giroctocogene fitelparvovec (SB-525) / Sangamo Therap - LARVOL DELTA

BENEGENE-1: A Study to Evaluate Prospective Efficacy and Safety Data of Current FIX Prophylaxis Replacement Therapy in Adult Hemophilia B Subjects (FIX:C≤2%) or Current FVIII Prophylaxis Replacement Therapy in Adult Hemophilia A Subjects (FVIII:C≤1%) (clinicaltrials.gov) - P3 | N=213 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed

Trial completion • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

Sangamo Therapeutics to Regain Full Rights to Hemophilia A Gene Therapy Program Following Pfizer’s Decision to Cease Development of Giroctocogene Fitelparvovec (Businesswire) - "Sangamo Therapeutics...announced it will regain development and commercialization rights to giroctocogene fitelparvovec, an investigational gene therapy product candidate for the treatment of adults with moderately severe to severe hemophilia A that it has co-developed with, and licensed to Pfizer Inc., following a decision by Pfizer to terminate the global collaboration and license agreement between the parties. Sangamo intends to explore all options to advance the program, including seeking a potential new collaboration partner. Pfizer has indicated to Sangamo that this termination reflects its decision not to proceed with the...BLA and Marketing Authorisation Application (MAA) submissions for, or to pursue commercialization of, giroctocogene fitelparvovec....The collaboration and license agreement with Pfizer will terminate effective April 21, 2025, at which time Pfizer will be required to transition the giroctocogene fitelparvovec program back to Sangamo."

Licensing / partnership • Hemophilia A

Results from the Hemophilia Α Cohort of the Non-Investigational Lead-in Study: Prospective Collection of Bleeding Rate in Participants with Hemophilia Α Prior to Phase 3 Study (AFFINE) of Giroctocogene Fitelparvovec (ASH 2024) - P3 | "Introduction : Giroctocogene fitelparvovec (PF-07055480) is a liver-directed recombinant adeno-associated virus serotype 6 (AAV6) gene therapy vector encoding a B-domain–deleted variant of human factor VIII (FVIII) that enables sustained endogenous FVIII expression...Although FVIII prophylaxis was well tolerated, with no emerging safety signals, a total ABR of 6.1 illustrates the limitations of current standard of care prophylaxis. The total ABR reported in a subset of participants who went on to enroll in the phase 3 AFFINE trial of giroctocogene fitelparvovec will be used as the comparator for the primary endpoint evaluating noninferiority post gene therapy, in accordance with the AFFINE trial protocol."

Clinical • P3 data • B Cell Lymphoma • Gastroenterology • Gastrointestinal Disorder • Gene Therapies • Hematological Disorders • Hematological Malignancies • Hemophilia • Hemophilia A • Hemophilia B • Immunology • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Rare Diseases

Efficacy and Safety of Giroctocogene Fitelparvovec in Adults with Moderately Severe to Severe Hemophilia Α: Primary Analysis Results from the Phase 3 ΑFFINE Gene Therapy Trial (ASH 2024) - P3 | "Background Giroctocogene fitelparvovec (PF-07055480), a hepatocyte-directed recombinant AAV serotype 6 vector encoding a B-domain–deleted variant of human factor VIII (FVIII), is a single-dose gene therapy aimed at enabling sustained endogenous FVIII expression in individuals with hemophilia A (HA)...Conclusions Giroctocogene fitelparvovec yielded endogenous FVIII expression in the mild to normal range in most participants, and resulted in superior bleed protection vs routine FVIII prophylaxis and significant reductions in bleeding. A single infusion was well tolerated and demonstrated durable efficacy on all primary and key secondary endpoints."

Clinical • Gene therapy • P3 data • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Pain • Rare Diseases

Sangamo Therapeutics Reports Recent Business Highlights and Third Quarter 2024 Financial Results (Businesswire) - P3 | N=76 | AFFINE (NCT04370054) | Sponsor: Pfizer | "Pfizer will be presenting detailed data from the Phase 3 AFFINE trial of giroctocogene fitelparvovec, an investigational gene therapy that Sangamo has co-developed with and licensed to Pfizer for the treatment of adults with moderately severe to severe hemophilia A, in an oral presentation at the 66th ASH Annual Meeting and Exposition on December 9, 2024. The ASH abstract confirmed that the AFFINE trial met its primary endpoint of non-inferiority and superiority, with a statistically significant decrease in total annualized bleeding rate (ABR) from Week 12 through at least 15 months of follow up post-infusion compared with routine Factor VIII (FVIII) replacement prophylaxis treatment (mean total ABR estimates, 1.24 vs 4.73)."

P3 data • Gene Therapies • Genetic Disorders • Hemophilia • Hemophilia A

Alta: A Study of Recombinant AAV2/6 Human Factor 8 Gene Therapy SB-525 (PF-07055480) in Subjects With Severe Hemophilia A (clinicaltrials.gov) - P2 | N=13 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed

Gene therapy • Trial completion • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

BENEGENE-1: A Study to Evaluate Prospective Efficacy and Safety Data of Current FIX Prophylaxis Replacement Therapy in Adult Hemophilia B Subjects (FIX:C≤2%) or Current FVIII Prophylaxis Replacement Therapy in Adult Hemophilia A Subjects (FVIII:C≤1%) (clinicaltrials.gov) - P3 | N=213 | Active, not recruiting | Sponsor: Pfizer | Trial completion date: Feb 2024 ➔ May 2024 | Trial primary completion date: Feb 2024 ➔ May 2024

Gene therapy • Trial completion date • Trial primary completion date • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Four-Year Follow-up of the Alta Study, a Phase 1/2 Study of Giroctocogene Fitelparvovec (PF-07055480/SB-525) Gene Therapy in Adults with Severe Hemophilia Α (ASH 2023) - P2, P3 | "A single infusion of giroctocogene fitelparvovec gene therapy in participants with severe hemophilia A remains generally well tolerated over a period of nearly 4 years post infusion, with associated increases in FVIII levels in the moderate to normal range, without sustained AEs and with no AEs associated with increased liver function tests since Week 59. The ongoing phase 3 study (NCT04370054) in a larger cohort will provide more long-term data on the safety and durability of giroctocogene fitelparvovec in participants with moderately severe to severe hemophilia A."

Clinical • Gene therapy • P1/2 data • Cardiovascular • Gene Therapies • Hematological Disorders • Hemophilia • Hypotension • Rare Diseases

AFFINE: Study to Evaluate the Efficacy and Safety of PF-07055480 / Giroctocogene Fitelparvovec Gene Therapy in Moderately Severe to Severe Hemophilia A Adults (clinicaltrials.gov) - P3 | N=59 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting

Enrollment closed • Gene therapy • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases • CD4

NAB PROTOCOL: A Study to Evaluate Prospective Efficacy and Safety Data of Current FIX Prophylaxis Replacement Therapy in Adult Hemophilia B Subjects (FIX:C≤2%) or Current FVIII Prophylaxis Replacement Therapy in Adult Hemophilia A Subjects (FVIII:C≤1%) (clinicaltrials.gov) - P3 | N=213 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting

Enrollment closed • Gene therapy • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Sangamo Therapeutics Announces Strategic Update and Reports Preliminary First Quarter 2023 Financial Results (Businesswire) - "Dosed third patient in cohort 1 in the Phase 1/2 STEADFAST study evaluating TX200, our wholly owned autologous CAR-Treg cell therapy treating patients receiving an HLA-A2 mismatched kidney from a living donor...Plan to share initial data from cohort 1 by the end of 2023; Dosing of patients to support primary analysis is complete in the Phase 3 AFFINE trial of giroctocogene fitelparvovec, an investigational gene therapy we are developing with Pfizer for patients with moderately severe to severe hemophilia A. A pivotal readout is expected in mid-2024, with Pfizer anticipating BLA and MAA submissions in the second half of 2024."

BLA • European regulatory • P1/2 data • Genetic Disorders • Immunology

NAB PROTOCOL: A Study to Evaluate Prospective Efficacy and Safety Data of Current FIX Prophylaxis Replacement Therapy in Adult Hemophilia B Subjects (FIX:C≤2%) or Current FVIII Prophylaxis Replacement Therapy in Adult Hemophilia A Subjects (FVIII:C≤1%) (clinicaltrials.gov) - P3 | N=250 | Recruiting | Sponsor: Pfizer | Trial completion date: Nov 2023 ➔ Mar 2024 | Trial primary completion date: Nov 2023 ➔ Mar 2024

Gene therapy • Trial completion date • Trial primary completion date • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

AFFINE: Study to Evaluate the Efficacy and Safety of PF-07055480 / Giroctocogene Fitelparvovec Gene Therapy in Moderately Severe to Severe Hemophilia A Adults (clinicaltrials.gov) - P3 | N=63 | Recruiting | Sponsor: Pfizer | Trial completion date: Feb 2028 ➔ Jul 2028

Gene therapy • Trial completion date • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases • CD4

Updated Results of the Alta Study, a Phase 1/2 Study of Giroctocogene Fitelparvovec (PF-07055480/SB-525) Gene Therapy in Adults with Severe Hemophilia Α (ASH 2022) - P2, P3 | "A single infusion of giroctocogene fitelparvovec gene therapy in participants with severe hemophilia A remains generally well tolerated over a period of nearly 3 years postinfusion, with associated increases in FVIII levels in the moderate to normal range, without sustained AEs and with minimal overall bleeding in the highest-dose cohort (3e13 vg/kg). The ongoing phase 3 study (NCT04370054) in a larger cohort will provide more long-term data to further characterize the safety and durability of giroctocogene fitelparvovec in patients with moderately severe to severe hemophilia A."

Clinical • P1/2 data • Cardiovascular • Gastrointestinal Cancer • Gene Therapies • Hematological Disorders • Hemophilia • Hepatocellular Cancer • Hypotension • Liver Cancer • Rare Diseases • Solid Tumor

Updated Results of the Alta Study, a Phase 1/2 Study of Giroctocogene Fitelparvovec (PF-07055480/SB-525) Gene Therapy in Adults with Severe Hemophilia a (ASH 2021) - P2, P3 | "A single infusion of giroctocogene fitelparvovec gene therapy in patients with severe hemophilia A was generally well tolerated with associated increases in FVIII levels in the mild to normal range, without sustained AEs, and with minimal bleeding in the highest-dose cohort (3e13 vg/kg). A phase 3 study (NCT04370054) of giroctocogene fitelparvovec in patients with hemophilia A is ongoing."

Clinical • P1/2 data • Cardiovascular • Gene Therapies • Hematological Disorders • Hemophilia • Hypotension • Rare Diseases

NAB PROTOCOL: A Study to Evaluate Prospective Efficacy and Safety Data of Current FIX Prophylaxis Replacement Therapy in Adult Hemophilia B Subjects (FIX:C≤2%) or Current FVIII Prophylaxis Replacement Therapy in Adult Hemophilia A Subjects (FVIII:C≤1%) (clinicaltrials.gov) - P3 | N=250 | Recruiting | Sponsor: Pfizer | Trial completion date: May 2023 ➔ Sep 2023 | Trial primary completion date: May 2023 ➔ Sep 2023

Trial completion date • Trial primary completion date • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

AFFINE: Study to Evaluate the Efficacy and Safety of PF-07055480 / Giroctocogene Fitelparvovec Gene Therapy in Moderately Severe to Severe Hemophilia A Adults (clinicaltrials.gov) - P3 | N=63 | Recruiting | Sponsor: Pfizer | Active, not recruiting ➔ Recruiting | Trial completion date: Sep 2027 ➔ Mar 2028 | Trial primary completion date: Sep 2023 ➔ Mar 2024

Enrollment open • Trial completion date • Trial primary completion date • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases • CD4

NAB PROTOCOL: Six Month lead-in Study to Evaluate Prospective Efficacy and Safety Data of Current FIX Prophylaxis Replacement Therapy in Adult Hemophilia B Subjects (FIX:C≤2%) or Current FVIII Prophylaxis Replacement Therapy in Adult Hemophilia A Subjects (FVIII:C≤1%) (clinicaltrials.gov) - P3 | N=250 | Recruiting | Sponsor: Pfizer | Active, not recruiting ➔ Recruiting | N=169 ➔ 250 | Trial completion date: Jan 2023 ➔ May 2023 | Trial primary completion date: Jan 2023 ➔ May 2023

Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Sangamo Therapeutics Reports Fourth Quarter and Full Year 2021 Financial Results and Recent Business Highlights (Businesswire) - "Sangamo Therapeutics, Inc...today reported fourth quarter and full year 2021 financial results and recent business highlights....Revenues were $110.7 million in 2021, compared to $118.2 million in 2020. The decrease in revenues was primarily due to a decrease of $47.4 million of milestone fees and recognition of upfront license fees related to our giroctocogene fitelparvovec..."

Commercial • Gene Therapies • Genetic Disorders • Hemophilia

NAB PROTOCOL: Six Month lead-in Study to Evaluate Prospective Efficacy and Safety Data of Current FIX Prophylaxis Replacement Therapy in Adult Hemophilia B Subjects (FIX:C≤2%) or Current FVIII Prophylaxis Replacement Therapy in Adult Hemophilia A Subjects (FVIII:C≤1%) (clinicaltrials.gov) - P3 | N=169 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | N=250 ➔ 169 | Trial completion date: Oct 2022 ➔ Jan 2023 | Trial primary completion date: Oct 2022 ➔ Jan 2023

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Pfizer Reports Fourth-Quarter and Full-Year 2021 Results (Businesswire) - "Pfizer Inc...reported strong financial results for fourth-quarter and full-year 2021 and provided 2022 total company financial guidance...Paxlovid, which contributed $76 million in U.S. sales after the U.S. Food and Drug Administration (FDA) authorized the treatment for emergency use in late-December 2021; Xeljanz, up 4% operationally, driven primarily by favorable wholesaler inventory buying patterns in the U.S., as well as growth in the emerging markets from the rheumatoid arthritis indication....A total of 2.75 million courses are expected to be delivered to the U.K. through 2022....The Phase 3 AFFINE clinical trial of giroctocogene fitelparvovec in patients with hemophilia A has started and is over 50% enrolled. Following the observation of FVIII levels greater than 150% in some treated patients, Pfizer voluntarily paused screening...Pfizer hopes to obtain agreements to proceed and begin to reopen trial sites in the first half of 2022."

Commercial • Enrollment status • Sales • Trial status • Ankylosing Spondylitis • Genetic Disorders • Hemophilia • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Novel Coronavirus Disease • Psoriatic Arthritis • Rheumatoid Arthritis • Ulcerative Colitis

AFFINE: Study to Evaluate the Efficacy and Safety of PF-07055480 / Giroctocogene Fitelparvovec Gene Therapy in Moderately Severe to Severe Hemophilia A Adults (clinicaltrials.gov) - P3 | N=63 | Active, not recruiting | Sponsor: Pfizer | Trial completion date: Jan 2027 ➔ Sep 2027 | Trial primary completion date: Jan 2023 ➔ Sep 2023

Trial completion date • Trial primary completion date • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases • CD4

Pfizer and Sangamo Announce Updated Phase 1/2 Results Showing Sustained Bleeding Control in Highest Dose Cohort Through Two Years Following Hemophilia A Gene Therapy (Businesswire) - P2, N=11; Alta study (NCT03061201); Sponsor: Pfizer; "Pfizer Inc...and Sangamo Therapeutics, Inc...today announced updated follow-up data from the Phase 1/2 Alta study of giroctocogene fitelparvovec....The Alta study data, in patients with severe hemophilia A, are being presented today at the 63rd American Society for Hematology Annual Meeting and Exposition taking place from December 11-14 virtually and in Atlanta, GA....At 104 weeks, the five patients in the highest dose 3e13 vg/kg cohort had mean factor VIII (FVIII) activity of 25.4%...mean annualized bleeding rate (ABR) was 0.0 in the first year post-infusion and was 1.4 throughout the total duration of follow-up as of the October 1, 2021 cutoff date. All bleeding events occurred after week 69 post-infusion. Two patients experienced bleeding events necessitating treatment with exogenous FVIII..."

P1/2 data • Genetic Disorders • Hemophilia

Phase 3 Trial of Gene Therapy SB-525 for Hemophilia A on FDA Hold (Hemophilia News Today) - "The U.S. Food and Drug Administration (FDA) has placed a clinical hold on the Phase 3 trial evaluating SB-525 (giroctocogene fitelparvovec), an investigational gene therapy for hemophilia A. This pause in study recruitment and dosing was taken to give the agency time to review changes to the AFFINE trial’s protocol after unusually high factor levels were reported in some treated patients...After being treated, some patients showed FVIII levels greater than 150%, and higher-than-usual factor levels raise a risk of blood clots."

Trial suspension • Genetic Disorders • Hemophilia

Pfizer (PFE) Q3 2021 Earnings Call Transcript (The Motley Fool) - "...In hemophilia A, we have temporarily and voluntarily paused screening and dosing in our Phase 3 study evaluating Factor 8 gene therapy...in order to implement the protocol amendment following the observance of Factor 8 levels greater than 150% in some trial participants....We are committed to resuming dosing as quickly as possible once a protocol amendment, which is intended to provide guidelines for clinical management of elevated Factor 8 levels is implemented. Separately, based on recent interaction with the FDA, Pfizer no longer plans to conduct an interim analysis of Phase 3 data from our hem A and B gene therapy programs. We anticipate pivotal data readouts to be based on full analysis of at least 50 study participants for hem A and 40 participants for the hemophilia B program. This will push out the timing of readouts of those trials compared to our previous expectations....For hemophilia B, we anticipate the readout in the first quarter of '23."

P3 data • Trial suspension • Gene Therapies • Genetic Disorders • Hemophilia