According to corporate news shared on Street Insider, biopharmaceutical company BridgeBio Pharma, Inc. (“BridgeBio”) is making ground with its AAV5 gene therapy, BBP-631. Recently, the FDA granted Fast Track designation to BBP-631, which was developed to treat patients with congenital adrenal hyperplasia (CAH).
So what is BBP-631? According to BridgeBio, the therapy is:
an investigational adeno-associated virus (AAV) gene therapy to treat CAH due to 21-hydroxylase deficiency at its source. BBP-631 is designed to deliver a functional copy of the 21-hydroxylase gene and…if successful, we hope to restore the body’s ability to both make and regulate hormone production, producing the right amount of hormone at the right time.
Altogether, BridgeBio developed BBP-631 to offer new and improved care to patients with CAH. Currently, the standard-of-care (SOC) has remained relatively stable over the past five decades. Thus, BBP-631 would offer patients the ability to produce cortisol and aldosterone, allowing for more efficient and less invasive treatments.
The Fast Track designation allows for expedited development and review. In particular, Fast Track designation is granted to drugs or biologics designed to either treat serious conditions or fill an unmet medical need. Serious conditions are those which impact survival or daily functioning. Beyond Fast Track designation, BBP-631 also received Orphan Drug and Rare Pediatric Disease designations in the United States, as well as Orphan Drug designation within the European Union (EU).
Preclinical Data on BBP-631
Some of the preclinical data on BBP-631 highlights the therapy’s potential benefits. The data was shared at the American Society of Gene & Cell Therapy (ASGCT) virtual annual meeting. In one presentation, Dr. Rachel Eclov, PhD, discussed how intravenously administered gene therapy helped fix phenotypic issues in mice models of CAH. Overall, the data highlighted safety, efficacy, and tolerability. In an upcoming Phase 1/2 clinical trial, researchers hope to see similarly beneficial outcomes in human patients.
Congenital Adrenal Hyperplasia (CAH)
In nearly 95% of congenital adrenal hyperplasia (CAH) diagnoses, the inherited genetic disorder is caused by enzyme 21-hydroxylase deficiencies. Because CAH is inherited in an autosomal recessive pattern, patients must receive one defective gene from each parent in order to develop this condition. CAH affects the adrenal glands, or walnut-sized organs above the kidneys. Normally, the adrenal glands play a role in metabolism and immune system regulation, blood pressure regulation, and hormone secretion. But when patients lack 21-hydroxylase, this prevents the immune system from working properly. As a result, hormone production is thrown out of whack.
There are two main forms of CAH: classic and nonclassic. Typically, the classic form is severe with an onset in infancy. Symptoms include:
- Severe cortisol shortage
- Difficulty managing blood pressure or blood sugar
- Inability to maintain adequate sodium levels in the body
- Abnormal genital development
- Excess testosterone
- Short height/stature
- Frequent vomiting
- Unintended weight loss
- Early puberty
In nonclassic CAH, symptoms are typically milder and may not appear until childhood or early adulthood. These symptoms include:
- Severe acne
- Irregular or absent menstruation
- Early armpit or pubic hair growth
- Rapid childhood growth, culminating in a shorter than average height