BOSTON - Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) and CRISPR Therapeutics (Nasdaq: CRSP) announced today that the U.S. Food and Drug Administration (FDA) has approved CASGEVY (exagamglogene autotemcel [exa-cel]), a CRISPR/Cas9 genome-edited cell therapy, for the treatment of sickle cell disease (SCD) in patients 12 years and older with recurrent vaso-occlusive crises (VOCs).
This approval means that for the first time, approximately 16,000 patients with SCD may be eligible for a durable one-time therapy that offers the potential of a functional cure for their disease by eliminating severe VOCs and hospitalizations caused by severe VOCs.
'CASGEVY's approval by the FDA is momentous: it is the first CRISPR-based gene-editing therapy to be approved in the U.S. As importantly, CASGEVY is a first-in-class treatment that offers the potential of a one-time transformative therapy for eligible patients with sickle cell disease,' said Reshma Kewalramani, M.D., Chief Executive Officer and President of Vertex. 'I want to convey my deepest gratitude to the patients and investigators whose trust in this program paved the way for this landmark approval.'
'When our company was founded, we had a vision to translate CRISPR technology into multiple breakthrough therapies. So, this U.S. approval of the first-ever medicine using CRISPR gene editing is breathtaking, and a truly humbling moment for me personally and for the whole organization,' said Samarth Kulkarni, Ph.D., Chairman and Chief Executive Officer of CRISPR Therapeutics.
'It has been remarkable to be part of this groundbreaking program,' said Stephan Grupp, M.D., Ph.D., Section Chief of the Cellular Therapy and Transplant Section and Director of the Kelly Center for Cancer Immunotherapy at the Children's Hospital of Philadelphia, and Steering Committee Chair for the CLIMB-121 clinical program. 'CASGEVY has the potential to be a transformative treatment for patients, and I look forward to continuing the work to ensure eligible patients can access this therapy across the country.'
The administration of CASGEVY requires specialized experience in stem cell transplantation; therefore, Vertex is engaging with experienced hospitals to establish a network of independently operated, authorized treatment centers (ATCs) throughout the U.S. to offer CASGEVY to patients. The following ATCs are already activated
Boston Medical Center in Boston, Mass.
Children's National Hospital in Washington, D.C.
City of Hope Children's Cancer Center in Los Angeles, Calif.
Medical City Children's Hospital in Dallas, Texas
Methodist Children's Hospital in San Antonio, Texas
Nationwide Children's Hospital in Columbus, Ohio
The Children's Hospital at TriStar Centennial in Nashville, Tenn.
The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute in Columbus, Ohio
University of Chicago/Comer Children's Hospital in Chicago, Ill.
Additional ATCs will be activated in the coming weeks and a complete list of ATCs, including updates following approval, can be accessed at CASGEVY.com.
About CASGEVY (exagamglogene autotemcel [exa-cel])
CASGEVY is a genome-edited cellular therapy consisting of autologous CD34+ hematopoietic stem cells (HSCs) edited by CRISPR/Cas9 technology at the erythroid-specific enhancer region of the BCL11A gene. CASGEVY is intended for one time administration via a hematopoietic stem cell transplant procedure where the patient's own CD34+ cells are modified to reduce BCL11A expression in erythroid lineage cells, leading to increased fetal hemoglobin (HbF) production. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. CASGEVY has been shown to reduce or eliminate vaso-occlusive crises for patients with SCD.
CASGEVY was granted a conditional marketing authorization in Great Britain by the U.K. Medicines and Healthcare products Regulatory Agency and by the National Health Regulatory Authority in Bahrain for patients 12 years of age and older with SCD characterized by recurrent vaso-occlusive crises or transfusion-dependent beta thalassemia (TDT), for whom hematopoietic stem cell transplantation is appropriate and a human leukocyte antigen matched related hematopoietic stem cell donor is not available. CASGEVY is currently under review by the European Medicines Agency and the Saudi Food and Drug Agency for both SCD and TDT.
The use of CASGEVY for the treatment of TDT in the U.S. remains investigational. Vertex has submitted a BLA to the U.S. FDA for the potential use of CASGEVY for patients 12 years and older with TDT and has been assigned a Prescription Drug User Fee Act (PDUFA) target action date of March 30, 2024.
About the Vertex/CRISPR Collaboration Financial Reporting
Vertex leads global development, manufacturing and commercialization of CASGEVY with support from CRISPR Therapeutics. In conjunction with the FDA approval of CASGEVY, Vertex will make a $200 million milestone payment to CRISPR, which will be capitalized and amortized to cost of sales. Additionally, Vertex will record 100 percent of CASGEVY revenues; costs of sales and selling, general and administrative expenses and will record CRISPR's 40 percent share in the net profits or losses from CASGEVY within its cost of sales. Lastly, Vertex will record 60 percent of research and development expenses, net of CRISPR's 40 percent share.
About Sickle Cell Disease
Sickle cell disease (SCD) is a debilitating, progressive and life-shortening disease. SCD patients report health-related quality of life scores well below the general population, and the lifetime health care costs in the U.S. of managing SCD for patients with recurrent VOCs is estimated between $4 and $6 million. SCD is an inherited blood disorder that affects the red blood cells, which are essential for carrying oxygen to all organs and tissues of the body. SCD causes severe pain, organ damage and shortened life span due to misshapen or 'sickled' red blood cells. The clinical hallmark of SCD is VOCs, which are caused by blockages of blood vessels by sickled red blood cells and result in severe and debilitating pain that can happen anywhere in the body at any time. SCD requires a lifetime of treatment and results in a reduced life expectancy. In the U.S., the median age of death for patients living with SCD is approximately 45 years. A cure for SCD today is a stem cell transplant from a matched donor, but this option is only available to a small fraction of patients living with SCD because of the lack of available donors.
Helping Patients on the CASGEVY Journey
Vertex Connects is a program for eligible patients in the U.S. who have been prescribed CASGEVY. Through Vertex Connects, Care Managers are available to provide educational resources, communications and support to navigate the treatment journey, and additional assistance is available for eligible patients.
U.S. INDICATIONS AND IMPORTANT SAFETY INFORMATION FOR CASGEVY
CASGEVY is a one-time therapy used to treat people aged 12 years and older with sickle cell disease (SCD) who have frequent vaso-occlusive crises or VOCs.
CASGEVY is made specifically for each patient, using the patient's own edited blood stem cells, and increases the production of a special type of hemoglobin called hemoglobin F (fetal hemoglobin or HbF). Having more HbF increases overall hemoglobin levels and has been shown to improve the production and function of red blood cells. This can eliminate VOCs in people with SCD.
About Vertex
Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has approved medicines that treat the underlying causes of multiple chronic, life-shortening genetic diseases - cystic fibrosis, sickle cell disease and transfusion-dependent beta thalassemia - and continues to advance clinical and research programs in these diseases. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including APOL1-mediated kidney disease, acute and neuropathic pain, type 1 diabetes and alpha-1 antitrypsin deficiency.
Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia and Latin America. Vertex is consistently recognized as one of the industry's top places to work, including 14 consecutive years on Science magazine's Top Employers list and one of Fortune's 100 Best Companies to Work For.
About CRISPR Therapeutics
CRISPR Therapeutics is a leading gene editing company focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. CRISPR/Cas9 is a revolutionary gene editing technology that allows for precise, directed changes to genomic DNA. CRISPR Therapeutics has established a portfolio of therapeutic programs across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine and rare diseases. To accelerate and expand its efforts, CRISPR Therapeutics has established strategic collaborations with leading companies including Bayer, Vertex Pharmaceuticals and ViaCyte, Inc. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations in Boston, Massachusetts and San Francisco, California, and business offices in London, United Kingdom.
Vertex Special Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, the statements by Reshma Kewalramani, M.D., Samarth Kulkarni, Ph.D., and Stephan Grupp, M.D., Ph.D., and statements regarding the anticipated patient population eligible for CASGEVY in the U.S., expectations for the potential benefits of CASGEVY, expectations that additional ATCs will be activated in the coming weeks, Vertex's plan to make milestone payments to CRISPR, and Vertex's anticipated accounting treatment for milestone payments, anticipated revenue, the cost of sales, expenses, and net profits or losses related to CASGEVY. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that data from the company's development programs may not support registration or further development of its compounds due to safety, efficacy or other reasons, that obtaining approval for and commercializing CASGEVY in Europe and the Kingdom of Saudi Arabia may not occur on the anticipated timeline, or at all, and other risks listed under the heading 'Risk Factors' in Vertex's most recent annual report and subsequent filings filed with the Securities and Exchange Commission at www.sec.gov and available through the company's website at www.vrtx.com. You should not place undue reliance on these statements or the scientific data presented. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
CRISPR Therapeutics Forward-Looking Statement
This press release may contain a number of 'forward-looking statements' within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements made by Reshma Kewalramani, M.D., Samarth Kulkarni, Ph.D., and Stephan Grupp, M.D., Ph.D., in this press release, as well as statements regarding CRISPR Therapeutics': (i) plans and expectations for the commercialization of, and anticipated benefits of, CASGEVY, including the anticipated patient population eligible for CASGEVY in the United States and patient access to CASGEVY; (ii) expectations regarding the ongoing exa-cel clinical trials, including potential implications of clinical data for patients; (iii) timelines for and expectations regarding additional regulatory agency decisions; (iv) receipt of the milestone payment from Vertex and (v) expectations regarding the therapeutic value, development, and commercial potential of CRISPR/Cas9 gene editing technologies and therapies. Without limiting the foregoing, the words 'believes,' 'anticipates,' 'plans,' 'expects' and similar expressions are intended to identify forward-looking statements. You are cautioned that forward-looking statements are inherently uncertain. Actual performance and results may differ materially from those projected or suggested in the forward-looking statements due to various risks and uncertainties. These risks and uncertainties include, among others, that: the clinical data from ongoing clinical trials of exa-cel will not continue or be repeated in ongoing or planned clinical trials or may not support regulatory approval or renewal of conditional authorization; regulatory approval in other jurisdictions may not occur on anticipated timelines or at all; adequate pricing or reimbursement may not be secured to support continued development or commercialization of exa-cel following regulatory approval; future competitive or other market factors may adversely affect the commercial potential for CASGEVY; CRISPR Therapeutics may not realize the potential benefits of its collaboration with Vertex; there are uncertainties regarding the intellectual property protection for CRISPR Therapeutics' technology and intellectual property belonging to third parties and those risks and uncertainties described under the heading 'Risk Factors' in CRISPR Therapeutics' most recent annual report on Form 10-K, quarterly report on Form 10-Q, and in any other subsequent filings made by CRISPR Therapeutics with the U.S. Securities and Exchange Commission, which are available on the SEC's website at www.sec.gov. CRISPR Therapeutics disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this press release, other than to the extent required by law.
Contact:
Manisha Pai
Tel: +1 617-961-1899
Email: InvestorInfo@vrtx.com
VERTEX PHARMACEUTICALS INCORPORATED 
