FDA Approves First Gene Therapy for Severe Hemophilia A
The FDA has approved Roctavian (valoctocogene roxaparvovec-rvox), a gene therapy developed by BioMarin Pharmaceutical, for the treatment of severe hemophilia A in adult males. This marks a notable advancement in the treatment of this inherited bleeding disorder, offering the potential for a one-time, long-term solution.
Hemophilia A is caused by a deficiency in clotting factor VIII, leading to prolonged bleeding after injury, surgery, or even spontaneously. Current treatment typically involves lifelong prophylactic infusions of factor VIII to prevent bleeding episodes.
Roctavian utilizes an adeno-associated virus (AAV) vector to deliver a functional copy of the factor VIII gene to liver cells. This allows the body to produce its own factor VIII, potentially reducing or eliminating the need for regular infusions.
The approval is based on data from a clinical trial demonstrating sustained increases in factor VIII activity and a significant reduction in annualized bleeding rates in participants. While not a cure, Roctavian offers the possibility of a dramatically improved quality of life for individuals with severe hemophilia A.
The therapy carries a boxed warning regarding the potential for liver-related adverse events and immune responses. Patients will require long-term monitoring of liver function and factor VIII activity.
Roctavian is expected to be available through a limited number of specialized treatment centers with experience in gene therapy. The cost of the therapy is significant, reflecting the complexity of its development and manufacturing.## Donor-Derived Tuberculosis: A Rare but serious Risk in Organ Transplantation
“Donor-derived TB is a rare but serious complication of solid organ transplantation, particularly in the United States,” Paulina Vega, MD, an infectious disease fellow at the University of washington, told Healio. “Given how infrequently donor-derived TB is reported and the diagnostic challenges it presents, we felt it was important to contribute to the literature and raise awareness among clinicians.”
In their paper, Vega and colleagues described three cases of donor-derived TB among patients who had received the kidneys and liver of the same deceased donor.
The donor had an unknown medical history but was born in a TB-endemic area, according to the authors. The donor was not screened for TB but did undergo CT scans of the chest that showed bilateral consolidations and multinodular opacities, which were interpreted as aspiration pneumonia, according to Vega and colleagues. Respiratory cultures identified Klebsiella pneumoniae.
After pre-transplant testing, one of the donor’s kidneys was transplanted to a woman in her 50s who had undergone TB treatment 2 years before transplantation. The other kidney was transplanted to a man in his 70s with no history of TB, and the donor’s liver was given to another man in his 70s with no history of TB.
Within six weeks,all three patients had sought care for unexplained fevers,among other symptoms.
According to the report, after initial antibacterial therapy was unsuccessful for all three patients, additional testing turned up positive for mycobacterium tuberculosis.
The woman who received one of the kidneys had surgery to remove the transplanted organ six weeks later due to TB infection but ultimately recovered. The other two patients experienced prolonged hospitalizations but also recovered following TB treatment and kept their respective organs.”Although donor-derived TB is uncommon, our findings show that when it does occur, it can lead to significant morbidity, including prolonged hospitalization and treatment-related complications,” vega said.
She added that more thorough screening would be ideal; though, implementing universal TB screening in deceased donors “must be balanced against feasibility, cost, organ availability and the risk of unnecessary organ discard.”
Vega explained that while living donors are routinely screened for TB, screening deceased donors is “much more challenging.” Some of the challenges with screening deceased donors include the limited sensitivity.