As we look to the immediate future, there are two gene therapies currently up for review; the Biologic License Applications (BLAs) for each have been submitted and accepted. These two gene therapies include: (1) etranacogene dezaparvovec, known as AMT-061 (EtranaDez) for the treatment of Hemophilia B, BLA accepted 5/24/2022, PDUFA[1] date 11/24/2022; and (2) valoctocogene roxaparvovec (Roctavian/Valrox) for the treatment of Hemophilia A, BLA accepted 10/12/2022, PDUFA date 3/31/2022. In a recent development regarding the gene therapy valoctocogene roxaparvovec, BioSpace has reported that the FDA requested results from the three-year data analysis of its ongoing Phase III GENEr8-1 study. This could extend the PDUFA date an additional 3-months.[2]
It is estimated that there are between 30,000 and 33,000 males living in the US with hemophilia today.[3] According to the CDC, the prevalence of hemophilia A affects one in every 5,617 male births; about 400 babies are born with hemophilia A each year, of which, one in five will develop an inhibitor. [4],[5],[6] Hemophilia B affects one in every 19,283 male births, of which 3 in 100 will develop an inhibitor. 5,6,7 The severe form of Hemophilia affects 4 in 10 males.5,6,7 The gene therapy for hemophilia A, valoctocogene roxaparvovec, is a single infusion that works by delivering a functional copy of the clotting factor VIII (F8) gene via the adeno-associated virus type 5 (AAV5) into the liver cells.[7],[8] The gene therapy, etranacogene dezaparvovec, for hemophilia B is also a single infusion that works by utilizing the AAV5 as a vector which carries the Padua gene variant of Factor IX (FIX-Padua), which generates FIX proteins that are 5x-8x more active than normal, into the liver cells.[9]
ICER has completed their review of the gene therapies for hemophilia A and B and recommends evidence rating of B+ for etranacogene dezaparvovec and C++ for valoctocogene roxaparvovec when compared to factor prophylaxis.11 ICER has suggested fair pricing $2.9M cap for etranacogene dezaparvovec (price expectation may be up to $4M), and suggested fair pricing of $1.9M cap for valoctocogene roxaparvovec. [10]
Currently there are four FDA approved gene therapies: (1) Luxturna, approved 12/19/2017 for inherited retinal dystrophy (IRD); (2) Zolgensma, approved 5/24/2019 for spinal muscular atrophy (SMA); (3) Zynteglo, approved 8/17/2022 for transfusion-dependent beta thalassemia (TDT); and (4) Skysona, approved 9/16/2022 for cerebral adrenoleukodystrophy (CALD).
Article written by Kathy Clark, RN, BSN, CMCN, RIT, Vice President, Managed Care for Summit Reinsurance Services, Inc. For more information about how this may affect your plan, please contact your Summit ReSources care specialist.
Notes:
[1] Prescription Drug User Fee Act (PDUFA) –Once the BLA is accepted a PDFUA date is set by the FDA, this is the date by which the FDA must respond to a BLA (approve, not approve, ask for more information).
[2] https://www.biospace.com/article/biomarin-faces-a-potential-3-month-review-delay-for-hemophilia-a-gene-therapy/
[3] https://www.cdc.gov/ncbddd/hemophilia/features/keyfinding-hemophilia-occurrence-US.html
[4] Inhibitors and Hemophilia. https://www.cdc.gov/ncbddd/hemophilia/inhibitors.html
[5]https://www.cdc.gov/ncbddd/hemophilia/data.html#:~:text=Hemophilia%20A%20affects%201%20in,with%20hemophilia%20A%20each%20year.
[6] https://www.cdc.gov/ncbddd/hemophilia/features/keyfinding-hemophilia-occurrence-US.html
[7] Ozelo MC, Mahlangu J, Pasi KJ, Giermasz A, Leavitt AD, Laffan M, Symington E, Quon DV, Wang JD, Peerlinck K, Pipe SW, Madan B, Key NS, Pierce GF, O'Mahony B, Kaczmarek R, Henshaw J, Lawal A, Jayaram K, Huang M, Yang X, Wong WY, Kim B; GENEr8-1 Trial Group. Valoctocogene Roxaparvovec Gene Therapy for Hemophilia A. N Engl J Med. 2022 Mar 17;386(11):1013-1025. doi: 10.1056/NEJMoa2113708. PMID: 35294811.
[8] https://hemophilianewstoday.com/bmn-270/
[9] https://hemophilianewstoday.com/amt-061/
[10] Tice JA, Walton S, Herce-Hagiwara B, Fahim SM, Moradi A, Sarker J, Chu J, Agboola F, Pearson SD, Rind DM. Gene Therapy for Hemophilia B and An Update on Gene Therapy for Hemophilia A: Effectiveness and Value; Evidence Report. Institute for Clinical and Economic Review, November 2, 2022. https://icer.org/assessment/hemophilia-a-and-b-2022/