After Casgevy Follows A Genome Editing Bevy

Today, December 8, 2023, the United States Food and Drug Administration ("FDA") emulated its British equivalent, the Medicines and Healthcare products Regulatory Agency, by approving the CRISPR/Cas9-based therapy Casgevy, a gene editing treatment for sickle cell disease ("SCD").  As it did in the United Kingdom, this approval marks a milestone in therapeutic history in the United States.   Here is how the FDA described Casgevy:

Casgevy, a cell-based gene therapy, is approved for the treatment of sickle cell disease in patients 12 years of age and older with recurrent vaso-occlusive crises. Casgevy is the first FDA-approved therapy utilizing CRISPR/Cas9, a type of genome editing technology. Patients’ hematopoietic (blood) stem cells are modified by genome editing using CRISPR/Cas9 technology.

CRISPR/Cas9 can be directed to cut DNA in targeted areas, enabling the ability to accurately edit (remove, add, or replace) DNA where it was cut. The modified blood stem cells are transplanted back into the patient where they engraft (attach and multiply) within the bone marrow and increase the production of fetal hemoglobin (HbF), a type of hemoglobin that facilitates oxygen delivery. In patients with sickle cell disease, increased levels of HbF prevent the sickling of red blood cells.

The FDA was impressed by the strong performance of Casgevy in clinical trials:

The safety and effectiveness of Casgevy were evaluated in an ongoing single-arm, multi-center trial in adult and adolescent patients with SCD. Patients had a history of at least two protocol-defined severe VOCs during each of the two years prior to screening. The primary efficacy outcome was freedom from severe VOC episodes for at least 12 consecutive months during the 24-month follow-up period. A total of 44 patients were treated with Casgevy. Of the 31 patients with sufficient follow-up time to be evaluable, 29 (93.5%) achieved this outcome. All treated patients achieved successful engraftment with no patients experiencing graft failure or graft rejection. 

The most common side effects were low levels of platelets and white blood cells, mouth sores, nausea, musculoskeletal pain, abdominal pain, vomiting, febrile neutropenia (fever and low white blood cell count), headache and itching.

The FDA granted the license for Casgevy to biotechnology firm, Vertex Pharmaceuticals Inc..  However, many other biotechnology and pharmaceutical companies are waiting in the line for the FDA to grant approval to their genome editing therapies. 

Clonan the Barbarian and the Mastiff Landslide

 Argentina voted overwhelmingly on November 19, 2023, for Javier Milei to become its next president.  President Milei has a fascinating biography, which includes having played goalie for the Club Atlético Chacarita junior team, sung for the Rolling Stones cover band Everest, taught economics in universities for more than two decades, and hosted his own radio show.  Even more fascinating, however, are his dogs.  As of his election as president, he had five English Mastiffs.  Not only are four named for Milei's favourite three economists (that is, Milton Friedman, Murray Rothbard, and Robert Lucas), they are also reputed to be clones of his first English Mastiff, Conan.

It may or may not be true that all politicians are alike.  However, Milei's English Mastiffs are all extremely similar, which is unsurprising given their apparent provenance as clones.

Medicine's CRISPR Focus

 The United Kingdom Medicines and Healthcare products Regulatory Agency ("MHRA") made history today when it approved the medicine "Casgevy" for the treatment of sickle-cell disease and transfusion-dependent β-thalassemia in patients aged 12 and older.  As the MHRA announced in a press release,

Casgevy is the first medicine to be licensed that uses the innovative gene-editing tool CRISPR, for which its inventors were awarded the Nobel Prize in 2020.  

Both sickle cell disease and β-thalassemia are genetic conditions caused by errors in the genes for haemoglobin, which is used by red blood cells to carry oxygen around the body. Sickle cell disease is particularly common in people with an African or Caribbean family background. β-thalassemia mainly affects people of Mediterranean, south Asian, southeast Asian and Middle Eastern origin. 

In people with sickle cell disease, this genetic error can lead to attacks of very severe pain, serious and life-threatening infections, and anaemia (whereby your body has difficulty carrying oxygen). 

In people with β-thalassaemia, it can lead to severe anaemia. Patients often need a blood transfusion every 3 to 5 weeks, and injections and medicines throughout their lives. 

Casgevy is designed to work by editing the faulty gene in a patient’s bone marrow stem cells so that the body produces functioning haemoglobin. To do this, stem cells are taken out of bone marrow, edited in a laboratory and then infused back into the patient after which the results have the potential to be life-long. 

Here's how Casgevy, developed by Vertex Pharmaceuticals in Boston, Massachusetts, and CRISPR Therapeutics in Zug, Switzerland, works:

Casgevy is administered by taking stem cells out of a patient’s bone marrow and editing a gene in the cells in a laboratory. Patients must then undergo conditioning treatment to prepare the bone marrow before the modified cells are infused back into the patient. After that, patients may need to spend at least a month in a hospital facility while the treated cells take up residence in the bone marrow and start to make red blood cells with the stable form of haemoglobin.

Sickle-cell disease and transfusion-dependent β-thalassemia are painful and debilitating conditions that disproportionately afflict the poor.  Casgevy marks a landmark, heralding the beginning of CRISPR-based therapeutics approved for the market, and, more importantly, for the treatment of patients.