Joint FDA/ASH Led Initiative Highlights Importance of Using Patient Reported Outcomes and Biomarkers in Clinical Trials to Advance SCD Therapies
(WASHINGTON, DC, Dec. 6, 2019) — The American Society of Hematology (ASH) today released the most comprehensive set of recommendations to date aimed at establishing uniformity and global standards for clinical trial endpoints used to evaluate new therapies for sickle cell disease (SCD). The new recommendations – published in two companion papers in the current issue of Blood Advances – are the result of seven expert and patient led panels convened by ASH and the U.S. Food and Drug Administration (FDA) to improve the design of clinical trials for new SCD therapies, including promoting broader use of patient reported outcomes and biomarkers as clinical endpoints.
Sickle cell disease is the most common inherited red blood cell disorder in the United States, and it affects millions of people worldwide. In people living with SCD, the red blood cells, which are normally round, become crescent or sickle-shaped which contributes to the vaso-occlusive crises these patients experience. People with SCD suffer from an array of physical complications, including acute pain crises, joint and organ damage, impaired cognitive function, and a reduced life expectancy. In addition to the immense physical burden they must endure, people with SCD are often stigmatized due to a poor understanding among healthcare professionals and the general public of the life-limiting effects of the disease. Supporting SCD research and access to care efforts for all people living with the disease is a chief priority for ASH.
While the molecular basis of SCD has been well understood for decades, there are currently only four FDA approved treatments for this debilitating condition. Bone marrow transplant is a cure for some individuals with SCD, but it is not an option for everyone. Although two new treatments for SCD have recently been approved, and many others – including potentially curative gene therapies – are in development, medical experts and FDA officials agree there is a need for uniformity around clinical trial endpoints to ensure these new therapies deliver a meaningful benefit from the patient’s perspective. “There are a number of investigational drugs in development that target different manifestations of SCD,” said Julie Panepinto, MD, MSPH, FAAP, Professor of pediatric hematology, Medical College of Wisconsin/Children’s Wisconsin, co-chair of ASH’s Guideline Oversight Committee, and co-chair of the workshop. “However, there are no clear standardized endpoints for evaluating the effect of therapies on clinical outcomes and patient well-being.”
Dr. Panepinto said that amid the burgeoning effort to develop curative SCD therapies, clinical research should incorporate endpoints that are not only measurable, but also relevant and directly beneficial to the patient based on their preferences and experience.
“What’s happening in SCD is really exciting and many of us feel we are on the cusp of identifying multiple disease-modifying therapies,” Dr. Panepinto said. “The field is exploding, so we want to be sure we are measuring relevant endpoints for researchers, clinicians, and patients because that helps us advance the field and get new therapies approved.”
Ann Farrell, MD, Director of the FDA’s Division of Hematology Products and co-chair of the workshop, points out that the scientific understanding and the treatment of SCD have evolved to a point that the endpoints used to evaluate earlier SCD treatments are now inadequate.
“These changes have greatly impacted the discussion the Agency is having with the pharmaceutical industry as new clinical trials are designed,” said Dr. Farrell. “We need endpoints that better reflect the patient experience of their disease in the current healthcare system.”
To address the global burden of SCD, ASH and the FDA convened seven panels of clinicians, investigators, and people with SCD in a two-day workshop to bring uniformity and standards to existing endpoints, identify gaps, and propose development of new endpoints as a focus for future research. Led by Drs. Panepinto and Farrell, the panels conducted extensive literature reviews, assessed available evidence, and used expert judgement to identify which existing endpoints can be incorporated into SCD clinical trials and what additional data are needed. The panels focused on the following areas:
· Patient reported outcomes (PROs) – the panel suggested that future trials should measure the impact in three key domains: crisis and non-crisis pain; affect (including emotional impact, sleep quality and fatigue), and function (social, physical and cognitive),
· Pain (non-PROs) – this panel recommended measuring healthcare utilization, analgesic use, and physical function as a complementary measure to PROs on pain,
· The brain – the panel reviewed and identified diagnostic modalities to assess neurological risk, document stroke, and measure cognition and educational attainment,
· End-organ considerations – the panel stressed the need to use biomarkers and endpoints that capture the progression of renal and cardiopulmonary disease,
· Biomarkers – this panel overlapped with other panels addressing various disease manifestations, highlighting the importance of developing and validating a broader array of biomarkers that can measure response to therapy,
· Measurements of cure – given this is a relatively new area of research, the panel identified the need to develop appropriate biomarkers to evaluate the effect of curative therapies, and to capture and share these data in a central repository to help advance the scientific understanding and broader use of these treatments,
· Care in low-resource settings – this panel noted an opportunity to accelerate clinical trials in regions with a high prevalence of SCD, such as sub-Saharan Africa. They also recommended capturing data on early childhood, peri-operative and pregnancy-related mortality, as well as PROs from children and their caregivers relating to growth and development.
The published recommendations represent the most comprehensive review of science to date in the treatment of SCD and will be a valuable reference for academic researchers seeking funding for scientific studies and pharmaceutical companies looking to identify endpoints for specific clinical trials.
“The papers document the wide-ranging discussions held by researchers, patients, caregivers, international experts, pharmaceutical industry and government to understand where we are in terms of defining clinical trial endpoints for current use and those for future development that will serve patients best,” said Dr. Farrell. She also noted the initiative identified several opportunities to incorporate the patient voice in clinical practice to help better understand how effective current medical treatments are.
The workshop was modeled after an earlier ASH/FDA initiative that focused on leukemia and myeloma, and was generously supported solely by the philanthropic support from numerous individual donors who contributed to the ASH Foundation’s Sickle Cell Disease Initiative Fund and by the Doris Duke Charitable Foundation.
In 2016, ASH launched a multifaceted initiative to address the burden of disease both in the United States and globally. For this initiative, ASH has developed clinical guidelines for SCD management and care, expanded education and training efforts, advocated with policymakers to enhance and expand federal SCD programs, and founded the Sickle Cell Disease Coalition. In addition to these efforts, the ASH Research Collaborative (ASH RC) SCD Clinical Trials Network was developed with the mission to improve outcomes for individuals with SCD by expediting SCD therapy development and facilitating innovation in clinical trial research. It provides the infrastructure for identifying patient cohorts for trials, matching trial sponsors with sites, facilitating recruitment of eligible patients, and ensuring optimally designed trials and an efficient, coordinated approach. Through patient engagement and optimized clinical trial execution, the Clinical Trials Network is helping to bring new and more effective therapies to individuals with SCD.
Papers in Blood Advances:
· End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain
· End points for sickle cell disease clinical trials: renal and cardiopulmonary, cure, and low-resource setting
The American Society of Hematology (ASH) (www.hematology.org) is the world’s largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 60 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. ASH publishes Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field, and Blood Advances (www.bloodadvances.org), an online, peer-reviewed open-access journal.
Category Archives: News
GBT’s Oxbryta™ (voxelotor) tablets is approved for the treatment of sickle cell disease
Oxbryta™ (voxelotor) tablets Now Approved
On behalf of GBT, we are happy to share that Oxbryta (pronounced ox-brye-ta) is now approved by the U.S. Food and Drug Administration (FDA). Oxbryta is a prescription medicine used for the treatment of sickle cell disease in adults and children 12 years of age and older.1 It is not known if Oxbryta is safe and effective in children below 12 years of age.1
This indication is approved under accelerated approval based on increase in hemoglobin (Hb). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).2
This approval has been the result of years of collaboration with the community, and we are so grateful for your role in helping GBT get this to patients quickly!
1) Oxbryta is the brand name for voxelotor. This approval represents a historic one, as Oxbryta is the first sickle cell disease drug approved under both the Breakthrough Therapy and Accelerated Approval designations by the FDA.
· Voxelotor is a hemoglobin S (HbS) polymerization inhibitor.2
· Nonclinical studies suggest that voxelotor may inhibit red blood cell (RBC) sickling, improve RBC deformability, and reduce whole blood viscosity.2
· It is a prescription medicine (tablet) taken by mouth once daily, every day.1
2) Oxbryta should not be taken if a patient has had an allergic reaction to voxelotor or any of the ingredients in Oxbryta. Oxbryta can cause side effects including: headache, diarrhea, stomach (abdominal) pain, nausea, tiredness, rash and fever.1
Patient Support: GBT Source Solutions™
As part of GBT’s commitment to supporting access to care for patients, we have launched GBT Source Solutions, a resource center for patients who have been prescribed Oxbryta by their healthcare provider. GBT Source Solutions will provide support by:
· Reviewing insurance coverage options and explaining benefits.
· Coordinating shipment of Oxbryta and explaining Specialty Pharmacy benefits.
· Helping to pay for treatment with financial and co-pay assistance for eligible patients.
· Helping to stay on treatment with a nurse support team. The nurse support team is there to support product adherence, and not to replace a patient’s treatment plan. They do not provide medical advice or case management services.
Your role
Your organization plays a critical role in supporting patients, and we are very thankful for everything you do for people living with SCD. Your collaboration is critical to helping inform patients about Oxbryta and GBT’s patient support services for patients prescribed Oxbryta.
If a patient is interested in learning more about Oxbryta, they should consult their healthcare professional or visit www.Oxbryta.com.
We have attached in this email several resources. You may share these with patients, caregivers, and other members of your community.
… Oxbryta fact sheet
… Oxbryta patient education brochure
… GBT Source Solutions brochure
Please feel free to reach out with any questions. We look forward to continuing our collaboration to help improve the lives of SCD patients and provide hope to our community.
Warmest regards,
Jung
INDICATION AND IMPORTANT SAFETY INFORMATION
INDICATION
What is OXBRYTA?
OXBRYTA is a prescription medicine used for the treatment of sickle cell disease in adults and children 12 years of age and older.
It is not known if OXBRYTA is safe and effective in children below 12 years of age.
This indication is approved under accelerated approval based on increase in hemoglobin (Hb). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
IMPORTANT SAFETY INFORMATION
Do not take OXBRYTA if you have had an allergic reaction to voxelotor or any of the ingredients in OXBRYTA. See the end of the patient leaflet for a list of the ingredients in OXBRYTA.
If you are receiving exchange transfusions, talk to your healthcare provider about possible difficulties with the interpretation of certain blood tests when taking OXBRYTA.
Before taking OXBRYTA, tell your healthcare provider about all of your medical conditions, including if you:
· have liver problems
· are pregnant or plan to become pregnant. It is not known if OXBRYTA can harm your unborn baby.
· are breastfeeding or plan to breastfeed. It is not known if OXBRYTA can pass into your breastmilk and if it can harm your baby. Do not breastfeed during treatment with OXBRYTA and for at least 2 weeks after the last dose.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some medicines may affect how OXBRYTA works. OXBRYTA may also affect how other medicines work.
What are the possible side effects of OXBRYTA?
OXBRYTA can cause serious side effects, including:
Serious allergic reactions. Tell your healthcare provider or get emergency medical help right away if you get:
· rash
· hives
· shortness of breath
· swelling of the face
The most common side effects of OXBRYTA include:
· headache
· diarrhea
· stomach (abdominal) pain
· nausea
· tiredness
· rash
· fever
These are not all the possible side effects of OXBRYTA.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
You may also report side effects to Global Blood Therapeutics at 1-833-428-4968 (1-833-GBT-4YOU).
Keep OXBRYTA and all medicines out of the reach of children.
1 Patient Information Leaflet 11 2019
2 USPI 11 2019
CRISPR Therapeutics and Vertex Announce Positive Safety and Efficacy Data
Nov 19, 2019
CRISPR Therapeutics and Vertex Announce Positive Safety and Efficacy Data From First Two Patients Treated With Investigational CRISPR/Cas9 Gene-Editing Therapy CTX001® for Severe Hemoglobinopathies
-Two patients treated with CTX001 successfully engrafted and demonstrated an initial safety profile consistent with myeloablative busulfan conditioning and autologous hematopoietic stem cell transplant-
-Beta thalassemia: Patient is transfusion independent with total hemoglobin level of 11.9 g/dL and 10.1 g/dL fetal hemoglobin at nine months after CTX001 infusion-
-Sickle cell disease: Patient is free of vaso-occlusive crises with total hemoglobin level of 11.3 g/dL and 46.6% fetal hemoglobin at four months after CTX001 infusion-
-CRISPR Therapeutics will host a conference call today at 8:00 a.m. ET to review these data-
ZUG, Switzerland and CAMBRIDGE, Mass. and BOSTON, Nov. 19, 2019 (GLOBE NEWSWIRE) — CRISPR Therapeutics (NASDAQ: CRSP) and Vertex Pharmaceuticals Incorporated (NASDAQ: VRTX) today announced positive, interim data from the first two patients with severe hemoglobinopathies treated with the investigational CRISPR/Cas9 gene-editing therapy CTX001 in ongoing Phase 1/2 clinical trials. One patient with transfusion-dependent beta thalassemia (TDT) received CTX001 in the first quarter of 2019 and data for this patient reflect nine months of safety and efficacy follow-up. One patient with severe sickle cell disease (SCD) received CTX001 in mid-2019 and data for this patient reflect four months of safety and efficacy follow-up. These studies are ongoing and patients will be followed for approximately two years following infusion. Several additional patients have been enrolled and have had drug product manufactured across the two studies.
Transfusion-Dependent Beta Thalassemia
The patient with TDT has the β0/IVS-I-110 genotype and required 16.5 transfusions per year (annualized rate during the two years prior to consenting for the study) before enrolling in the clinical study. The patient achieved neutrophil engraftment 33 days after CTX001 infusion and platelet engraftment 37 days after infusion. Two serious adverse events (SAEs) occurred, neither of which the principal investigator (PI) considered related to CTX001: pneumonia in the presence of neutropenia and veno-occlusive liver disease attributed to busulfan conditioning; both subsequently resolved. At nine months after CTX001 infusion, the patient was transfusion independent and had total hemoglobin levels of 11.9 g/dL, 10.1 g/dL fetal hemoglobin, and 99.8% F-cells (erythrocytes expressing fetal hemoglobin).
Sickle Cell Disease
The patient with SCD experienced seven vaso-occlusive crises (VOCs) per year (annualized rate during the two years prior to consenting for the study) before enrolling in the clinical study. The patient achieved neutrophil and platelet engraftment 30 days after CTX001 infusion. Three SAEs occurred, none of which the PI considered related to CTX001: sepsis in the presence of neutropenia, cholelithiasis, and abdominal pain, all of which resolved. At four months after CTX001 infusion, the patient was free of VOCs and had total hemoglobin levels of 11.3 g/dL, 46.6% fetal hemoglobin, and 94.7% F-cells (erythrocytes expressing fetal hemoglobin).
“We are very encouraged by these preliminary data, the first such data to be reported for patients with beta thalassemia and sickle cell disease treated with our CRISPR/Cas9 edited autologous hematopoietic stem cell candidate, CTX001,” said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. “These data support our belief in the potential of our therapies to have meaningful benefit for patients following a one-time intervention. We continue to enroll these studies as we drive forward to develop CRISPR/Cas9 therapies as a new class of transformative medicines to treat serious diseases.”
“The data we announced today are remarkable and demonstrate that CTX001 has the potential to be a curative CRISPR/Cas9-based gene-editing therapy for people with sickle cell disease and beta thalassemia,” said Jeffrey Leiden, M.D., Ph.D., Chairman, President and Chief Executive Officer of Vertex. “While the data are exciting, we are still in the early phase of this clinical program. We look forward to continuing to work with physicians, patients, caregivers and families over the coming months and years to bring forward the best possible therapy for these two serious diseases and to continue to accelerate our gene-editing programs for other serious diseases such as Duchenne muscular dystrophy and myotonic dystrophy type 1.”
About the Phase 1/2 Study in Transfusion-Dependent Beta Thalassemia
The ongoing Phase 1/2 open-label trial, CLIMB-Thal-111, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 18 to 35 with TDT. The study will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up study. Enrollment is ongoing at six clinical trial sites in the United States, Canada and Europe.
About the Phase 1/2 Study in Sickle Cell Disease
The ongoing Phase 1/2 open-label trial, CLIMB-SCD-121, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 18 to 35 with severe SCD. The study will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up study. Enrollment is ongoing at 12 clinical trial sites in the United States, Canada and Europe.
About the Gene–Editing Process in These Trials
Patients who enroll in these studies will have hematopoietic stem and progenitor cells collected from peripheral blood. The patient’s cells will be edited using the CRISPR/Cas9 technology. The edited cells, CTX001, will then be infused back into the patient as part of a stem cell transplant, a process which involves, among other things, a patient being treated with myeloablative busulfan conditioning. Patients undergoing stem cell transplants may also encounter side effects (ranging from mild to severe) that are unrelated to the administration of CTX001. Patients will initially be monitored to determine when the edited cells begin to produce mature blood cells, a process known as engraftment. After engraftment, patients will continue to be monitored to track the impact of CTX001 on multiple measures of disease.
CRISPR Therapeutics Conference Call and Webcast
CRISPR Therapeutics will host a conference call and webcast today at 8:00 a.m. ET. The webcast and presentation will be made available on the CRISPR Therapeutics website at https://crisprtx.gcs-web.com/events in the Investors section under Events and Presentations. Following the live audio webcast, a replay will be available on the Company’s website for approximately 30 days.
Dial-In Information
Live (U.S. / Canada): (800) 895-3361
Live (International): (785) 424-1062
Conference ID: 87198237
About CTX001
CTX001 is an investigational ex vivo CRISPR gene-edited therapy that is being evaluated for patients suffering from TDT or severe SCD in which a patient’s hematopoietic stem cells are engineered to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth and is then replaced by the adult form of hemoglobin. The elevation of HbF by CTX001 has the potential to alleviate transfusion requirements for TDT patients and painful and debilitating sickle crises for SCD patients.
CTX001 is being developed under a co-development and co-commercialization agreement between CRISPR Therapeutics and Vertex.
About the CRISPR-Vertex Collaboration
CRISPR Therapeutics and Vertex entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. CTX001 represents the first treatment to emerge from the joint research program. CRISPR Therapeutics and Vertex will jointly develop and commercialize CTX001 and equally share all research and development costs and profits worldwide.
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 AG, 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 based in Cambridge, Massachusetts, and business offices in London, United Kingdom. For more information, please visit www.crisprtx.com.
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 regarding CRISPR Therapeutics’ expectations about any or all of the following: (i) the safety, efficacy and clinical progress of CRISPR Therapeutics’ CTX001 clinical program; (ii) the status and scope of ongoing and potential future clinical trials (including, without limitation, the timing of filing of clinical trial applications and INDs, any approvals thereof and the timing of commencement of clinical trials), development timelines and discussions with regulatory authorities related to product candidates under development by CRISPR Therapeutics and its collaborators; (iii) the number of patients that will be evaluated, the anticipated date by which enrollment will be completed and the data that will be generated by ongoing and planned clinical trials, and the ability to use that data for the design and initiation of further clinical trials; v(iv) the intellectual property coverage and positions of CRISPR Therapeutics, its licensors and third parties; (v) the sufficiency of CRISPR Therapeutics’ cash resources; and (vi) 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. Although CRISPR Therapeutics believes that such statements are based on reasonable assumptions within the bounds of its knowledge of its business and operations, forward-looking statements are neither promises nor guarantees and they are necessarily subject to a high degree of uncertainty and risk. 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: the potential for initial and preliminary data from any clinical trial (including CTX001) not to be indicative of final trial results; the risk that the initial data from a limited number of patients (as is the case with CTX001 at this time) may not be indicative of results from the full planned study population; the outcomes for each CRISPR Therapeutics’ planned clinical trials and studies may not be favorable; that one or more of CRISPR Therapeutics’ internal or external product candidate programs will not proceed as planned for technical, scientific or commercial reasons; that future competitive or other market factors may adversely affect the commercial potential for CRISPR Therapeutics’ product candidates; uncertainties inherent in the initiation and completion of preclinical studies for CRISPR Therapeutics’ product candidates; availability and timing of results from preclinical studies; whether results from a preclinical trial will be predictive of future results of the future trials; uncertainties about regulatory approvals to conduct trials or to market products; uncertainties regarding the intellectual property protection for CRISPR Therapeutics’ technology and intellectual property belonging to third parties, and the outcome of proceedings (such as an interference, an opposition or a similar proceeding) involving all or any portion of such intellectual property; and those risks and uncertainties described under the heading “Risk Factors” in CRISPR Therapeutics’ most recent annual report on Form 10-K, 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. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date they are made. 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.
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 four approved medicines that treat the underlying cause of cystic fibrosis (CF) — a rare, life-threatening genetic disease — and has several ongoing clinical and research programs in CF. Beyond CF, Vertex has a robust pipeline of investigational small molecule medicines in other serious diseases where it has deep insight into causal human biology, including pain, alpha-1 antitrypsin deficiency, and APOL1-mediated kidney disease. In addition, Vertex has a rapidly expanding pipeline of genetic and cell therapies for diseases such as sickle cell disease, beta thalassemia, Duchenne muscular dystrophy and type 1 diabetes mellitus.
Founded in 1989 in Cambridge, Mass., Vertex’s global headquarters is now located in Boston’sInnovation District and its international headquarters is in London, UK. 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 10 consecutive years on Science magazine’s Top Employers list and top five on the 2019 Best Employers for Diversity list by Forbes. For company updates and to learn more about Vertex’s history of innovation, visit www.vrtx.com or follow us on Facebook, Twitter, LinkedIn, YouTube and Instagram.
(VRTX-GEN)
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, including, without limitation, the information provided regarding the status of, and expectations with respect to, the CTX001 clinical development program. 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 factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include that the development of CTX001 may not proceed due to safety, efficacy or other reasons, and other risks listed under Risk Factors in Vertex’s annual report and quarterly reports filed with the Securities and Exchange Commission and available through the company’s website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
CRISPR Therapeutics Investor Contact:
Susan Kim, +1 617-307-7503
susan.kim@crisprtx.com
CRISPR Therapeutics Media Contact:
Jennifer Paganelli
WCG on behalf of CRISPR
+1 347-658-8290
jpaganelli@wcgworld.com
Vertex Pharmaceuticals Incorporated
Investors:
Michael Partridge, +1 617-341-6108
or
Zach Barber, +1 617-341-6470
or
Leah Gibson, +1 617-961-1507
Media: mediainfo@vrtx.com
or
North America:
Heather Nichols, +1 617-341-6992
Heather_Nichols@vrtx.com
-Beta thalassemia: Patient is transfusion independent with total hemoglobin level of 11.9 g/dL and 10.1 g/dL fetal hemoglobin at nine months after CTX001 infusion-
-Sickle cell disease: Patient is free of vaso-occlusive crises with total hemoglobin level of 11.3 g/dL and 46.6% fetal hemoglobin at four months after CTX001 infusion-
-CRISPR Therapeutics will host a conference call today at 8:00 a.m. ET to review these data-
ZUG, Switzerland and CAMBRIDGE, Mass. and BOSTON, Nov. 19, 2019 (GLOBE NEWSWIRE) — CRISPR Therapeutics (NASDAQ: CRSP) and Vertex Pharmaceuticals Incorporated (NASDAQ: VRTX) today announced positive, interim data from the first two patients with severe hemoglobinopathies treated with the investigational CRISPR/Cas9 gene-editing therapy CTX001 in ongoing Phase 1/2 clinical trials. One patient with transfusion-dependent beta thalassemia (TDT) received CTX001 in the first quarter of 2019 and data for this patient reflect nine months of safety and efficacy follow-up. One patient with severe sickle cell disease (SCD) received CTX001 in mid-2019 and data for this patient reflect four months of safety and efficacy follow-up. These studies are ongoing and patients will be followed for approximately two years following infusion. Several additional patients have been enrolled and have had drug product manufactured across the two studies.
Transfusion-Dependent Beta Thalassemia
The patient with TDT has the β0/IVS-I-110 genotype and required 16.5 transfusions per year (annualized rate during the two years prior to consenting for the study) before enrolling in the clinical study. The patient achieved neutrophil engraftment 33 days after CTX001 infusion and platelet engraftment 37 days after infusion. Two serious adverse events (SAEs) occurred, neither of which the principal investigator (PI) considered related to CTX001: pneumonia in the presence of neutropenia and veno-occlusive liver disease attributed to busulfan conditioning; both subsequently resolved. At nine months after CTX001 infusion, the patient was transfusion independent and had total hemoglobin levels of 11.9 g/dL, 10.1 g/dL fetal hemoglobin, and 99.8% F-cells (erythrocytes expressing fetal hemoglobin).
Sickle Cell Disease
The patient with SCD experienced seven vaso-occlusive crises (VOCs) per year (annualized rate during the two years prior to consenting for the study) before enrolling in the clinical study. The patient achieved neutrophil and platelet engraftment 30 days after CTX001 infusion. Three SAEs occurred, none of which the PI considered related to CTX001: sepsis in the presence of neutropenia, cholelithiasis, and abdominal pain, all of which resolved. At four months after CTX001 infusion, the patient was free of VOCs and had total hemoglobin levels of 11.3 g/dL, 46.6% fetal hemoglobin, and 94.7% F-cells (erythrocytes expressing fetal hemoglobin).
“We are very encouraged by these preliminary data, the first such data to be reported for patients with beta thalassemia and sickle cell disease treated with our CRISPR/Cas9 edited autologous hematopoietic stem cell candidate, CTX001,” said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. “These data support our belief in the potential of our therapies to have meaningful benefit for patients following a one-time intervention. We continue to enroll these studies as we drive forward to develop CRISPR/Cas9 therapies as a new class of transformative medicines to treat serious diseases.”
“The data we announced today are remarkable and demonstrate that CTX001 has the potential to be a curative CRISPR/Cas9-based gene-editing therapy for people with sickle cell disease and beta thalassemia,” said Jeffrey Leiden, M.D., Ph.D., Chairman, President and Chief Executive Officer of Vertex. “While the data are exciting, we are still in the early phase of this clinical program. We look forward to continuing to work with physicians, patients, caregivers and families over the coming months and years to bring forward the best possible therapy for these two serious diseases and to continue to accelerate our gene-editing programs for other serious diseases such as Duchenne muscular dystrophy and myotonic dystrophy type 1.”
About the Phase 1/2 Study in Transfusion-Dependent Beta Thalassemia
The ongoing Phase 1/2 open-label trial, CLIMB-Thal-111, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 18 to 35 with TDT. The study will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up study. Enrollment is ongoing at six clinical trial sites in the United States, Canada and Europe.
About the Phase 1/2 Study in Sickle Cell Disease
The ongoing Phase 1/2 open-label trial, CLIMB-SCD-121, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 18 to 35 with severe SCD. The study will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up study. Enrollment is ongoing at 12 clinical trial sites in the United States, Canada and Europe.
About the Gene–Editing Process in These Trials
Patients who enroll in these studies will have hematopoietic stem and progenitor cells collected from peripheral blood. The patient’s cells will be edited using the CRISPR/Cas9 technology. The edited cells, CTX001, will then be infused back into the patient as part of a stem cell transplant, a process which involves, among other things, a patient being treated with myeloablative busulfan conditioning. Patients undergoing stem cell transplants may also encounter side effects (ranging from mild to severe) that are unrelated to the administration of CTX001. Patients will initially be monitored to determine when the edited cells begin to produce mature blood cells, a process known as engraftment. After engraftment, patients will continue to be monitored to track the impact of CTX001 on multiple measures of disease.
CRISPR Therapeutics Conference Call and Webcast
CRISPR Therapeutics will host a conference call and webcast today at 8:00 a.m. ET. The webcast and presentation will be made available on the CRISPR Therapeutics website at https://crisprtx.gcs-web.com/events in the Investors section under Events and Presentations. Following the live audio webcast, a replay will be available on the Company’s website for approximately 30 days.
Dial-In Information
Live (U.S. / Canada): (800) 895-3361
Live (International): (785) 424-1062
Conference ID: 87198237
About CTX001
CTX001 is an investigational ex vivo CRISPR gene-edited therapy that is being evaluated for patients suffering from TDT or severe SCD in which a patient’s hematopoietic stem cells are engineered to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth and is then replaced by the adult form of hemoglobin. The elevation of HbF by CTX001 has the potential to alleviate transfusion requirements for TDT patients and painful and debilitating sickle crises for SCD patients.
CTX001 is being developed under a co-development and co-commercialization agreement between CRISPR Therapeutics and Vertex.
About the CRISPR-Vertex Collaboration
CRISPR Therapeutics and Vertex entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. CTX001 represents the first treatment to emerge from the joint research program. CRISPR Therapeutics and Vertex will jointly develop and commercialize CTX001 and equally share all research and development costs and profits worldwide.
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 AG, 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 based in Cambridge, Massachusetts, and business offices in London, United Kingdom. For more information, please visit www.crisprtx.com.
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 regarding CRISPR Therapeutics’ expectations about any or all of the following: (i) the safety, efficacy and clinical progress of CRISPR Therapeutics’ CTX001 clinical program; (ii) the status and scope of ongoing and potential future clinical trials (including, without limitation, the timing of filing of clinical trial applications and INDs, any approvals thereof and the timing of commencement of clinical trials), development timelines and discussions with regulatory authorities related to product candidates under development by CRISPR Therapeutics and its collaborators; (iii) the number of patients that will be evaluated, the anticipated date by which enrollment will be completed and the data that will be generated by ongoing and planned clinical trials, and the ability to use that data for the design and initiation of further clinical trials; v(iv) the intellectual property coverage and positions of CRISPR Therapeutics, its licensors and third parties; (v) the sufficiency of CRISPR Therapeutics’ cash resources; and (vi) 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. Although CRISPR Therapeutics believes that such statements are based on reasonable assumptions within the bounds of its knowledge of its business and operations, forward-looking statements are neither promises nor guarantees and they are necessarily subject to a high degree of uncertainty and risk. 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: the potential for initial and preliminary data from any clinical trial (including CTX001) not to be indicative of final trial results; the risk that the initial data from a limited number of patients (as is the case with CTX001 at this time) may not be indicative of results from the full planned study population; the outcomes for each CRISPR Therapeutics’ planned clinical trials and studies may not be favorable; that one or more of CRISPR Therapeutics’ internal or external product candidate programs will not proceed as planned for technical, scientific or commercial reasons; that future competitive or other market factors may adversely affect the commercial potential for CRISPR Therapeutics’ product candidates; uncertainties inherent in the initiation and completion of preclinical studies for CRISPR Therapeutics’ product candidates; availability and timing of results from preclinical studies; whether results from a preclinical trial will be predictive of future results of the future trials; uncertainties about regulatory approvals to conduct trials or to market products; uncertainties regarding the intellectual property protection for CRISPR Therapeutics’ technology and intellectual property belonging to third parties, and the outcome of proceedings (such as an interference, an opposition or a similar proceeding) involving all or any portion of such intellectual property; and those risks and uncertainties described under the heading “Risk Factors” in CRISPR Therapeutics’ most recent annual report on Form 10-K, 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. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date they are made. 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.
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 four approved medicines that treat the underlying cause of cystic fibrosis (CF) — a rare, life-threatening genetic disease — and has several ongoing clinical and research programs in CF. Beyond CF, Vertex has a robust pipeline of investigational small molecule medicines in other serious diseases where it has deep insight into causal human biology, including pain, alpha-1 antitrypsin deficiency, and APOL1-mediated kidney disease. In addition, Vertex has a rapidly expanding pipeline of genetic and cell therapies for diseases such as sickle cell disease, beta thalassemia, Duchenne muscular dystrophy and type 1 diabetes mellitus.
Founded in 1989 in Cambridge, Mass., Vertex’s global headquarters is now located in Boston’sInnovation District and its international headquarters is in London, UK. 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 10 consecutive years on Science magazine’s Top Employers list and top five on the 2019 Best Employers for Diversity list by Forbes. For company updates and to learn more about Vertex’s history of innovation, visit www.vrtx.com or follow us on Facebook, Twitter, LinkedIn, YouTube and Instagram.
(VRTX-GEN)
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, including, without limitation, the information provided regarding the status of, and expectations with respect to, the CTX001 clinical development program. 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 factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include that the development of CTX001 may not proceed due to safety, efficacy or other reasons, and other risks listed under Risk Factors in Vertex’s annual report and quarterly reports filed with the Securities and Exchange Commission and available through the company’s website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
CRISPR Therapeutics Investor Contact:
Susan Kim, +1 617-307-7503
susan.kim@crisprtx.com
CRISPR Therapeutics Media Contact:
Jennifer Paganelli
WCG on behalf of CRISPR
+1 347-658-8290
jpaganelli@wcgworld.com
Vertex Pharmaceuticals Incorporated
Investors:
Michael Partridge, +1 617-341-6108
or
Zach Barber, +1 617-341-6470
or
Leah Gibson, +1 617-961-1507
Media: mediainfo@vrtx.com
or
North America:
Heather Nichols, +1 617-341-6992
Heather_Nichols@vrtx.com