive society” to make them simpler to understand. It is estimated that 4,500 New Zealanders have a neuromuscular condition. MDA supports patients with nearly 60 different conditions of which some are very rare. She outlined the conditions they cover and the prevalence of each.
Dianne Webster Dr Webster spoke on the process and pitfalls that will be encountered when trying to have Pompe Disease included in the Newborn Screening program. She outlined the current screening process and the fact that the purpose of screening is to achieve health gains. If systems are not in place to add benefit to the patient after diagnosis then is there actually any benefit achieved? Questions were raised as to what may come from early diagnosis or if people were carriers, would that create false positives? Dr Diane Webster, clinical scientist at LabPLUS at Auckland DHB spoke about new-born screening and the complexities of ethics when considering the addition of a new rare disorder to newborn screening. The process and policy framework of adding conditions to newborn screening was explained which involves a wide range of information being considered including looking at what other counties are doing. Questions include: Is there a better way to do this? Just because we can screen, do we? Does testing need to occur before symptoms develop or just once symptoms develop? Is there an effective treatment available that works? This process then follows a framework through a governance group (including a technical group) and national screening advisory committee to allow decisions based on overall health gains with the focus of getting more benefit than harm for the population. Pompe patients can fill out a new disorders form which will initiate this process and were encouraged to do so. Dr Webster explained that screening can lead to positives when the person would not go on to get the full disease and this can cause avoidable mental distress. Other ethics relate to the right to know for the child and that when an identified family have a second baby genetic testing is not always done as it is not to the babies’ benefit. Other factors mentioned included mass screening versus diagnostic screening, and only offering screening for family studies with a known patient, along with a focus on increasing clinical awareness for differential diagnosis rather than screening. This raises emotive issues as once symptoms develop the child has potentially already suffered irreversible damage and ERT or gene therapy benefits may be limited. Dianne played devil’s advocate about newborn screening. Was it a good thing? Would it change the way parents treat children with LOPD who may not develop symptoms until their later years?
A question I have is, if there is no known history, as there usually isn’t with an autosomal recessive disorder, would screening be done if it was only offered for people with a known history of the disease? If no, then we will miss the people with Pompe disease.
Raymond Saich The president of the Pompe Association in Australia Raymond Saich lobbied Federal Government to place Myozyme for Pompe disease on the Pharmaceutical benefits scheme. He was awarded a Medal of the Order of Australia in the Queen’s Birthday honours list for this work. Raymond explained how his “pleasantly persistent” campaign to the Australian Federal Government eventually led to success for Pompe patients. He was able to locate champions within government who cared for this issue and create momentum with 136 minister letters, 30 articles in the media, print or on TV and two speeches made in parliament. The huge difference to New Zealand is that they have politicians who are willing to support patients. Raymond said they had to fight perceptions that it was an old person’s disease. So all meetings with politicians were conducted using a team of three people, one being a young patient or mother so that the clarity of how this disease affects the range of ages was understood and appreciated. Myozyme is available in 76 countries, however in New Zealand this drug is not available to adult patients although it is funded for new-borns with Infantile Onset Pompe Disease (IOPD). Currently there are no babies in NZ with this disease, and no new-born screening. Without screening for early diagnosis and subsequent treatment, the outcome is gloomy for any clinically identified babies as by the time symptoms are identified and the system of diagnosis has run its course vital treatment time is lost and the infant would be likely to die before diagnoses.
Miriam Rodrigues Miriam provided an overview of the NZ Neuro Muscular Disease Registry which has a primary aim of enabling participation in research, including clinical trials and natural history studies, and a secondary aim of obtaining molecular confirmation of diagnoses. She gave an indication of the numbers of people involved and that they were spread across the country. It was stated that many people diagnosed with Limb Girdle Muscular Dystrophy probably actually have Pompe disease as only 14 out of 59 people have a molecular diagnosis for LGMD. The future direction for the registry is to facilitate diagnosis, continue to contribute data to natural history and feasibility studies, assist in recruitment for trials and studies, and advise researchers. Miriam spoke about the Neuromuscular Disease Registry and she urged all Pompe people to sign up with it so that we can gain a better understanding of our needs.
Annelise La Roche Annelise is the Business Manager for ResMed. She spoke on the benefits that may be available for patients using the sipper machine. She demonstrated all of the functions and options available and then made herself available for people to see the machine in action.
Anthony briefed the audience on the Sanofi Genzyme Humanitarian Programs around the world and how it has provided a lifesaving stopgap between patients being diagnosed and an established patient care support system being implemented in their country. It is a program that can serve patients for short term or long term depending on the individual’s requirements. It has been going for over 25 years and there are no plans to stop it. They are currently supporting over 700 patients around the world with Gaucher, Fabry, Pompe, MPS I and MPS II with plans to include ASMD. Anthony talked about bringing expensive drugs to people in countries where they are not funded. This also applies to New Zealand as 4 Pompe patients were given the gift of Myozyme because of lack of funding by successive governments over the years.
Michelle Hackenberry Michelle spoke on Data Registry Services whose mission is to enhance patient, physician, and pharmaceutical comprehension of disease and associated treatments through increased data precision and patient participation in medical data registries. The registry is supported by Sanofi Genzyme and participants are provided free access to all of their medical records, which is particularly useful for people who are travelling and require access to their information in an emergency. The registry stores the details of patients with Pompe, Gaucher, Fabry or MPS on a voluntary basis. This registry collects information along a similar line as the Neuromuscular registry in NZ but this one is specifically for Pompe. Work is being done so that NZ patients can join the registry at Data Registry Services.
Anthony Earp 2 Anthony returned to the lectern to explain the process for bringing a rare disease drug to the patient. He covered some of the difficulties faced; even working out what is a rare disease is, is different all around the world. In New Zealand there isn’t an official definition of what is rare. Drug companies do deals with governments to obtain market exclusivity. This exclusivity can vary from country to country and vary in duration. Advances in technology have encouraged more companies to pursue rare disease treatments in the past decade. Since many rare diseases have a genetic component or cause, greater knowledge in this area is progressing therapies significantly. Some of the challenges that arise are the small number of people available for studies/trials, a sick and deteriorating patient population, the length of time to achieve a measurable effect, and diversity in regulations across different jurisdictions. There are also a lot of specific paediatric challenges as often the gene effect is the same in children as in adults however the effect of the disease on children can be much more severe, so treatment needs to be initiated early in order to prevent irreversible end-organ damage. Genzyme has invested more than $1billion in manufacturing facilities around the world as manufacturing ERTs is a highly complex, resource-intensive and time-consuming endeavour.
Barry Byrne 2 Dr Byrne discussed the difference between ERTs and Gene Therapy and the possible way ahead for treatment of Pompe disease A gene therapy that treats respiratory problems in early-onset Pompe disease was shown to be safe during its first human trials. The therapy uses a harmless adeno-associated virus to deliver a functional copy of the affected gene to muscle cells in the diaphragm of patients who have respiratory troubles. Nine patients completed a trial that found the therapy agent produced no adverse effects and improved respiratory function in the study participants. The safety finding follows earlier publications by UF Health researchers that established their gene therapy’s effectiveness: Breathing function improved in a group of nine patients when compared with participants whose treatment involved breathing exercises. Dr Byrne said the gene therapy represents a significant advance over enzyme replacement therapy, which involves regular intravenous infusions that contain the needed enzyme. While the enzyme treatment can reduce symptoms and prevent long-term damage, it is expensive and does not address the neurological aspects of Pompe disease. Current enzyme replacement treatments cannot cross the blood-brain barrier. Restoring gene function in neurons, or nerve cells, is particularly important because it affects muscle cell functioning and signalling. We know the gene therapy vector — when given systemically — actually enters the brain and corrects neurons that have the same deficits as muscle cells in Pompe disease. In the recent study, patients were assigned to two dosing groups and treated with different amounts of the gene therapy. Neither group suffered any adverse reactions that were attributed to the therapy. One issue that will continue to be studied is the gene therapy’s durability. Byrne said a child’s growth will likely reduce the effect of the treatment, meaning that it could last five to 10 years in school-age children and probably less if given to an infant, unless there is a provision for later exposure to the therapy. Next, researchers will begin work on a trial to test the gene therapy systemically by administering it intravenously. The National Institutes of Health has provided a three-year grant and patient enrolment should begin shortly. By giving the treatment intravenously, researchers expect to treat most of the disease-affected tissues, including neural tissues, the heart, the diaphragm and the peripheral muscles. They also will use immunosuppressive drugs that prevent potential reactions to the treatment and would allow for repeat administration in the future. That approach will address the limited durability of the treatment, researchers said. The study will be conducted with collaborators at the NIH.
Chelsea Karbocus and Doug Laidlaw Chelsea and Doug came from the USA and introduced the audience to Audentes Therapeutics and the therapies they are currently working on developing. They have multiple products in development, targeting diseases that have little or no treatment options currently. It is hoped that human trials will be starting in 2019 for gene therapy for Pompe disease. Chelsea discussed the patient advocacy policies and explained that integration of the patient and family perspective is at the core of their work. Doug provided an overview on how a gene therapy approach works and how they are attempting to create treatments using a virus to deliver functional genes to the body.