ACTIVATED Newsletter of Haemophilia Foundation Australian Capital Territory

PATRON December 2017 Dr Richard Pembrey AM, Newsletter MB BS, MD, FRACP, FRCPA Vol. 33 No. 4 President’s Final Report for 2017

Eventful Year remain on the Committee, and EHLs are around 1.4 to 1.7 times are joined by Committee first- that of regular factor 8 products. It has certainly been an eventful timer, Barrie Cooke. I look The story is even better for year, full of lots of highlights and forward to working with the individuals with factor 9 a couple of sad moments. On a committee to continue to deficiency. Products under trial personal front, I welcomed my advance the interests of HFACT's from a range of companies are fourth child, Matteo Raffaele members and the wider bleeding showing huge increases in half Damiani, into the world. (Ed: See disorders community in the ACT life, for some products greater page 7.) and surrounding regions. than 5 times the half-life of Life just got that little bit busier in today's "regular" factor products. the Damiani household. 2017 Conference This is phenomenal, and could Outcome of AGM There were perhaps two see a factor 9 deficient individual highlights, among many, which on prophylaxis only requiring a HFACT's Annual Meeting really stood out for me. The first is factor injection every 2-3 weeks, was held on 24th October. From just how rapidly evolving the depending on the individual. your reading of this report you women’s issues around bleeding But there are a range of other would have gathered that I disorders are. I will profess to drugs which are under nominated for, and was being on a steep learning curve development and in trial which accepted, as president of HFACT in this regard and wow, did I are far more exciting, one of for another year. Also joining me learn a lot at conference as I which I've previously written is Jenny Lees, who continues to tried to immerse myself in as about - Emicizumab. The drug is serve as Treasurer, and Rebecca many of the relevant sessions as currently in a stage 3 clinical trial Minty, who is moving from the possible. I think it is something and results to date from the trial Secretary role to the Vice the broader community is appear to be encouraging. President role. The Secretary role grappling with and embracing. Essentially, and to put it simply, it is now filled by Shauna Adams, The second issue is one I'd like to acts by binding the factor 9 and who recently joined the reflect on a little more closely factor 10 together to mimic the committee. Len Minty (my father and it relates to new treatments, missing factor 8. The drug can in law) and Julia Minty (wife) including what's on the horizon, be administered subcutaneously for bleeding disorder sufferers. (that is, it doesn't need to be This topic was the final plenary Contents injected into a vein) and only session of the conference, and I about 1/2 a millilitre per injection President’s Final Report for 2017 ...... 1 was lucky enough to have been is required. Inhibitor issues seem 2017 Conference Reports ...... 2 - 6 invited by HFA to chair this to be eliminated as well. Trials Online Resources...... 2 session. And believe me, there have found that greater than 50 Gene Therapy ...... 3 was a lot of information to take per cent of patients on weekly Phillip Bennett ...... 5 in, because, frankly, there is a lot Stephen Bennett ...... 5 dosing had zero bleeds over a 40 going on in this space. Counsellor’s Update ...... 6 week period. I should point out Please Update Your Details ...... 6 Most, if not all of us, have heard that this drug is in trial and there is Welcome Matteo Damiani ...... 7 about longer acting factor, also a way to go before it can be 2017 AGM Reports...... 7 known as Extended Half Life proven to be effective and safe. Women’s Wisdom ...... 8 (EHL). Most would know that Nevertheless, it is very Christmas Greetings ...... 8 because they have a longer half- encouraging, as are the results Dates for Your Diary ...... 8 life, those using them need to from some other drugs also under Haemophilia Contacts ...... 8 inject less frequently than they Our Mission ...... 8 would on regular factor (Continued on page 2) ACT Health Acknowledgement ...... 8 treatments. The half-life of these HAEMOPHILIA FOUNDATION AUSTRALIAN CAPITAL TERRITORY ACTIVATED President’s Report (cont.)

(Continued from page 1) More information on this is details will be provided in the presented in the article on page next newsletter. When a date for clinical trial which are also very 3. I encourage you to read it. the camp is locked in, members long acting and can be will be notified as soon after as administered subcutaneously. Coming Up In 2018 possible to lock in the dates in Looking forward, we have their calendars. Beyond these exciting commenced planning for a developments, it is fair to say that On a final note and with HFACT camp to be undertaken gene therapy seems to have Christmas and the holiday in April 2018. As per previous entered a new frontier. For years season around the corner I'll take camps, it will be heavily we have heard about gene this opportunity to wish you all a subsidized by HFACT as a means therapy being on the horizon, happy festive season. Hope to of encouraging as many people although year after year after see you in 2018. from the community to attend. hearing the same thing it would The camp will bring together seem as though that horizon was both social and educational Claude Damiani never approaching. But that sessions for the community. More President HFACT may no longer be the case. 2017 Conference Reports

Conference Abstracts and ence, Gene Therapy by Professor gate about, send an email to John Rasko AO, which is not [email protected] and we Presentations available online yet. will attempt to put you in touch Thanks to the dedicated and with someone who attended The Bennett brothers have also hard working staff at the HFA n that session. given their personal perspectives , many of the slide on attending the conference. presentations from the 2017 con- Ron Lees ference are already available in If there is a particular session that Adobe PDF format on the HFA you would like to talk to a dele- website. See the link below. These resources are very useful if you couldn’t attend the confer- ence. Although its not the same as being there, you can at least benefit from viewing the slides. They are also useful if, like me, you wanted to attend more than one concurrent session. So I look forward to reading about the session on Ageing, as I was at- tending the Improving Care Through MyABDR session in an- other room. Previous post-conference news- letters have contained extensive session reports from our dele- gates. This time we will not do a lot of that, as you can access the online resources yourself. The exception is a summary of the final presentation of the confer- ACT delegates at the 2017 conference

Abstracts and Presentations at: www.haemophilia.org.au/conferences

Page 2 December 2017 HAEMOPHILIA FOUNDATION AUSTRALIAN CAPITAL TERRITORY ACTIVATED Status of Gene Therapy in Haemophilia

Breaking news 7 December 2017 Gene therapy clinical trials cover • The endpoints, or outcomes, many areas of medicine, are well validated and easy to The Spark Therapeutics trial results presented in the session have been although the clear majority are to measure e.g. continuing and released to the media following pub- address cancer diseases (64.6%). i measurable increase in factor levels. lication in New Eng. J. of Medicine. If gene therapy is to be effective, See In the News section at the HFA there must be a method, or As a result, there have been website: www.haemophilia.org.au ‘vector’, by which the therapy is gene therapy trials in delivered into the body. Most haemophilia since 1998. Professor John Rasko AO is Director, vectors are modified viruses Cell and Molecular Therapies at Use of AAV as a Vector Royal Prince Alfred Hospital. He is which carry the gene therapy as also President-Elect, International part of their DNA sequence. An adeno-associated virus, or Society for Cellular Therapy and Other vectors include small DNA AAV, is similar to an adenovirus, a head of the Gene & Stem Cell molecules called plasmids. The common cause of illnesses of the Therapy Program, Centenary four most commonly used vectors respiratory system. However, AAV Institute, Faculty of Medicine at are Adenovirus, Retrovirus, has been found not to cause University. plasmids and Adeno-associated disease in humans. virus (AAV). i Professor Rasko gave a presentation Viruses consist of several layers. In on the current state of gene therapy the case of AAV, it consists of a in haemophilia, with particular Why Gene Therapy? genome core, in this case a reference to the Spark Therapeutics The goals for gene therapy in single strand of DNA gene therapy trial for haemophilia B. haemophilia are to 1) replace approximately 5 kilobases long (a This is a lay person’s summary of his recurrent lifelong medical presentation, from the slides. base being a nucleotide pair) interventions with a single and an outer protective protein intervention e.g. one injection; 2) Background layer called the ‘capsid’. avoid the risks of blood products, The ideal for gene therapies is a and ; 3) achieve continuous ‘living therapy’, where you are maintenance of clotting factor in given one ‘shot’ and you’re circulation. cured. This goal is a compelling, easy idea, but is hard to achieve. There are two basic strategies to achieve long term expression of There have been multiple trials of clotting factor: 1) in vivo, in which gene therapies for haemophilia the therapeutic gene is inserted with over 10 years of safety data. into the DNA of a viral vector, or; Various areas of medicine, such 2) ex-vivo in which the The theory is that by modifying as tumours, blindness and therapeutic gene is integrated the virus, replacing part of its DNA immunodeficiencies, already into stem cell therapy strand with DNA to code for have approved therapies. So, administered to the patient. ii factor IX (FIX) protein, it can be the ‘time’ for gene therapy in Haemophilia is a favoured gene used to express FIX when the AAV haemophilia is now. However, therapy target because: replicates in the liver. bringing new therapies to market • There is a wide therapeutic is constrained by regulation on In 2000, trials were carried out window i.e. even a small trials, testing and approvals. using dogs that have increase in factor expression haemophilia B. That trial was very Gene therapy trials have been can result in a significant encouraging, with the dogs taking place for longer than most outcome for someone continuing to express about 7% people realise. Since the first regarded as ‘severe’- having levels of FIX after two years. iii approved gene therapy trial in factor <1%; 1989, there has been exponential • The therapy does not require The first human phase 1/2 trial, in growth. As at August 2016, over tissue transplantation; 2001, was not as successful as the 2,300 gene therapy trials had • There are animals with trial with dogs. Although subjects received approval, with new haemophilia that can be used were expressing 11% levels of FIX approvals coming close to 200 for initial trials; two weeks after treatment, an per annum. (Continued on page 4)

December 2017 Page 3 HAEMOPHILIA FOUNDATION ACTIVATED AUSTRALIAN CAPITAL TERRITORY

(Continued from page 3) range of ages, FIX genotypes • Can gene therapy be and viral infection status. extended to paediatric immune response to AAV population and developing Most subjects did not require occurred between two and five economies.? steroid treatment. That group weeks, resulting in a destruction achieved a mean steady state There are currently ten clinical of the transduced cells and FIX expression of FIX of 31.9% ± 7.4% investigations in AAV-mediated returning to low levels. The cause between 12 and 52 weeks after gene transfer therapies in of the difference between the gene therapy. haemophilia. two trials was found to be that dogs are not normally exposed to Although two subjects were Conclusions: AAV and do not produce an treated with steroids, in fact only • Multiple trials in haemophilia B immune response to it. Humans, one showed a significant capsid and one trial in haemophilia A however are often exposed to immune response. That was have reported a single infusion AAV, so if a subject has had prior suppressed with steroids and the of vector has conferred exposure, their immune system subject went on to achieve sustained factor expression. recognises it and destroys the steady state expression of FIX of • The Spark trial, using a gene therapy. iv around 80%. vi relatively low vector dose has demonstrated a sustained Subsequent laboratory research The overall outcome of the trial mean factor IX expression of discovered that particular was a 96% reduction in mean 33.3% ± 17.8%. proteins in the AAV capsid annual bleed rates and 99% • Larger cohorts and continued caused an in vitro immune reduction in mean annual observation are needed to response. So, it was hypothesised infusion rates. Nine of the first ten confirm initial results. that if the proteins in the capsid subjects have not had treatment • Investigational AAV gene could also be modified, the since starting on the trial. vi therapies for haemophilia immune response might be Quality of life (QoL) was have been granted US FDA ameliorated or avoided. It was evaluated before starting and at Breakthrough Therapy also hypothesised that the 4, 12, 26 and 52 weeks after Designation or European immune response could be receiving gene therapy. All Medicines Agency Priority controlled through immune subjects reported improvement in Medicine (PRIME) Designation. suppressing medications, such as their haemophilia health related These are both measures to steroids. scores. vii expedite the development The Spark Trial and approval of drugs that Looking Ahead target an unmet need. The Spark Therapeutics trial, a While gene therapy trials in collaboration between If gene therapy for haemophilia is haemophilia have been a very researchers in Australia, USA and approved, how will it be encouraging success, there are Canada, has implemented this implemented? pending questions: idea. In addition to modifying • How will it be administered? • Duration of expression. It is the central part of the DNA in the Special distribution centres or now over three years since the virus to produce FIX, they have business as usual? first subjects of gene therapy also modified the DNA to create • Which regulatory agencies will trials received treatment and a ‘novel’ capsid. Additionally, be involved? over ten years in the dogs. the trial used a low dose regime,  TGA • Feasibility of re-administration and monitored liver function (ALT  Office of the Gene should it be required. and AST tests) to detect any Technology Regulator • Overcoming pre-existing immune response. • What will be the cost? neutralizing antibodies.  Adaptive reimbursement? The trial began in September • Will results be equally  Saving compared to years 2015.v Initially there were ten compelling for haemophilia A? of infusion treatment. adult volunteer subjects who • Will there be long-term or late have haemophilia B, covering a side effects? Ron Lees i The Journal of Gene Medicine ©2017 v ClinicalTrials.gov Identifier: NCT02484092 ii Mingozzi & High, Nat. Rev. Genetics 2011; 12(5):341-55. vi Spark data on file as at June 2017. iii Mount, Blood, 2002; Journal of Gene Medicine ©2002 vii Von Mackensen et. al., Poster #1100, ISTH iv Manno CS et. al. Nat Med 2006; 12(3):342-7.

Page 4 December 2017 HAEMOPHILIA FOUNDATION ACTIVATED AUSTRALIAN CAPITAL TERRITORY 2017 Conference Reports - Personal Experiences

My name is Phillip Bennett and I agnosis, information and educa- leagues or students down. One live on the South Coast at tion such as risk assessment and thing that he said that has stuck Moruya. I was very happy to genetic testing, counselling and in my mind is about fitness. The once again be given the oppor- support. This can be very useful stronger you are the less bleeds tunity to attend the 18th Australia for pregnancy and carrier test- you will have! He now has to use and New Zealand Conference ing. The concepts described in crutches to get around, but gets on Haemophilia & Rare Bleeding this session were not easy to take around his house and shed quite Disorders at the Pullman Hotel on board. Suffice to say that ge- well. Albert Park Melbourne on the netic testing will be useful for Come Saturday afternoon at the 12th to 14th October. This was couples who are thinking of start- finish, I realised that I had sat my second visit to a local confer- ing a family. I think this will be through two days of presenta- ence as previously I went to the highly relevant information for my tions and learnt more about hae- Gold Coast in 2015. The layout daughters. mophilia and more importantly and order of the Melbourne con- Being almost sixty, the session on met other people with haemo- ference was very similar to the ageing was very useful. David, philia who have had inhibitors, Gold Coast except that the Meet who has severe haemophilia with major bleeds, joint replacements and Greet area seemed some- inhibitors, told us about his life, and mental issues. Seeing others what smaller which made it diffi- and that his bleeds were not very who have conquered life with cult to move around. However, it well controlled. The impact haemophilia has encouraged made it easy to meet and catch stopped him seeking medical me to look after my body better up with people that I had not attention which resulted in sub- and to exercise more. seen for a long time. stantial joint damage over time. Roll on Sydney 2019! I have two daughters who live in However, he was able to com- , and I was particularly plete university and work for Cheers, interested in the session Family CSIRO in a teaching role. He felt Planning and the Role of the Ge- guilt in that when he couldn’t Phillip Bennett netic Counsellor. The genetic work because of his haemophil- counsellor can offer genetic di- ia, he was letting his work col-

I was fortunate enough to attend Happier Family by Dr Justin cise, the fitter you are the less the 18th Australia and New Zea- Coulsen was excellent (he has six bleeds you will have, and sec- land Conference on Haemophil- children!), he made a tricky sub- ondly, he got older and wiser ia & Rare Bleeding Disorders at ject funny and very interesting. and now bleeds are few and far the Pullman Hotel Albert Park He spoke about having a family between. Melbourne on the 12th to 14th plan, how LOVE is spelled TIME, I attended the Women and Tell- October. This was my first visit to about limits for children and the ing Others session on Saturday a local conference as previously importance of laughter in family afternoon. I wanted to get a fe- I’ve only been to the World Fed- relationships. male viewpoint on haemophilia. eration of Hemophilia confer- Being an older man myself, an- The first part was about the diffi- ence that was held in Melbourne other interesting presentation culties that families with haemo- in 2014, which was very large was about ageing with haemo- philia have when trying to get with something like 5000 people philia. David, who has severe and claim on disability and travel attending from all over the world. haemophilia with inhibitors told insurance was very informative. However, the local one only had us about his life with haemophil- But, it was the personal stories by a few hundred people attend. ia, and the substantial joint dam- two women who have So it was a real nice and cosy age in his ankles, knees and el- vWD/haemophilia that I found conference, and it was good to bows. For many years be was a really interesting. The first was meet with other people with teacher, and when he couldn’t Sharron who has vWD who ex- haemophilia, and hear their sto- work he felt that it was unfair on plained about growing up and ries. his work colleagues or students. being ‘wrapped up in cotton All the sessions were excellent, He gave two important con- wool’. Her mother told her school but the first one 21 Days To a cepts; the importance of exer- (Continued on page 6)

December 2017 Page 5 HAEMOPHILIA FOUNDATION ACTIVATED AUSTRALIAN CAPITAL TERRITORY 2017 Conference Reports - Personal Experiences (continued)

(Continued from page 5) with, vWD and haemophilia. a female point of view. This ses- Second story: Susie who also has sion really showed the problems teachers, so that everyone knew. vWD worked in a large office, that women have with haemo- Later when she got married tell- and one day fell down the stairs. philia and vWD and shows quite ing her husband was going to be She couldn’t move and the am- strongly that haemophilia is not risky but someone else had al- bulance was called. Her work- just a ‘boys’ sickness. ready told him! Always went to mates helped her work through When the conference finished on the Alfred hospital for treatment what happened. Later her boss Saturday it was sad to leave, but and had three children. She (first aid officer) asked about her I‘m hoping to go to the next Aus- stressed that it is very important condition and she was able to tralian and New Zealand confer- to have a haemophilia plan for reveal her vWD. She never felt ence in 2019. the birth of each of her children, discriminated or judged. She and also for any surgery. Also, aims to be her own best advo- Kind regards, that women are the glue that cate! This was a good session for holds a family together, and if me to attend as my mother bruis- Stephen Bennett she is not well then the whole es very easily and almost certain- family suffers. Now she is and ad- ly will have haemophilia. I also vocate for women with, or living wanted to see haemophilia from

Christmas Greeting from Your HFACT Counsellor

I would like to say thank you to tional material on bleeding dis- In 2018 I will have new working all members of the Haemophilia orders, on building happy fami- hours, I will be working at The Foundation in the ACT and near lies, on pain management, infor- Canberra Hospital at The Hae- regions for my very rewarding mation about self-care courses, mophilia Treatment Centre on work with you in 2017. for assistance with getting into Thursdays between 10am and university and staying at universi- 2pm, and by private appoint- About My Role ty after extended sick leave. I ment. I can be contacted on My role is one of connecting. don’t have all the answers but 0409 830 472 or via email to This last year I met many of you I’m happy to find out what can [email protected] , in social settings, at work, in hos- be done to support you. Have a safe and happy Christ- pital, in cafes and in your In 2018 get in touch about how I mas, homes. can assist you and your family to Best Regards, For those who don’t contact be your best ever. me, I am a free resource; some- one who can provide educa- Working Hours in 2018 Kathryn

Please Update Your Contact Details

HFACT has recently been receiv- out of date or disconnected. teers, and there many demands ing returned newsletters and oth- on our time. While it is often possible to locate er mail or emails for members a member through other means, If your details have changed, or whose contact details are out of sometimes there is no alternative change in the future (especially date on our database. to removing that person or family home phone numbers that During the organisation of several from our contact list. change due to the NBN rollout) events during the year, volun- please inform us. Contact a It is also a time consuming pro- teers rang members to inform committee member, tell Kathryn cess to track people down. All them of the event and promote Body or provide the details online administrative functions of HFACT participation. In many cases we at www.hfact.org.au/update are carried out by unpaid volun- found phone numbers that were

Page 6 December 2017 HAEMOPHILIA FOUNDATION AUSTRALIAN CAPITAL TERRITORY ACTIVATED Matteo Raffaele Damiani

Welcome nostra fame! As it happens, there is in fact a fugitive Sicilian Mafia The Minty/Damiani family boss by the name of Matteo increased its membership by one Messina Denaro who is ranked on 2 September with the birth of by Forbes magazine as among Matteo Raffaele. Perhaps the ten most wanted criminals in determined to be a Spring the world... Just as well Matteo arrival, he came a week late Raffaele has two older brothers and weighed a healthy 3.79kg and a sister to keep him in line! and 51cm long. Matteo is long-time members’ Like his older brothers, he also Len and Marylou Minty’s sixth has haemophilia - prompting a grandchild. tongue-in-cheek comment at the recent multidisciplinary haemophilia clinic that the Julia Minty Damiani’s could perhaps come to be known as “The Family” - though hopefully not of Cosa

AGM Report

2018 Committee awards by the committee at the subscription fees, making just one 2017 conference. class (previously two) of financial The Annual General Meeting in member for an annual fee deter- October elected a new commit- Subscription Fees mined by the committee. Fees tee for 2018, as follows: Finally the AGM voted to change for 2017/18 onward are now $20, President: Claude Damiani our rules of association, as ad- including GST. Vice-president: Rebecca Minty vised in the notice of the AGM. Treasurer: Jenny Lees The change varied the annual Secretary: Shauna Adams General committee members: Barrie Cooke, Ron Lees, Julia Minty and Len Minty. Reports Available Online The President’s report and the Financial reports for 2016/17 are available on our website. See www.hfact.org.au/publications/ annual-reports Life Membership Award The AGM also awarded Maria Wensing honorary life member- ship for her services to the foun- dation since 1984. Fred Wensing was previously awarded life membership. They were not awarded at the same time as our rules of association only permits one award per annum. However, both Fred and Maria were pre- sented with certificates for their Fred and Maria Wensing are presented with certificates by Claude Damiani.

December 2017 Page 7 HAEMOPHILIA FOUNDATION AUSTRALIAN CAPITAL TERRITORY ACTIVATED Women’s Wisdom

The final Women’s Wisdom get the youth session and von Wil- We will put together a plan for together for 2017 was held on lebrand disorder, and Jenny on 2018 early in the new year and Sunday afternoon the 26th No- the latest news on gene therapy suggestions for topics and ven- vember. A group of us got to- for haemophilia. There was good ues for Women’s Wisdom are al- gether to hear about the recent discussion about the topics and ways welcome. You can con- Haemophilia and Rare Bleeding we all enjoyed a wonderful after- tact Marylou at Disorders conference. Kathryn noon tea. Thank you to Julia for [email protected] spoke about a session on insur- hosting the afternoon and ance and disclosure, Shauna on Marylou for organising us all. Jenny

The HFACT Committee wishes all members, people who have a bleeding disorder, their families and our caring health professionals a merry Christmas, a happy New Year and a safe and prosperous 2018.

Dates For Your Diary

Tuesday, December 12th 7.30pm HFACT Committee meeting, Woden Southern Cross Club. Dinner 6.30pm Friday, April 27th 2018 Canberra Hospital HTC Multidisciplinary Review Clinic May 20th - 24th 2018 XXXIII WFH 2018 World Congress, Glasgow, Scotland Haemophilia Contact Details

Canberra Hospital Haemophilia Foundation ACT Main Switchboard: 6244 2222 President: 0412 839 135 Web site: [email protected] www.canberrahospital.act.gov.au Counsellor: 0409 830 472 [email protected] Haemophilia Treatment Centre: Secretary: [email protected] Mon to Fri 9am - 5pm: 0481 013 323 Treasurer: [email protected] Via email: [email protected] Web site: www.hfact.org.au Physiotherapy: 6244 2154 Haemophilia Foundation Australia Paediatric Day Stay Centre: 6174 7372 Office: (03) 9885 7800 or free call 1800 807 173 Web site: www.haemophilia.org.au

Our Mission Acknowledgement “To improve the wellbeing of the haemophilia community Haemophilia Foundation ACT through mutual support, networking, advocacy and striving acknowledges that our newsletter has been produced with the fi- for optimal health care.” nancial support of ACT Health.

This newsletter is printed on 100% recycled HAEMOPHILIA FOUNDATION PO Box 331 paper, carbon neutral if possible. Contact AUSTRALIAN CAPITAL MAWSON ACT 2607 us if you would prefer to save paper and TERRITORY postage by receiving the electronic version via email.

Page 8 December 2017