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Disease Analysis: Hemophilia

  • ID: 3797432
  • Report
  • June 2021
  • Region: Global
  • 102 Pages
  • Datamonitor Healthcare
Definition

Hemophilia is a rare, inherited X chromosome-linked bleeding disorder in which deficiencies in clotting factors prevent blood from clotting normally. Injuries therefore result in prolonged periods of bleeding. There are two types of hemophilia, A and B, with similar signs and symptoms but different genetic defects.

Latest Key Takeaways
  • The publisher estimates that in 2018, there were approximately 180,750 diagnosed prevalent cases of hemophilia A and 35,950 diagnosed prevalent cases of hemophilia B worldwide. These figures are forecast to increase to 193,730 cases and 38,570 cases, respectively, by 2027. There were approximately 82,550 diagnosed prevalent cases of von Willebrand disease (VWD) worldwide in 2018, which is forecast to increase to 86,150 cases by 2027.
  • Current treatments are largely focused on replacing factor VIII (fVIII) or factor IX (fIX), the deficiency of which causes hemophilia A or B, respectively. Recombinant fVIII and fIX are at the top of algorithms in the US and EU treatment guidelines. Until recently, full-length recombinant fVIII agents Advate and Kogenate, and the fIX agent BeneFIX, have dominated the hemophilia space and have held the largest portion of market share. However, these drugs have been steadily losing market share to extended half-life recombinant factor products (EHLs) and Hemlibra, as physicians switch patients to newer-generation products with improved dosing frequencies. During 2018-20, sales of Advate more than halved (from $2,806m in 2018 to $1,213m in 2020) due to fierce competition primarily from Roche’s Hemlibra, which was awarded a label expansion in the US and EU in the first quarter of 2019.
  • The therapeutic strategies for hemophilia were revolutionized after the introduction of replacement factors during the late 1990s and early 2000s, which were followed by EHLs over the past decade. Currently, the hemophilia market is undergoing a third revolution, with an anticipated shift towards alternative coagulation promoters and gene therapy.
  • While the 2017 launch of Roche’s Hemlibra for the treatment of hemophilia A patients with fVIII inhibitors did not make a large impact on the hemophilia market, the extension of its US and EU labels in 2018 to include hemophilia A patients without inhibitors triggered a large increase in sales. Hemlibra has captured market share from a host of replacement factors and EHLs and is set to achieve market leader status over the forecast period. Hemlibra is clinically more attractive than rival products because of its novel inhibitor-independent mechanism of action, its dosing schedule of once every two weeks, and its ability to be self-administered subcutaneously in a market dominated by intravenous agents.
  • There are a number of pipeline candidates in the hemophilia space which may make a significant impact in the market over the forecast period. Based on discussions with key opinion leaders (KOLs), the publisher expects that Roche’s Hemlibra will further extend its lead in the hemophilia space, having captured market leader status from Takeda’s Advate in 2019. Gene therapies are expected to have initially muted uptake because of a high upfront cost for payers ($2m-$3m) and an initial reluctance from prescribers owing to uncertainty over their long-term efficacy and safety.
  • BIVV001, a next-generation replacement fVIII, is expected to launch in the hemophilia A market in 2022. Although BIVV001 has an extended dosing frequency of once weekly and has achieved higher fVIII expression levels compared to established replacement fVIII therapies, the publisher expects the drug to struggle against market leader Hemlibra. Hemlibra benefits from a superior dosing frequency of once every two weeks, is not inhibited by the development of neutralizing antibodies (nABs), and is administered subcutaneously. As older therapies in the hemophilia A market are gradually cannibalized by Hemlibra, the market share that BIVV001 can potentially capture from replacement fVIII therapies is diminishing.
  • In the hemophilia B space, pipeline alternative coagulation promoters such as the siRNA agent fitusiran and the tissue factor pathway inhibitors (TFPIs) concizumab and marstacimab may struggle to gain uptake due to safety concerns. These drugs meet the need for an effective therapy for hemophilia B patients with inhibitors, provide a more convenient subcutaneous route of administration, and, in the case of fitusiran, provide an impressive once-monthly dosing regimen. However, whether these drugs will come to market is still unclear given substantial safety concerns. These concerns include two thrombotic events in Phase II trials for fitusiran, one of which was fatal, and three thrombotic adverse events in Phase III trials for concizumab, as well as the suspension of four previous TFPI inhibitor candidates. Concerning safety events have not yet been observed in a single Phase I/II study of marstacimab, but the safety of the class as a whole is now in doubt. Given these safety concerns and a lack of physician familiarity, it seems unlikely these drugs will rival recombinant fIX market leaders BeneFIX and Alprolix for the treatment of hemophilia B patients without inhibitors.
  • Despite receiving a complete response letter in 2020, Roctavian (valoctocogene roxaparvovec) remains the most advanced gene therapy in the hemophilia A space, and assuming EU and US approvals in 2022 and 2023, respectively, BioMarin is expected to launch the product at a price of $2m-$3m per patient. This delay in approval is a significant blow for BioMarin, which had hoped to establish itself in the space 2-3 years ahead of major competitors Pfizer and Roche, which have greater commercial resources. With the projected launches of Roctavian and SB-525 now within months of one another, BioMarin will face competition from Pfizer earlier than previously expected.
  • Additionally, the extremely high upfront cost of Roctavian will be a significant deterrent to uptake, and the publisher expects its initial use to be limited to severe hemophilia patients on chronic prophylaxis therapy. While the gene therapy meets the high unmet need for a long-term therapy, with a projected eight-year interval between doses, Roctavian may face initial payer resistance due to the lack of long-term safety and efficacy data, as the follow-up period in current studies has been limited to five years.
  • There is also considerable competition to be the first-in-class hemophilia B gene therapy, with uniQure and Pfizer the current frontrunners. UniQure’s AMT-061 is expected to launch slightly ahead of Pfizer’s PF-06838435, assuming there are no obstacles to approval. Both therapies have shown strong efficacy (ABRs < 1), in line with the current standard of care, and favorable safety profiles, with PF-06838435 having the added benefit of four years of follow-up data from its Phase II trial. The establishment of a licensing agreement between uniQure and CSL Behring will provide the commercial resources needed to maximize sales of AMT-061. Freeline Therapeutics’ FLT180a, a late entrant into the hemophilia B gene therapy race, remains several years behind its competitors. Notably, the drug has demonstrated higher fIX levels in a Phase I/II trial and has the potential to be a best-in-class therapy.
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OVERVIEW
  • Latest key takeaways
DISEASE BACKGROUND
  • Definition
  • Patient segmentation
  • Etiology
  • Von Willebrand disease
  • Hemophilia symptoms
  • VWD symptoms
  • Hemophilia and VWD complications
  • Diagnosis
  • Treatment options
TREATMENT

EPIDEMIOLOGY
  • Prevalence methodology
MARKETED DRUGS

PIPELINE DRUGS

KEY REGULATORY EVENTS
  • Relief For UniQure Hemophilia Program Sends Ball To FTC’s Court
  • BioMarin Ready To Talk To FDA About Gene Therapy CRL
  • BioMarin Pulls EU Hemophilia Gene Therapy Filing, But Is Not Giving Up
  • New Designations Set To Speed Hemlibra, CAR-T In China
  • Not Such A Sure Thing: FDA Knocks Back BioMarin’s Roctavian
PROBABILITY OF SUCCESS

LICENSING AND ASSET ACQUISITION DEALS
  • Finance Watch: BioAtla, Virios And Scopus Launch Latest US IPOs
  • Atomwise, GC Pharma Team Up On Novel Hemophilia Therapies
  • uniQure Hemophilia B Deal With CSL Leaves M&A Fans Miffed
DRUG ASSESSMENT MODEL
  • Gene therapy for hemophilia A
  • Gene therapy for hemophilia B
CLINICAL TRIAL LANDSCAPE
  • Sponsors by status
  • Sponsors by phase
  • Recent events
MARKET DYNAMICS

FUTURE TRENDS
  • The hemophilia market will continue to expand over the forecast period
  • Hemlibra will continue to capture market share from replacement factors in the hemophilia A space
  • Pipeline alternative coagulation promoters will capture a limited amount of market share in the hemophilia B space
  • Uptake of gene therapy will be limited by high upfront costs and uncertainty over long-term effectiveness
CONSENSUS FORECASTS

RECENT EVENTS AND ANALYST OPINION
  • Roctavian for Hemophilia A (May 19, 2021)
  • Etranacogene Dezaparvovec for Hemophilia B (March 29, 2021)
  • Roctavian for Hemophilia A (January 10, 2021)
  • Etranacogene Dezaparvovec for Hemophilia B (December 21, 2020)
  • FLT180a for Hemophilia B (December 14, 2020)
  • Etranacogene Dezaparvovec for Hemophilia B (December 8, 2020)
  • Fitusiran for Hemophilia A and B (October 30, 2020)
  • Roctavian for Hemophilia A (August 18, 2020)
  • Concizumab for Hemophilia A and B (August 13, 2020)
  • Roctavian for Hemophilia A (June 17, 2020)
  • Concizumab for Hemophilia A and B (March 16, 2020)
KEY UPCOMING EVENTS

KEY OPINION LEADER INSIGHTS

UNMET NEEDS

BIBLIOGRAPHY

APPENDIX

LIST OF FIGURES
Figure 1: Hemophilia etiology
Figure 2: Trends in diagnosed prevalent cases of hemophilia A, 2018–27
Figure 3: Trends in diagnosed prevalent cases of hemophilia B, 2018–27
Figure 4: Trends in diagnosed cases of Von Willebrand disease, 2018–27
Figure 5: Overview of pipeline drugs for hemophilia in the US
Figure 6: Pipeline drugs for hemophilia, by company
Figure 7: Pipeline drugs for hemophilia, by drug type
Figure 8: Pipeline drugs for hemophilia, by classification
Figure 9: Probability of success in the hemophilia pipeline
Figure 10: The publisher’s drug assessment summary for hemophilia
Figure 11: Clinical trials in hemophilia
Figure 12: Top 10 drugs for clinical trials in hemophilia
Figure 13: Top 10 companies for clinical trials in hemophilia
Figure 14: Trial locations in hemophilia
Figure 15: Hemophilia trials status
Figure 16: Hemophilia trials sponsors, by phase
Figure 17: Market dynamics in hemophilia
Figure 18: Future trends in hemophilia
Figure 19: Roctavian for Hemophilia A (May 19, 2021): Phase I/II - PoC
Figure 20: Roctavian for Hemophilia A (January 10, 2021): Phase I/II - PoC, Phase III - GENEr8-1 (6E13 vg/kg)
Figure 21: Etranacogene Dezaparvovec for Hemophilia B (December 8, 2020): Phase III - HOPE-B
Figure 22: Roctavian for Hemophilia A (June 17, 2020): Phase I/II - PoC
Figure 23: Key upcoming events in hemophilia
Figure 24: Unmet needs in hemophilia, physician survey results

LIST OF TABLES
Table 1: Drug classes for hemophilia A, B, and VWD
Table 2: MASAC recommendations for hemophilia A, B, and VWD
Table 3: Gender distributions of diagnosed prevalent cases of hemophilia A, hemophilia B, and Von Willebrand disease
Table 4: Diagnosed prevalent cases of hemophilia A, 2018–27
Table 5: Diagnosed prevalent cases of hemophilia B, 2018–27
Table 6: Diagnosed prevalent cases of Von Willebrand disease, 2018–27
Table 7: Marketed drugs for hemophilia A
Table 8: Marketed drugs for hemophilia B
Table 9: Marketed drugs for hemophilia A and B
Table 10: Marketed drugs for Von Willebrand disease
Table 11: Pipeline drugs for hemophilia A in the US
Table 12: Pipeline drugs for hemophilia B in the US
Table 13: Pipeline drugs for both hemophilia A and B in the US
Table 14: Pipeline drugs for Von Willebrand disease in the US
Table 15: Historical global sales, by drug ($m), 2016–20
Table 16: Forecasted global sales, by drug ($m), 2021–25
Table 17: Roctavian for Hemophilia A (May 19, 2021)
Table 18: Etranacogene Dezaparvovec for Hemophilia B (March 29, 2021)
Table 19: Roctavian for Hemophilia A (January 10, 2021)
Table 20: Etranacogene Dezaparvovec for Hemophilia B (December 21, 2020)
Table 21: FLT180a for Hemophilia B (December 14, 2020)
Table 22: Etranacogene Dezaparvovec for Hemophilia B (December 8, 2020)
Table 23: Fitusiran for Hemophilia A and B (October 30, 2020)
Table 24: Roctavian for Hemophilia A (August 18, 2020)
Table 25: Concizumab for Hemophilia A and B (August 13, 2020)
Table 26: Roctavian for Hemophilia A (June 17, 2020)
Table 27: Concizumab for Hemophilia A and B (March 16, 2020)
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