Sangamo & Pfizer Update Results for their SB-525 Investigational Hemophilia A Gene Therapy Revealing Sustained Increased Factor VIII Levels

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Sangamo Therapeutics and Pfizer announced updated results from the Phase 1/2 Alta Study evaluating investigational SB-525 gene therapy for severe hemophilia A. The data reveals that SB-525 was generally well tolerated and demonstrated a dose-dependent increase in Factor VIII activity levels.

TrialSite News breaks down the updates to this important study.

What is the Alta Study?

The Phase 1/2 Alta study is an open-label, dose-ranging clinical trial designed to assess the safety and tolerability of SB-525 in patients with severe hemophilia A. The mean age of the ten patients assessed is 31 years (range 18-47). All ten patient is male. The US FDA has granted Orphan Drug, Fast Track, and regenerative medicine advanced therapy (RMAT) designation to SB-525, which also received Orphan Medicinal Product designation from the European Medicines Agency. SB-525 is being developed as part of a global collaboration between Sangamo and Pfizer.

Summary of Potential Update

  •         Hemophilia A patients taking the highest dose of this essential gene therapy are exhibiting significant boosts in levels of an important blood-clotting protein, offering Sangamo the opportunity to compete for leading efficacy against a competitive grouping in the market.
  •         With this new interim data presented at an Australian conference, it reveals patients who received the highest dose of SB-525 are sustaining normal levels of the essential protein that hemophilia patients lack—Factor VIII
  •         These results are from a Phase 1/2 study. BioMarin and Spark Therapeutics have investigational gene therapy hemophilia treatments further advanced down the pipeline—in Phase 3. However SB-525 results reveal it could be competitive with these other treatments.

The Results Thus Far

The data has shown thus far that SB-525 has been generally well-tolerated and demonstrated a dose-dependent increase in Factor VIII (FVIII) activity levels. The first two patients treated at the 3e13 vg/kg dose rapidly achieved normal levels of FVIII activity as measured using a chromogenic assay, with no reported bleeding events, and the response continues to be durable for as long as 24 weeks, the extent of the follow-up. The two patients more recently treated at the 3e13 vg/kg dose level are demonstrating FVIII activity kinetics that appears consistent with the first two patients treated in this dose cohort at similar early time points. The data from 10 patients treated with SB-525 were presented during an oral presentation on July 6 at the XXVII Congress of the International Society of Thrombosis and Haemostasis (ISTH) in Melbourne, Australia.

The Alta study data presented at ISTH included 10 patients treated across four ascending dose cohorts: 9e11 vg/kg (2 patients), 2e12 vg/kg (2 patients), 1e13 vg/kg (2 patients) and 3e13 vg/kg (4 patients). Factor VIII activity presented at ISTH included results through June 18, 2019. All other data presented at ISTH were as of May 30, 2019.

Investigator Comments

Barbara Konkle, MD, Bloodworks Northwest, Professor of Medicine at University of Washington and Principal Investigator of the Alta Study noted “It is encouraging that patients in the 3e13 vg/kg cohort have attained normal Factor VIII levels within 5-7 weeks of treatment with SB-525 gene therapy and have sustained Factor VIII levels with no bleeding episodes. It will be important to continue to follow these patients to understand the potential long term durability of this gene therapy.”

What is Sangamo’s SB-525 Gene Therapy?

SB-525 comprises a recombinant adeno-associated virus serotype 6 vector (AAV6) encoding the complementary deoxyribonucleic acid for B domain deleted human FVIII. The SB-525 vector cassette was designed to optimize both the vector manufacturing yield and liver-specific FVIII liver-specific FVIII protein expression. The SB-525 transcriptional cassette incorporates multi-factorial modifications to the liver-specific promoter module, FVIII transgene, synthetic polyadenylation signal, and vector backbone sequence.

How does SB-525 Work?

We reviewed Hemophilia News Today for more information on SB-525. The goal is to reduce or eliminate the need for coagulation factor VIII replacement therapy by getting cells to naturally produce this important protein.

Composed of a small portion of genetic material with the code for the production of factor VIII, once inside the cells, SB-525 binds to the existing genetic material to allow for the correct formation of this coagulation factor through the normal processes of cellular protein formation.

SB-525 has genetic information within carried and delivered to liver cells (where coagulation factors are produced) using a modified, harmless form of the adeno-associated virus, which normally travels to the liver and infects the organ. A single SB-525 administration may provide a durable production of coagulation factor VIII in liver cells, which is then carried into the bloodstream and can assist in the formation of blood clots, protecting against bleeding complications in hemophilia patients.

About Sangamo Therapeutics

A biotech venture focusing on translating ground-breaking science into genomic medicines with the potential to transform a patient’s lives. Their capabilities in gene therapy, cell therapy, genome editing, and gene regulation enable them to apply the appropriate therapeutic approach to the underlying genetic cause of the disease.