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A compilation of news and research about nonmalignant hematologic disorders , including :

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IN THE LITERATURE

Questions and Controversies in Iron-Deficiency Anemia

The New Rules of TTP Management

Anticoagulants Safe and Efficacious in Children With CVC-VTE

Highlights From Recent Hematology Meetings

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OCTOBER 2020

yet know what fully accounts for that variability .”

Ongoing trials are all enrolling patients without anti-FVIII or FIX antibodies or inhibitors to the factor products used to treat or prevent their bleeding episodes , making the approximately 30 % of people with hemophilia A and 3 % of people with hemophilia B ineligible for most gene therapy platforms . Spark is developing a gene therapy , SPK-8016 , specifically for individuals with hemophilia A with inhibitors that is currently in phase I / II trials . The difference between this therapy and SPK-8011 is proprietary information , Dr . Monahan told ASH Clinical News .

The trials are forging ahead – with caution . “ Systemic AAV vectors were first used in hemophilia clinical trials almost 20 years ago now , but we had little confirmation that the participants had sustained expression of the factor genes encoded by the vectors ,” explained Dr . George . “ Over the past decade , the study of systemic AAV vectors for hemophilia and also other disorders has expanded .”

The longest follow-up demonstrating sustained vector expression with an AAV gene therapy was in the initial successful hemophilia B trial , which reported safety and efficacy data from up to 8 years . ¹⁰ However , she said , “ in my mind , the long-term safety of systemic AAV is an unanswered question .”

Dr . Croteau agreed . “ From decades ’ worth of

data across hemophilia and other diseases using AAV-based gene therapy , we have not seen any significant negative long-term impacts of the therapy – particularly in the adult population ,” she said . “ Still , caution and attention to longitudinal safety and efficacy monitoring are needed .”

“ Gene therapy is potentially a paradigmchanging strategy for hemophilia A care ,” added Dr . George . “ The optimism around this area is high , and there are many clinical trial programs underway so that we will soon be able to answer some of these outstanding questions .” — By Anna Azvolinsky

References

1 . BioMarin press release . BioMarin Submits Biologics License Application to U . S . Food and Drug Administration for Valoctocogene Roxaparvovec to Treat Hemophilia A . Accessed October 6 , 2020 , from https :// investors . biomarin . com / 2019-12-23-BioMarin-Submits-Biologics-License-Application-to-U-S- Food-and-Drug-Administration-for-Valoctocogene-Roxaparvovec-to-Treat- Hemophilia-A .

2 . BioMarin press release . BioMarin receives Complete Response Letter ( CRL ) from FDA for valoctocogene roxaparvovec gene therapy for severe hemophilia A . August 19 , 2020 . Accessed October 6 , 2020 , from https :// investors . biomarin . com / 2020-08-19-BioMarin-Receives-Complete-Response-Letter- CRL-from-FDA-for-Valoctocogene-Roxaparvovec-Gene-Therapy-for-Severe- Hemophilia-A .

3 . Centers for Disease Control and Prevention . Data & statistics on hemophilia . Accessed October 6 , 2020 , from https :// www . cdc . gov / ncbddd / hemophilia / data . html .

4 . uniQure press release . uniQure announces achievement of target patient dosing in HOPE-B pivotal trial of AMT-061 ( etranacogene dezaparvovec ) in hemophilia B . Accessed October 6 , 2020 , from https :// www . globenewswire . com / news-release / 2020 / 03 / 26 / 2006871 / 0 / en / uniQure-Announces- Achievement-of-Target-Patient-Dosing-in-HOPE-B-Pivotal-Trial-of-AMT-061- Etranacogene-Dezaparvovec-in-Hemophilia-B . html .

5 . Pfizer press release . Pfizer Investor Day features significant number of pipeline advances for COVID-19 programs and across numerous therapeutic areas . Accessed October 6 , 2020 , from https :// investors . pfizer . com / investor-news / press-release-details / 2020 / Pfizer-Investor-Day-Features-Significant- Number-of-Pipeline-Advances-for-COVID-19-Programs-and-Across- Numerous-Therapeutic-Areas / default . aspx .

6 . BioMarin press release . BioMarin announces that phase 3 cohort of valoctocogene roxaparvovec , gene therapy study in severe hemophilia A met pre-specified criteria for regulatory submissions in the U . S . and Europe . Accessed October 6 , 2020 , from https :// investors . biomarin . com / 2019- 05-28-BioMarin-Announces-that-Phase-3-Cohort-of-Valoctocogene- Roxaparvovec-Gene-Therapy-Study-in-Severe-Hemophilia-A-Met-Pre- Specified-Criteria-for-Regulatory-Submissions-in-the-U-S-and-Europe .

7 . Pasi KJ , Rangarajan S , Mitchell N , et al . Multiyear follow-up of AAV5-hFVIII-SQ gene therapy for hemophilia A . N Engl J Med . 2020 ; 382:29-40 .

8 . George L , Eyster E , Ragni M , et al . Phase I / II trial of SPK-8011 : Stable and durable FVIII expression for > 2 years with significant ABR improvements in initial dose cohorts following AAV-mediated FVIII gene transfer for hemophilia A . Abstract OC 03.5 . Presented at ISTH 2020 Virtual Congress ; July 12-14 , 2020 .

9 . Pfizer press release . Pfizer and Sangamo announce updated phase 1 / 2 results showing sustained factor VIII activity levels and no bleeding events or factor usage in 3e13 vg / kg cohort following giroctocogene fitelparvovec ( SB-525 ) gene therapy . Accessed October 6 , 2020 , from https :// investors . pfizer . com / investor-news / press-release-details / 2020 / Pfizer-and-Sangamo-Announce- Updated-Phase-12-Results-Showing-Sustained-Factor-VIII-Activity-Levelsand-No-Bleeding-Events-or-Factor-Usage-in-3e13-vgkg-Cohort-Followinggiroctocogene-fitelparvovec-SB-525-Gene-Therapy / default . aspx .

10 . Nathwani AC , Reiss U , Tuddenham E , et al . Adeno-associated mediated gene transfer for hemophilia B : 8-year follow-up and impact of removing “ empty viral particles ” on safety and efficacy of gene transfer . Blood . 2018 ; 132 ( Supplement 1 ): 491 .

Your source for worldwide news and perspectives on hematology / oncology vol 06 | no 11 September 2020 www . ASHClinicalNews . org

INSIDE

EDITOR ’ S CORNER

Ari Giagounidis Asks What ’ s Your Major Motivation ?

WRITTEN IN BLOOD

How Do HIV Therapies Affect Blood Donation Safety ?

LITERATURE SCAN

Evaluating Selinexor in Relapsed / Refractory DLBCL

HOW I TREAT IN BRIEF

Acute Myeloid Leukemia in the Era of New Drugs

ON LOCATION

Coverage From Recent Hematology Meetings

The Rise of

PLUS

How preprint servers are helping physicians and scientists keep pace with discovery

FEATURE

Calculating the Costs of COVID-19

vol 06 | no 12 October 2020

INSIDE

EDITOR ’ S CORNER

Alexandra Wolanskyj- Spinner on Teaching Outside the Boundaries

A DAY IN THE LIFE

Blood , Sweat , and Smears : What Does a Hematopathologist Do ?

HOW I TEACH

Navigating the COVID-19 Classroom

WRITTEN IN BLOOD

Low Risk of Post- Discharge VTE in Patients With COVID-19

LITERATURE SCAN

Does Inhaled Cannabis Help With SCD Pain ?

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Diversity , Equity , and Inclusion

How a renewed awareness about racial injustice embedded in society is changing the American health care system

Candidates must have a strong clinical background , an eye for medical trends in hematology , a working knowledge of ASH programs and initiatives , and an interest in developing content that would appeal to other medical disciplines , as well as demonstrated writing , reviewing , and editing skills . The three-year term will begin January 1 , 2021 .

To apply , send the following to khubing @ hematology . org no later than November 11 , 2020 :

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