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Market Access Overview in Hemophilia: Challenges and Opportunities


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An overview of the disease, total patient populations in major hemophilia affected nations, treatments (current and alternatives) and future outlook

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Market Access Overview in Hemophilia: Challenges and Opportunities

  1. 1. Market Access Overview in Hemophilia Challenges and Opportunities An overview of the disease, total patient populations in major hemophilia affected nations, treatments (current and alternatives) and future outlook ©Niteo Partners Consulting 2015 1
  2. 2. Contents ©Niteo Partners Consulting 2015 2
  3. 3. Executive Summary • Hemophilia is almost always inherited and caused due to mutations in the X chromosome and therefore referred to as an X-linked disorder • Patient population: More than 56% of the patient population remains unidentified o Estimated worldwide : 400,000 o Identified patients : 176,730 o US, India, Brazil and China are the major markets of Hemophilia in terms of patient population • Currently available treatment options: Replacement therapy, ITI therapy and Gene Therapy (advancements have been made in this therapy area) • The cost of Hemophilia varies significantly according to the age and life span of the patient • Despite the extremely high costs, investments in gene therapy continue to grow and a genetic cure for hemophilia no longer seems a distant possibility • Long-acting recombinants, which have a considerably longer half-life period are about to enter markets this year and could capture considerable market share • The new treatments, especially gene therapy, look increasingly promising in trial phases and could significantly change the treatment paradigm in years ahead. However, access to new and existing therapies still remain highly restricted in most major markets ©Niteo Partners Consulting 2015 3
  4. 4. INTRODUCTION: HEMOPHILIA ©Niteo Partners Consulting 2015 4
  5. 5. Introduction: Hemophilia • Hemophilia: A rare inherited bleeding disorder in which the ability of the body to form a clot during haemorrhage is severely compromised • This is attributed to a deficiency in clotting proteins (clotting factors) in the blood • Hemophilia is genetically caused due to mutations in the X chromosome and is much more common in males • In acquired Hemophilia, the body produces antibodies (known as inhibitors) that attack clotting factors, most often factorVIII. It is extremely rare and classified as type unknown • Three main types of Hemophilia ©Niteo Partners Consulting 2015 5 A B C
  6. 6. Diagnosis • Hemophilia is diagnosed primarily by reviewing a patients family medical history as it is an inherited condition • Physical examinations and blood tests help determine the extent and severity of the condition • People with known histories of the disease can have tests done during pregnancy to determine if the fetus has inherited the condition. However, these may pose a threat to the fetus • Hemophilia cases are generally diagnosed between 0-2 years after birth with the mean age for diagnosis being 9 months[1] • Blood clotting factor tests help to characterize the type and severity of the hemophilia condition ©Niteo Partners Consulting 2015 6 Severity Levels of factor VIII or IX No Hemophilia 50-100% Mild Hemophilia Between 5% and 50% Moderate Hemophilia Between 1% and 5% Severe Hemophilia Less than 1%
  7. 7. Prenatal and Postnatal Diagnostics ©Niteo Partners Consulting 2015 7
  8. 8. TOTAL PATIENT POPULATION – HEMOPHILIA WORLDWIDE Year 2013 ©Niteo Partners Consulting 2015 8
  9. 9. Facts and figures • Estimated occurrence of the various types of Hemophilia in the United States (US) ©Niteo Partners Consulting 2015 9 Estimated to occur once in 5,000 live male births in US One in 20,000 live male births in US Extremely rare with an estimated one in 100,000 cases in the US A B C
  10. 10. Unidentified Patient Population • Comparing this total with the estimated figure of 400,000 based on the probability of occurrence of the disease, approximately 56% of the patient population remains unidentified • The unidentified patient population can be better identified through early screening programs and disease awareness campaigns ©Niteo Partners Consulting 2015 10 2013: Total identified patients Hemophilia type Number of patients Hemophilia A 140,313 Hemophilia B 28,430 Hemophilia A (with inhibitors) 4,753 Hemophilia B (with inhibitors) 248 Hemophilia type unknown 2,986 Total identified patients 176,730
  11. 11. Choropleth: Global Registered Patients in 2013 ©Niteo Partners Consulting 2015 11 Source : World Federation of Hemophilia report on the annual global survey 2013
  12. 12. Total Patient Population in Different Countries in 2013 ©Niteo Partners Consulting 2015 12 (Patient Population > 5,000)
  13. 13. TREATMENT OPTIONS ©Niteo Partners Consulting 2015 13
  14. 14. ReplacementTherapy • The most widely used replacement therapy involves the intravenous injection of the missing clot factors to help stop hemorrhaging • Shortcomings of Replacement Therapy: o Transmission of blood-borne disease through infected blood o Development of antibody inhibitors o Complications associated with delayed treatment o Though there is still no permanent fix for hemophilia, most people through timely interventions, and with milder forms of the disease can lead fairly normal lives ©Niteo Partners Consulting 2015 14
  15. 15. Common Medications ©Niteo Partners Consulting 2015 15 Product name Source Hemophilia A Helixate FS (CSL Behring LLC) Kogenate FS (Bayer HealthCare) Advate (Baxalta US Inc) Recombinate (Baxter Healthcare Corporation, & Wyeth BioPharma) ReFacto (Pfizer) Koate-DVI (Kedrion Biopharma) Monoclate-P (CSL Behring LLC) Hemofil M (Baxter) Recombinant Recombinant Recombinant  Recombinant Recombinant Plasma Plasma Plasma Hemophilia B Mononine (CSL Behring LLC) AlphaNine SD (Grifols Biologicals Inc.) BeneFIX (Wyeth Pharmaceuticals Inc.) Profilnine SD (Grifols Biologicals Inc.) Bebulin VH (Baxter) Plasma Plasma Recombinant Plasma Plasma
  16. 16. AlternativeTreatments to ReplacementTherapy ©Niteo Partners Consulting 2015 16
  17. 17. ITITherapy • Treatment of patients who develop antibodies is challenging and done using a method called Immune Tolerance Induction (ITI) therapy which is quite complex, expensive and lengthy • A small percentage of Hemophilia patients develop antibodies as a part of the immune system response to the factor concentrates rendering general treatments ineffective • These antibody inhibitors affect 20-30%[8] of patients diagnosed with severe Hemophilia A and 2-5% of patients with Hemophilia B ©Niteo Partners Consulting 2015 17 Process flow of ITI Therapy
  18. 18. PAYERS IN MAJOR MARKETS ©Niteo Partners Consulting 2015 18
  19. 19. Hemophilia Market in USA • The payers in this market include both Federal Medicaid and Medicare programs as well as state sponsored programs and employer sponsored private insurance • The cost of Hemophilia varies significantly according to the age and life span of the patient ©Niteo Partners Consulting 2015 19
  20. 20. Age and Cost Co-relation ©Niteo Partners Consulting 2015 20 Source : American Society of Hematology
  21. 21. Cost ofTreatment • Factor replacement concentrates, which are now the standard of treatment, account for 45% to 93% of the total medical cost for Hemophilia • Besides age and medication costs, variables in the cost of treatment can be disease severity, familial clustering, phenotypic variability and morbidity influence costs • The expenses of patients who develop inhibitor antibodies is significantly higher and is estimated at USD 697,000annually per patient • Indirect costs include individuals’ and caregivers’ lost productivity, caregivers’ unpaid costs, and reductions in patients quality of life years (QALYs) • Federal Hemophilia Treatment Centers (HTCs) treated 70% of all patients and achieved better outcomes at lower costs as compared to other providers ©Niteo Partners Consulting 2015 21
  22. 22. Average Inpatient Claims – US Market ©Niteo Partners Consulting 2015 22 The cost of inpatient claims associated with Hemophilia is significantly greater than the average claim Source: Milliman actuarial study of Hemophilia 2013
  23. 23. Payer Coverage Criteria – US Market • Being an inherited disorder, family history of the disease is a key criterion in insurance coverage • New Affordable Care Act prohibits lifetime and annual limits on coverage and offers insurance to uninsured people with pre-existing conditions is expected to positively impact Hemophilia patients ©Niteo Partners Consulting 2015 23 Cost Saving Strategies adopted by Payers
  24. 24. Patient Population – Indian Market • Only 16,456patients are registered as against a total estimated patient population of 54,454 • People suffering from hemophilia in India remain largely unidentified • There is heavy under diagnosis with case detection rate of 0.9 per million as compared to 4.3 per million in the US ©Niteo Partners Consulting 2015 24
  25. 25. Burden of Hemophilia • Annual costs incurred based on the severity of the condition and the frequency of occurrence: • Hemophilia remains classified as a low-volume high-cost disease in India and most patients cannot afford private health insurance • The Insurance Act in India does not cover pre-existing hereditary disorders and advanced treatments like factor concentrates remain costly • The Indian market still heavily depends on relatively cheaper plasma derived concentrates which may turn out to be a risky proposition given the spread of blood-borne disease such as HIV, HCV ©Niteo Partners Consulting 2015 25 Category Annual frequency of bleeding episodes Annual Cost (USD)* Severe 12-15 3,000 – 3,800 Moderate 6-8 1,500 – 1,900 Mild 3-4 750 – 1,000 *Conversion Rate: 1 USD = INR 66
  26. 26. LATEST ADVANCEMENTS INTREATMENTS ©Niteo Partners Consulting 2015 26
  27. 27. GeneTherapy • Since Hemophilia is an inherited disorder attributed to Gene mutations, most research for a cure revolves around gene therapy • No gene therapy has been approved, though some successful clinical trials have been carried out in animals as well as humans • Recent studies published advocate the long term safety of such treatments • With research in gene therapy gaining momentum a permanent cure for the condition seems on the horizon • Following are the list of companies or organisations that are advancing gene therapy based assets in the pipeline: ©Niteo Partners Consulting 2015 27 Gene Therapy Process
  28. 28. Recent Developments in GeneTherapy ©Niteo Partners Consulting 2015 28 Company Disease Area Name Status Baxter International Hemophilia B BAX-335 Initial data from Phase I/II clinical trial of Hemophilia B reported in February 2015 Hemophilia A Undisclosed UniQure Hemophilia B AMT-606 Phase I/II trial for Hemophilia B started in 2015 Hemophilia A Undisclosed Dimension Therapeutics Hemophilia A/B Undisclosed Expects to start clinical testing in 2015 Spark Therapeutics Hemophilia B SPK-FIX Phase I/II trials in Hemophilia B in 2015 Hemophilia A Undisclosed Biomarin Pharmaceutical Hemophilia A BMRN-270 Clinical testing in 2015 Sangamo Biosciences Hemophilia A/B Undisclosed Plans to submit Investigational New Drug (IND) application in 2015 Biogen IDEC Hemophilia A/B Undisclosed Potential first trial in 2016
  29. 29. MARKET LANDSCAPE ©Niteo Partners Consulting 2015 29
  30. 30. Market updates •Despite the extremely high costs, investments in gene therapy continue to grow and a genetic cure for hemophilia is no longer a distant possibility •The global market for Hemophilia treatment is poised at USD 5 billion for Hemophilia A and USD 1 billion for Hemophilia B •Hemophilia patients tend to detest frequent short term interventions and new drugs are set to address this need •Long-acting recombinants, which have a considerably longer half life period are about to enter markets this year and could capture considerable market share •The new treatments look increasingly promising in trial phases from the view point of restricting inhibitor development in patients who develop antibodies ©Niteo Partners Consulting 2015 30
  31. 31. Innovative Drugs Pipeline – Hemophilia A ©Niteo Partners Consulting 2015 31 Company Name Status Description Biogen Idec / SOBI rFVIIIFc (BIIB031 or Eloctate) FDA and Health Canada approved in summer 2014 Long-acting recombinant with extended half life Bayer BAY81 8973‐ (Kovaltry in the U.S.) FDA accepted Bayer’s license application in the March 2015 Normal half life recombinant : full length‐ rFVIII manufactured without exposure to human and animal proteins Novo Nordisk Zonovate in Canada and NovoEight in the rest of the world (Turoctocog alfa) Approved by Health Canada in January 2015. NovoEight is approved by the FDA, EMA, and regulatory authorities in Japan and Australia Normal half life recombinant : rFVIII manufactured without exposure to human and animal proteins Octapharma Human cl rhFVIII‐ (simoctocog alfa) Nuwiq Marketing authorization granted in Europe in August 2014 and Canada in November 2014 First rFVIII with human like post‐ translational modifications, which it is hoped will result in a lower rate of inhibitors Novo Nordisk N8 GP (turoctocog‐ alfa pegol) Phase III trial completed in March 2014 Recombinant with half life of 18.4 hours Bayer BAY94 9027‐ Phase III trial completed in Feb 2014 Long acting plasma/albumin free, full length‐ rFVIII Baxter Bax 855 Submitted application to the U.S. FDA in Dec 2014 Pegylated, long acting, plasma/albumin free,‐ full length rFVIII‐ CSL Behring rVIII SingleChain‐ Results of Affinity Phase I/III study released in June 2015 Novel recombinant single chain‐ factor VIII designed to overcome inhibitors Chugai Pharmaceutical Co & Roche Anti factor IXa/X‐ bispecific antibody ACE910 Phase III trial by the end of 2015 Mimics coagulation factor VIII with a half life‐ of three weeks
  32. 32. Innovative Drugs Pipeline – Hemophilia B ©Niteo Partners Consulting 2015 32 Company Name Status Description Biogen Idec/ SOBI rFIXFc (BIIB029 or Alprolix™) Approved in US and Canada in 2015 Fc fusion technology to extend half-life by 2.5 times that of existing therapies Emergent Biosolutions Ixinity in the U.S. (previously IB1001) FDA approved in May 2015 Normal half-life , 3rd gen rFIX manufactured in a Chinese Hamster Ovary cell line without exposure to human and animal proteins Baxter Rixubis(previously Bax 326) FDA approval for pediatric treatment in October 2014. Approved for adults in US and Canada. 3rd generation rFIX CSL Behring rIX FP‐ Applied for approval in 2015 rFIX is fused with recombinant human albumin. Phase III trials showed a longer half life‐ Novo Nordisk NN79 (N9 GP)‐ Marketing authorizations submitted in 2015 Long-acting with reported half life of 93 hours OPKO Health Factor IX CTP‐ Investigational New Drug (IND) application submitted in Jan 2015 FIX fused with a carboxyl terminal peptide to extend half-life
  33. 33. Access related Challenges • High costs associated with safer treatments put them out of the reach of patient populations particularly in developing countries • The access to treatments is also inhibited by supply issues as drug manufacturers are not able to estimate exact patient numbers • Patients are sometimes rendered apprehensive about using treatments due to the possibility of inhibitor development which may increase long-term costs of treatment • The issue of developing inhibitors is something drug manufacturers hope to address in new products • Risks associated with transmission of blood borne diseases through usage of human plasma concentrates still remain a key factor though they are on the decline ©Niteo Partners Consulting 2015 33
  34. 34. FUTURE OUTLOOK ©Niteo Partners Consulting 2015 34
  35. 35. Future Outlook • Haemophilia is a complicated orphan disease with life-long implications on the Quality-of-Life (QOL) of patients, care-givers and communities • Large parts of patient population remains undetected due to lack of proper diagnostic tests and procedures • Currently, there are no ground breaking treatments available in the market and even the ones that are available are expensive for most patients in emerging market countries • However, a lot of progress has happened in the treatment paradigm and there are a lot of new treatments which are advancing through the pipeline, most notably are the genetic therapies used to treat the disease • The biggest challenge for ensuring market access will be to make these newer treatments affordable for vast majority of the patient populations • While discovering and making medicines available is one part of the challenge, a lot needs to be done to address unmet needs across the Haemophilia care continuum to improve outcomes ©Niteo Partners Consulting 2015 35
  36. 36. Future Outlook – Emerging Markets Perspective We have identified 5 such unmet needs – mostly in emerging markets, which if addressed, could significantly improve outlook for patients, prescribers and communities ©Niteo Partners Consulting 2015 36 Poor Diagnosis Rates Lack of Disease Awareness Lack of Training and Medical Expertise Poor Market Access Lack of Data Collection Processes 1 2 3 4 5 ◉ Poor rate of effectiveness of diagnostic tests and procedures is the biggest challenge in Hemophilia. ◉ This is even more important in emerging markets, like India, with large patient populations as poor rate of diagnosis leads to wastage of important healthcare resources and deteriorates health outcomes ◉ Hemophilia is one such disease where very little has been done to identify and then treat patient populations in emerging markets. We believe advocacy from relevant stakeholders in the healthcare system will lead to coordinated action by the government to improve health outcomes ◉ This is one such area which can be addressed immediately as emerging market countries have large prescriber base with strong focus on training. These countries need more disease awareness and disease management programs to better manage the disease ◉ This has always been difficult in emerging markets as most treatments are rendered unaffordable due to economic considerations. Companies and governments have to create incentives for working together either through innovative pricing and access models or through effective risk sharing along patient pathways ◉ It is very important for pharmaceutical companies and patients to share outcomes data as it will ensure that newer treatments are developed more effectively.