Biomarin Pharmaceutical Inc. · NASDAQ:BMRN

Biomarin Pharmaceutical — Thrombosis & Hemostasis Summit of North America 2024

17 slides from Biomarin Pharmaceutical's conference presentation, 2024

  1. Slide 1: Safety and efficacy of valoctocogene roxaparvovec gene transfer for severe hemophilia A: 4-year update

    Safety and efficacy of valoctocogene roxaparvovec gene transfer for severe hemophilia A: an update from 4 years after treatment 1Adult Hemophilia Treatment Center, University of California San Francisco, San Francisco, CA, USA; 2Hemophilia Comprehensive Care Center, Charlotte Maxeke Johannesburg Aca

  2. Slide 2: Disclosures

    • I have served on advisory boards and speakers bureaus or as a consultant for Bayer, BioMarin Pharmaceutical Inc., CSL Behring, Genentech, Novo Nordisk, Octapharma, Sanofi, and Takeda 2

  3. Slide 3: Valoctocogene roxaparvovec for severe hemophilia A

    Valoctocogene roxaparvovec for severe hemophilia A Valoctocogene roxaparvovec (AAV5-hFVIII-SQ) is a liver-directed gene therapy that transfers a FVIII coding sequence to enable FVIII production in people with severe hemophilia A (FVIII ≤1 IU/dL)1,2 In the open-label, phase 3 GENEr8-1 trial, particip

  4. Slide 4: Study design

    Study design Eligibility Endpoints • Adult men with severe hemophilia A (FVIII ≤1 IU/dL) • FVIII activity • Previously receiving FVIII prophylaxis • Change from baseline during post-prophylaxis • No history of FVIII inhibitors or anti-AAV5 antibodies – Annualized bleeding rate • No significant liver

  5. Slide 5: Participant disposition

    Participant disposition ITT population All participants infused N = 134 Rollover from BMN 270-902 Directly enrolled Directly enrolled HIV-negative, N = 112 HIV-negative, n = 20 HIV-positive, n = 2 mITT ≥5-year mITT population subgroup HIV-negative n = 17 N = 132 Completed study (5 years), n = 15 Dis

  6. Slide 6: Baseline characteristics

    Baseline characteristics Rollover population mITT ITT Baseline characteristics N = 112 N = 132 N = 134 Age, years, mean ± SD 31.8 ± 10.6 31.4 ± 10.1 31.7 ± 10.3 Race, n (%) White 78 (69.6) 94 (71.2) 96 (71.6) Asian 17 (15.2) 19 (14.4) 19 (14.2) Black or African American 14 (12.5) 15 (11.4) 15 (11.2)

  7. Slide 7: No new safety signals in year 4

    No new safety signals in year 4 ITT population With AEs in year 4 In year 4: Participants, n (%) (N = 131) AEs 106 (80.9) No new safety signals SAEs 13 (9.9) • ALT elevations remained the most common AE Treatment-related AEsa 10 (7.6) in year 4 Glucocorticoid-related AEs 1 (0.8) No treatment-related

  8. Slide 8: ALT elevation and corticosteroid use

    ALT elevation and corticosteroid use ITT population With AEs in year 4 In year 4: During year 4 (N = 131) 56 (42.7%) participants had an ALT ALT elevation >ULN, n (%) 21 (16.0) elevation ALT elevation >1.5x baseline, n (%) 55 (42.0) No participants used glucocorticoids to manage ALT elevations Used

  9. Slide 9: FVIII activity between years 3 and 4 (chromogenic assay)

    FVIII activity between years 3 and 4 mITT population (chromogenic substrate assay) Week 156 Mean ± SE: 18.4 ± 2.7 IU/dL Median (Q1, Q3): 8.3 (3.0, 17.2) IU/dL Week 208 100 Mean ± SE: 16.1 ± 2.5 IU/dL Median (Q1, Q3): 6.7 (2.8, 17.8) IU/dL Mean ± SE FVIII activity (CSA; IU/dL) 75 50 25 0 -25 n = 132

  10. Slide 10: FVIII activity ranges at the end of each year (chromogenic assay)

    FVIII activity ranges at the end of year 4 mITT population (chromogenic substrate assay) Most participants remain in the mild hemophilia range 100 Median FVIII activity per CSA 10.6% 7.7% 15.9% ≥40 IU/dL ≥5 to <40 IU/dL 80 37.1% ≥3 to <5 IU/dL <3 IU/dL (LLOQ) Part icipants, % 52.3% 60 55.3% 58.3% 40

  11. Slide 11: FVIII activity between years 3 and 4 (one-stage assay)

    FVIII activity between years 3 and 4 mITT population (one-stage assay) Week 156 Mean ± SE: 28.1 ± 3.6 IU/dL Median (Q1, Q3): 16.0 (5.3, 30.4) IU/dL Week 208 100 Mean ± SE: 27.1 ± 4.0 IU/dL Median (Q1, Q3): 13.5 (5.3, 29.1) IU/dL Mean ± SE FVIII activity (OSA; IU/dL) 75 50 25 0 -25 n = 132 132 132 13

  12. Slide 12: FVIII activity ranges at the end of each year (one-stage assay)

    FVIII activity ranges at the end of year 4 mITT population (one-stage assay) Most participants remain in the mild hemophilia range 100 Median FVIII activity per OSA 18.9% 16.9% ≥40 IU/dL 27.3% ≥5 to <40 IU/dL 80 ≥1 to <5 IU/dL 50.8% <1 IU/dL (LLOQ) Participants, % 60 61.5% 60.6% 56.8% 40 41.7% 20 11

  13. Slide 13: Reduction in treated bleeds maintained over 4 years

    Reduction in treated bleeds maintained over 4 years Rollover population ABR for treated bleeds decreased In year 4, >70% of participants >80% from baseline to year 4 had no treated bleeds 15 81.3% reduction 100 82.1% 83.9% 4.8 80 74.5% 73.6% ABR (bleeds/year) Mean + SD Proportion (%) 10 Median (Q3)

  14. Slide 14: Reduction of FVIII infusion rate maintained through year 4

    Reduction of FVIII infusion rate maintained through year 4 Rollover population Annualized FVIII infusion rate decreased Over 4 years, 22 participants resumed >90% from baseline to year 4 prophylaxis ITT population (N = 134) 250 92.2% reduction 1.0 0.9 Prophylactic treatment-free 200 135.9 0.8 AFR (i

  15. Slide 15: Haemo-QOL-A improvement maintained after 4 years

    Haemo-QOL-A improvement maintained after 4 years mITT population Haemo-QOL-A Total Score increased 6.5 points from baseline, exceeding the CID of 5.51 20 18 from baseline in Haemo-QOL-A Total and domain scores 16 Mean ± 95% CI change ** ** 10.7 10.5 ** ** 14 ** 9.2 9.2 9.7 ** * 7.7 7.9 12 ** ** ** 7

  16. Slide 16: Single infusion provided durable bleeding protection and improved HRQOL

    After 4 years, a single infusion of valoctocogene roxaparvovec provided durable bleeding protection and improved HRQOL with an acceptable safety profile No new safety signals Durable hemostatic efficacy • ALT elevation remained the most • Rate of treated bleeds during common AE in year 4 year 4 rema

  17. Slide 17: Thank you to all trial participants, their families, and investigators

    • Thank you to all trial participants, their families, study site personnel, and investigators • Funding for this study was provided by BioMarin Pharmaceutical Inc. • Medical writing support was provided by Amin Ghane, PhD, of AlphaBioCom, a Red Nucleus company, and funded by BioMarin Pharmaceutical

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