HAE in Israel - 2016 Patient Management & Healthcare Issues - PowerPoint PPT Presentation

World Allergy Organization Scientific Congress Jerusalem, December 6-9 2016 HAE in Israel - 2016 Patient Management & Healthcare Issues Avner Reshef MD, Iris Leibovich-Nassi RN, MA, PhD student Angioedema Research Center, The Sheba Medical Center, Tel Hashomer, ISRAEL

Hereditary Angioedema (HAE) in Israel Chronic life-time, debilitating disease, characterised by relapsing attacks of swelling in different body organs, occurring in an unpredicted manner Rare disease with global prevalence of 1:50,000 Approximately 180 patients have been diagnosed in Israel (pop. 8,500,000) Calculated prevalence of HAE is therefore 1: 47,200 We estimate that only 65-70% of adults and children have been so far correctly diagnosed No estimates available for the Palestinian population (WB & Gaza)

Israel HAE Specialty Centers Independent state from 1948 (68) Area: 22,072 Sq Km (59% desert land) Total population 8,500,000 (2015) Major HAE Specialty Centers : 1. Sheba Medical Center (Tel-Hashomer) 2. Sourasky Medial Center (Tel-Aviv) 3. Bnay-Zion Medical Center (Haifa) All HAE centers are actively involved in clinical research Most patients are managed by Allergists/Immunologists and HMO GPs’ EDEMA Israel patient organization

Drugs for Orphan diseases The NIH classifies 7,000 disorders as “orphan diseases” and estimates that 25 million people are globally affected Orphan diseases are classified in the US as diagnosed in <200,000 patients and in the EC as fewer than 5 cases/10,000 Drug development for orphan diseases is one of the major investment trends in the world pharmaceutical industry Modern treatment of HAE incurs considerable economic burden on health expenditures of individuals and on national health systems Before self-administration era, emergency department and hospital costs accounted for 2/3 of costs for patients with severe attacks http://seekingalpha.com/author/smith-on-stocks/articles

Consensus on Treatment of Acute HAE attacks* 1. All patients should have access to at least one of the effective medicines for treatment of acute attacks-“on-demand” 2. Whenever possible, patients should have on-demand medicines at home, sufficient to treat two separate attacks 3. Ideally, patients should be trained to self-administer so that attacks can be treated early 4. All attacks, irrespective of location, are eligible for treatment as soon as they are clearly recognized by the patient, ideally before visible or disabling symptoms develop 5. Patients should immediately report to the hospital if laryngeal symptoms persist following an initial treatment * Cicardi M et aI. International Expert Consensus (HAWK), Allergy 2012; 67: 147–157

Israeli Health-care System Medical insurance is compulsory and provided to all the citizens (1994) Health services are provided by 4 certified HMO’s ("Sick funds"), financed by the taxpayers (Health Tax 3.1-4.8% of individuals’ gross income). "Basic Health Basket“ - All citizens are entitled to obligatory benefit package: GPs’, specialists, para-meds, prescriptions, ER visits, hospitalization, Lab, medical equipment, Imaging, Rehabilitation Supplementary health insurance programs (additional coverage) are offered by the HMO’s for extra fee, including a broader range of services Private Medical Insurance are offered to whoever can afford them. Insurance policies have a wide range of additional benefits, services and options, including medications and procedures not included in the basic “health basket”.

Extended Health Basket (EHB) Principles Israel declare that it aspires to keep up with the advancements of modern medicine, provide health services and infrastructure oriented to society needs, and to supply the needs of all its citizens "Extended health basket” (EHB)- subsidize (co-pay) new, expensive drugs and advanced medical technologies, not covered by “basic health Basket” Most budget goes for cancer, biologicals and rare genetic disorders The law allows to update and expand the health basket from time to time, according to pharmacologic and technologic advancements in medicine A public committee is convening each year to decide, based on professional opinions and EBM principles, which drugs and technologies will be added This year >700 drugs & technologies compete on 550 miILS budget (130 miUSD) http://www.health.gov.il/Services/Committee/vsal/Pages/default.aspx, http://www.moia.gov.il/Publications/health_en.pdf

Present HAE Situation in Israel  Fou r new HAE drugs has been introduced into the EHB since 2010: Three C1-INH concentrates : Berinert, Cinryze, Ruconest 1. Bradykinin-receptor blocker: Firazyr- icatibant 2.  Current drugs are only indicated for on-demand treatment  Regulatory approval was recently received for IV self-administration  Following the recent registration of Berinert for STP , we are lobbying the inclusion of ‘ Berinert pre-procedural’ in the EHB , hoping to provide it for all Israeli patients  We are focusing our efforts on training patients for self-treatment , which should reduce dependence on health resources (i.e. recent results of SC Berinert prophylaxis study)  We strive to get all HAE experts in Israel and region to collaborate and work together

Doctoral Thesis The Relationship Between Premonitory Signs and Symptoms (Prodromes) and Onset of HAE Attacks Iris Leibovich 1.2 , Hava Golander 2 , Raz Somech 3 , Avner Reshef 1 1 Angioedema Center, Sheba Medical Center, Tel- Hashomer, 2 Department of Nursing, Sackler School of Medicine, 3 Safra Pediatric Hospital, Tel-Hashomer; Affiliated to the University of Tel Aviv, Israel  Aimed to study the association between prodromes and attacks of HAE  Collecting prospective data on HAE attacks: severity, form, location, duration, organ dysfunction, drug usage etc.  Secondary outcomes will include QoL parameter evaluating patients’ perception regarding signs and symptoms preceding the attacks  Preliminary study, Retrospective phase, Prospective phase

Methods  The study is designed to include all HAE patients in Israel  HAE-specific questionnaire was constructed and refined, based on previous instruments used by our group and others  So far 130 patients (43 men, 57 women, mean age 36 years, range 1-69) have been screened  Future data (prospective) will include: disease course, burden of disease , utilization of health-system resources , patients' experience with prodromes , and whether they can predict an oncoming attack

Patients Screened - Oct 2016* Angioedema Age Children Children No. Range M/F Type (M±SD) (<18) Age (M±SD) 11.13 ± 4.3 HAE I & II 130 36 ±20.5 1-69 43/57 33 (Range 1-17) Canada 2 2 Syria 11112 2 2 Algier 2 2 4 5 Countries of origin: Azerbijan Egypt Morocco Tangier 103 Ukraine USA Turkey Romania France Russia Israel *Data collected from Sheba (Dr. Reshef) Sourasky (Prof. Kivity) Bnay Zion (Prof. Toubi), Ha’emek (Prof. Rottem) Medical Centers

Association between prodromes and attacks (N=81) Having a prodrome before attacks Can predict oncoming attack based on Prodrome 6.7 6.7 7.1 20.2 28.6 Always 28.6 Absolutely Frequently Usually 66.6 Rarely Sometimes Never 35.7 No Having a prodrome without attack 0 7.1 28.6 Always Frequently Rarely 64.3 Never

Sheba Angioedema Research Center- 2016 Child Angioedema Age No. Range M/F Fam Child* Age Type (M) (M) 36 9.13 Type I & II 106 32.0 1-71 51/55 40 (M/F 18/18) (1-17) Type III 44 37.4 18-59 1/44 25 - - AAE 11** 66.8 37-80 7/4 11 - - ACE-I 25*** 71.8 51-87 14/11 25 - - Total 186 52 1-87 72/114 89 36 - * <18, **3 deceased, *** Acute Sheba ER cases

Future Trends in HAE Drug Development 1. Advocating patient autonomy => home treatment, self administration 2. Additional formulations for long-term prophylaxis 3. Switching C1-INH therapy from IV to SC route (Berinert, Cinryze RTU) 4. Drugs for Oral administration (Avoralstat, APeX-1) 5. Novel kinin-cascade inhibitors (Lanadelumab, APeX-1, anti PKK, anti FXII-3F7) 6. Future cost of new drugs is predicted to be still very high 7. Special insurance plans and government-supported co-pay programs will be required

Special thanks to CSL-Behring, Marburg, Germany for hosting this mini-conference Angioedema Research Center Sheba Medical Center, Tel-Hashomer Affiliated to Tel-Aviv University, Israel