Sangamo Announces Interim Results Of Phase 1/2 EMPOWERS Study Evaluating SB-318 Zinc Finger Nuclease (ZFN) In Vivo Genome Editing Demonstrating Increased Leukocyte IDUA Activity In Patients With MPS I
"The results so far suggest a dose-dependent increase in leukocyte IDUA enzyme activity," said Dr.
MPS I, also known as Hurler syndrome, is a rare genetic disorder caused by a deficiency of alpha-L-iduronidase (IDUA), a lysosomal enzyme which is required to break down or recycle the toxic buildup of glycosaminoglycans (GAGs). Without IDUA enzyme activity, GAGs accumulate in cells throughout the body, leading to widespread tissue and organ damage. The current standard-of-care treatment for MPS I is enzyme replacement therapy (ERT), given as weekly intravenous infusions. For severe MPS I patients, bone marrow transplant is also a common treatment. SB-318 is an investigational product candidate being evaluated to treat MPS I using ZFNs, which are designed to insert a normal copy of the IDUA gene into a precise location in the DNA of liver cells. The goal of SB-318 treatment is to enable a patient's liver to produce a continuous supply of functional IDUA enzyme.
"It is a tremendous responsibility to undertake the first in vivo genome editing clinical trials, and we are learning quickly about our technology and about these rare diseases," said Dr.
Interim EMPOWERS Study Results Presented at WORLDSymposium
The primary objective of the EMPOWERS Study is to determine the safety and tolerability of SB-318, and secondary objectives include evaluation of change from baseline in IDUA activity and urine GAG levels. Biochemical measurements of urinary GAGs, as well as plasma and leukocyte IDUA activity, are assessed at screening and baseline visits, and every two to four weeks during the initial phase of the trial.
Patients with mild MPS I receiving weekly ERT were enrolled in the study. One patient has been dosed with 1e13 vector genomes per kilogram body weight (vg/kg) of SB-318 and two patients have been dosed with 5e13 vg/kg of SB-318. None of the three patients enrolled in the study have received a bone marrow transplant.
Safety data were collected and analyzed for the three patients.
The results suggest a dose-dependent increase in leukocyte IDUA activity, with activity levels rising above baseline and in the normal range (normal range is 6.0-71.4 nmol/hr/mg). Plasma IDUA activity was unchanged from baseline in all three patients.
Baseline urine GAG measurements for the three patients in the EMPOWERS Study were in a range considered to be at or slightly above normal. In the limited duration data set available at the time of the WORLDSymposium presentation, urine GAG measurements show no meaningful change.
The clinical relevance of the biochemical changes observed following administration of SB-318 will be assessed as clinical data and patient outcomes are analyzed following a trial of withdrawal from ERT. ERT withdrawal is expected for these patients later in 2019. Sangamo also expects to report analyses of liver biopsies later this year.
Sangamo has developed second-generation, potentially more potent ZFN constructs designed to increase editing efficiency. Preclinical data of these second-generation ZFNs were reviewed by U.S. regulators. The preclinical data showed three potential advantages for use in the clinic: (1) a 5- to 30-fold improvement in efficiency and potency due to structural changes; (2) the ability to function equally well in the patients who have a single nucleotide polymorphism (SNP) in the target locus in the albumin gene (approximately 20% of the population); (3) improved specificity. The second-generation ZFNs are already being manufactured and are expected to be ready for use in the clinic later this year. Additional data from Sangamo's in vivo genome editing programs will be assessed before potential integration plans for the second-generation ZFNs are finalized.
Sangamo will host a conference call today,
The conference call dial-in numbers are (877) 377-7553 for domestic callers and (678) 894-3968 for international callers. The conference ID number for the call is 4387585. For those unable to listen in at the designated time, a conference call replay will be available for one week following the call. The conference call replay numbers for domestic and international callers are (855) 859-2056 and (404) 537-3406, respectively. The conference ID number for the replay is 4387585.
This press release contains forward-looking statements based on Sangamo's current expectations. These forward-looking statements include, without limitation, statements relating to the potential therapeutic applications for SB-318 and SB-913, the potential for SB-318 to treat MPS I, including the potential for increased leukocyte IDUA activity to translate into clinical benefit and for SB-318 to potentially cause the liver to produce a continuous supply of functional IDUA enzyme, the timing and nature of additional data from SB-318, the potential advantages of second-generation ZFNs, the timing of the use of the second-generation ZFNs, Sangamo's belief that the second-generation ZFNs have the potential for greater benefit for patients, and other statements that are not historical fact. These statements are not guarantees of future performance and are subject to certain risks, uncertainties and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties related to early data, including the risk that the early data from the EMPOWERS Study may not be representative of final results after all patients are treated in the study and all data are collected and analyzed; Sangamo's ability to complete the EMPOWERS Study and the CHAMPIONS Study; whether the final results from the EMPOWERS Study and CHAMPIONS Study will validate and support interim results and the overall safety and efficacy of SB-318 and SB-913, respectively, including the risk that the early efficacy data from the EMPOWERS Study and the CHAMPIONS Study may not be maintained or replicated; whether Sangamo will be able to effectively deliver its ZFNs to produce a beneficial therapeutic effect, including the risks that the second-generation ZFNs may not be successfully integrated into Sangamo's product candidates and even if successfully integrated, the second-generation ZFNs may not have any advantages over Sangamo's first-generation ZFNs or otherwise may not produce any beneficial therapeutic effect; Sangamo's reliance on partners and other third-parties to meet their clinical and manufacturing obligations, and its ability to maintain strategic partnerships. Further, there can be no assurance that the necessary regulatory approvals for SB-318 or SB-913 will be obtained or that Sangamo and its partners will be able to develop commercially viable product candidates for the treatment of MPS I, MPS II and other diseases. These risks and uncertainties are described more fully in Sangamo's Quarterly Report on Form 10-Q for the quarter ended
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