Rocket Pharmaceuticals ( NASDAQ: RCKT ) said its gene therapy RP-A501 was safe, well tolerated and showed clinical benefit in two children and four adults in a phase 1 trial to treat Danon Disease (DD).
DD is a rare genetic condition characterized by weakening of the heart muscle, skeletal muscles and intellectual disability. It is a type of a lysosomal storage disorder in which the defect is caused by variations in the LAMP2 gene.
RP-A501, which is being developed for Danon Disease and the first potential gene therapy for monogenic heart failure, consists of a recombinant adeno-associated serotype 9 (AAV9) capsid containing a functional version of the human LAMP2B transgene (AAV9.LAMP2B), the the company said in a Sept. 30 press release.
The phase 1 trial evaluated a single intravenous infusion of RP-A501.
The company said early pediatric efficacy data were consistent with initial improvements seen in adult patients at a similar timeframe of up to nine months follow-up and sustained clinical benefit across biomarker, clinical and functional parameters in currently enrolled adult patients at 24 to 36 months of follow-up.
In the pediatric group, LAMP2B gene expression by immunohistochemistry was 21.1% in the first patient (1008) at six months and 34.7% in the second patient (1009) at three months.
"Results showed RP-A501 was generally well tolerated with evidence of durable treatment effect and improvement of Danon Disease, including for both pediatric patients with up to nine months of follow-up and four adult patients with up to 36 months of follow-up," said Rocket CEO Gaurav Shah.
Rocket added that vacuolar area was decreased by 77% at six months in the first patient. In addition, Brain natriuretic peptide (BNP) a marker of heart failure, decreased from a pretreatment baseline by 78% in the first pediatric patient at nine months and by 62% in the second child at six months.
All patients in the pediatric and adult groups showed stabilization or meaningful decreases in BNP.
The company noted that in children, despite a limited six and nine months of follow-up, decreases in high sensitivity troponin I (hsTnI) — a protein, high levels of which indicate heart damage — of 90% and 85%, respectively were seen.
In the four adult patients a reduction in troponin of >75% from mean pretreatment baseline was seen to average values at 18 to 24 months which was sustained in three adults who are currently 30 to 36 months post-treatment, according to the company.
In addition, an improvement (from Class 2 to 1) in New York Heart Association (NYHA) class, a measure of symptoms/functional limitations due to heart failure, was seen in both children.
Rocket added that RP-A501 was seen to be generally well tolerated at the low dose with a manageable safety profile across pediatric and adult groups.
The two children received a modified immunomodulatory regimen to mitigate adverse events, the company noted.
Rocket said the data to date is expected to support a phase 2 study in in DD.
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Rocket's gene therapy for heart disease shows promise in children/adults in phase 1 trial