The risk of unintentional cancer caused by gene therapy has enveloped this emerging field. As BioMarin Pharmaceutical revealed safety signals in animal research, the FDA placed it on Clinical reservation In a trial evaluating the company’s experimental treatment for rare enzyme deficiencies.
To date, no cancer has been reported in humans or large animals taking BMN 307 (BioMarin’s experimental gene therapy for phenylketonuria (PKU)). But with the implementation of clinical trials, no new patients will participate in this study.
The cancer risk of gene therapy comes from the engineered virus used to deliver the therapeutic gene payload into the cell. If the virus inserts its DNA into the patient’s genome, the integration may cause cancer. This phenomenon is called integrative tumorigenesis.
Phenylketonuria is a genetic defect of phenylalanine hydroxylase (PAH). Phenylalanine hydroxylase (PAH) is an enzyme required to break down phenylalanine. Phenylalanine is found in certain foods. An amino acid found in. Without this enzyme, amino acid levels can reach dangerous levels. This situation is mainly controlled by avoiding certain foods. San Rafael, California-based BioMarin introduced BMN 307 to the clinic last year. Previously reported mouse research data showed that the therapy resulted in lifelong normalization of phenylalanine.
The cancer risk announced by BioMarin during the Labor Day holiday comes from the company’s ongoing mouse research to evaluate the durability of its gene therapy. The research is conducting gene therapy on mice with two genetic mutations that may make them susceptible to cancer. BioMarin said that in the 63 mice administered in the study, no abnormal cells were observed after 24 weeks. But after 52 weeks, tests showed that of the 7 mice given the highest dose, 6 had liver tumors.
BioMarin said that preliminary results also show that there is evidence that part of the adeno-associated virus used to provide gene therapy has been integrated into the mouse genome. Five of the mice had adenoma, a non-cancerous tumor, and one had liver cancer. The company added that it is still investigating how or whether these findings apply to humans.
The cancer problem has brought other gene therapy programs to a standstill.At the end of last year, the FDA issued a Clinical reservation After a patient in the study developed liver cancer, he received uniQure hemophilia B gene therapy. April, the FDA approves Dutch company to resume the study After independent investigation found There is no evidence that the patient’s cancer was caused by experimental gene therapy.
The Phase 1/2 clinical trial of BMN 307 is an open-label, dose-escalation study aimed at enrolling 100 patients. Earlier this year, the company announced plans to increase the dose in the study based on encouraging data that showed reduced levels and safety of phenylalanine were observed in participants receiving the lowest dose of treatment. According to the company, none of the patients in the clinical trials received the same high doses as mice that developed liver tumors.
The BioMarin clinical trial was discussed at a meeting of the FDA last week Safety risks of gene therapyIn a prepared statement, Hank Fuchs, BioMarin’s global president of R&D, acknowledged the discussion at the meeting regarding the risks of integration mutations observed in mice using other viral vectors, and promised to investigate his company’s gene therapy findings.
“For patients who have received lower doses of these carriers, we will continue to carefully evaluate and monitor their health,” Fuchs said. “We are committed to understanding and reducing any risk of cancer.”
BioMarin already has two PKU products: Kuvan, which is taken orally and must be accompanied by diet management; Palynziq, which is injected once a day with a black box warning to remind doctors and patients of the risk of allergic reactions. With BMN 307, BioMarin aims to provide an alternative and possibly better way to normalize phenylalanine levels in the blood without strict dietary restrictions.
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