US regulators approve two gene therapies for sickle cell disease
The US Food and Drug Administration has approved a pair of gene therapies for sickle cell disease, including the first treatment based on the breakthrough Crispr gene-editing technology, opening up two “transformative therapy” avenues for some patients.
The FDA approved Lyfgenia from Bluebird Bio, and a separate treatment called Casgevy by partners Vertex Pharmaceuticals and Crispr Therapeutics. Both therapies are made from the patients’ own blood stem cells and were approved for people aged 12 and older.
The Vertex/Crispr gene therapy uses the breakthrough gene-editing technology that won its inventors the Nobel prize in 2020. The therapy can be directed to cut DNA in targeted areas, enabling the ability to accurately remove, add or replace DNA where it was cut.
The modified blood stem cells are then transplanted back into the patient, where they attach and multiply within the bone marrow and increase the production of fetal hemoglobin, a type of hemoglobin that facilitates oxygen delivery.
Lyfgenia is a cell-based gene therapy that modifies a patient’s blood stem cells to produce a gene therapy-derived hemoglobin that functions similarly to a type of normal adult hemoglobin not affected by sickle cell disease.
Sickle cell disease is a painful, inherited blood disorder that can be debilitating and lead to premature death. It affects an estimated 100,000 people in the US, is most common in African Americans and, while less prevalent, also affects Hispanic Americans.
President Biden said in a statement that the approval of the treatments represented a “major breakthrough” for those living with the disease and noted that it disproportionally affected the two minority groups.
“My administration has worked tirelessly to close these health disparities and help deliver care for sickle cell disease patients and their families, and we will continue to do so,” he said, adding that his administration would continue “efforts to accelerate the development of cures for rare diseases and support the medical research and innovation”.
In sickle cell disease, the body makes flawed, sickle-shaped hemoglobin, impairing the ability of red blood cells to properly carry oxygen to the body’s tissues. The sickle cells tend to stick together and can block small blood vessels, causing intense pain. It also can lead to strokes and organ failure.
“Sickle cell disease is a rare, debilitating and life-threatening blood disorder with significant unmet need, and we are excited to advance the field especially for individuals whose lives have been severely disrupted by the disease by approving two cell-based gene therapies today,” said Nicole Verdun, director of the office of therapeutic products within the FDA’s Center for Biologics Evaluation and Research, said in a statement.
“Gene therapy holds the promise of delivering more targeted and effective treatments, especially for individuals with rare diseases where the current treatment options are limited,” Verdun added.
Makers of both the therapies have pitched them as one-time treatments, but data on how long their effect lasts is limited. The only longer-term treatment for sickle cell disease is a bone marrow transplant.
“I actually am very reticent to call them a cure. I prefer to call them a transformative therapy because patients will still have sickle cell disease on the other side of gene therapy,” said Sharl Azar, medical director of the Comprehensive Sickle Cell Disease Treatment Center at Massachusetts general hospital.
Both gene therapies can take several months and involve high-dose chemotherapy, but this has potential risks of infertility.
“Not everybody who undergoes chemotherapy will end up having infertility, but the majority of them will,” said Azar.
While the risk can be managed by fertility preservation methods such as freezing eggs and sperm banking, this is only covered by insurance for cancer patients who undergo chemotherapy and not those receiving gene therapy, said Azar.
He said the out-of-pocket expense on it can be as high as $40,000.
FDA staff in documents released ahead of an October meeting of a panel of independent experts on Vertex’s therapy had also flagged concerns of unintended genomic alterations from the treatment.
The company plans to assess potential long-term safety risks through a 15year follow-up study after approval.
Reuters contributed to this report
protections for one use case inevitably leads governments and other bad actors to use those entry points for surveillance and other nefarious purposes, they argue.
“This level of security not only protects individuals from cyber-attacks but also empowers citizens to communicate freely without fear of surveillance, censorship, and warrantless searches – whether by the government, Big Tech, data brokers, or anyone else,” read an October statement from the American Civil Liberties Union, a nonprofit human rights organization.
Meta said in a statement to NBC: “We don’t think people want us reading their private messages so we have spent the last five years developing robust safety measures to prevent and combat abuse while maintaining online security. We continue to strengthen our enforcement systems to root out potentially predatory accounts.”
Messenger is no stranger to content depicting the abuse of children. A Guardian investigation in April revealed how Meta is failing to report or detect the use of its platforms for child trafficking and uncovered how Messenger is being used as a platform for traffickers to communicate to buy and sell children. In 2018, a video of an adult man sexually abusing an underage girl spread to thousands of people via Messenger under the guise of outrage over what the video showed.
Encryption will create barriers to collecting evidence and prosecuting criminals who want to target children over Meta platforms, child sex trafficking experts said.
“It is a dereliction of their ethical and moral duty of care to society to knowingly bring about changes to their platform, knowing full well that the net effect will be to mask and provide plausible deniability over a problem they have failed to contain over the years,” said Lianna McDonald, executive director of the Canadian Centre for Child Protection, a non-profit. “Regulation cannot come soon enough.”
Kristina Korobov, senior attorney for the non-profit Zero Abuse Project and former assistant US attorney in Indiana, called encryption “a real threat to kids”. She said the dangers of Facebook hide behind a veil: “It’s often viewed as ‘safe’ by parents for use by teens.”
In one of Burns’s recent cases in Illinois, an American man named Joseph Fuchs was sentenced to 126 months of jail in December 2022 for grooming a 14-year-old child in the Philippines and traveling there to engage in illicit sex with her.
Fuchs, 52, had located the girl on Facebook and groomed her over Facebook Messenger. Illinois law enforcement was alerted to Fuchs’s crimes by a report that Meta made to NCMEC. Transcripts from Fuchs’s trial show some of the communications between Fuchs and the child took place over Facebook Messenger, which investigators say they were able to obtain because the communications were not encrypted.
“In this case, we wouldn’t have ever known about it if Facebook had not flagged it,” said Burns.
• In the US, call or text the Childhelp abuse hotline on 800-422-4453 or visit their website for more resources and to report child abuse or DM for help. For adult survivors of child abuse, help is available at ascasupport.org. In the UK, the NSPCC offers support to children on 0800 1111, and adults concerned about a child on 0808 800 5000. The National Association for People Abused in Childhood (Napac) offers support for adult survivors on 0808 801 0331. In Australia, children, young adults, parents and teachers can contact the Kids Helpline on 1800 55 1800, or Bravehearts on 1800 272 831, and adult survivors can contact Blue Knot Foundation on 1300 657 380. Other sources of help can be found at Child Helplines International