Gene-editing kicked off 2024 with a bang in the medical sector but closed the year with a whimper. It started with the FDA approval for the first CRSPR-based gene therapy treatment for sickle cell anemia (SCA) called Casgevy, developed by Vertex Pharmaceuticals Inc. (NASDAQ: VRTX). Sickle cell is a disease that causes red blood cells to form into a sickle-like shape, which can block blood flow, leading to more serious complications like pain and organ damage. It is caused by a mutation in the hemoglobin gene (HBB). CRISPR-Cas9 acts as molecular scissors that can precisely snip out parts of the HBB genome in living cells. To remedy sickle cells, CRISPR-Cas9 is used to edit genes that inhibit the production of BCL11A, which reactivates rich fetal hemoglobin production to reduce the sickling of blood cells.

CRISPR Therapeutics: Helping Develop Casgevy

While Vertex Pharmaceuticals took Casgevy to market, CRISPR Therapeutics AG (NASDAQ: CRSP) was a key collaborator in the development of the treatment, which had a 93.5% effective rate for treating SCD patients with recurrent vaso-occlusive crises (VOCs). This motivated CRISPR to seek treatments for a whole universe of hereditary diseases, kicking off the gene-editing race and surging its shares up to $91.10 by the first week of February 2024. Unfortunately, shares sank to close the year down 34% in 2024.

The Cut and Paste Tool For Gene-Editing

The technology is still in its infancy and extremely expensive at $2.2 million a treatment. A patient would only need a single treatment. CRISPR-Cas9 is comprised of two parts. A guide RNA will target the specific sequence within the genome, and Cas9 will be used as the molecular scissors that will precisely cut out the targeted sequence. It enables scientists to edit the remaining genome by modifying, inserting, or deleting new sequences, making CRISPR-Cas9 a cut-and-paste tool for gene editing.

Greater Than 90% Success Rate and More Treatments to Come

Vertex Pharmaceutical presented impressive long-term data for its Casgevy treatment. 39 out of 42 patients with SCD were free from VODs for at least 12 consecutive months, with a mean duration of VIC-free status of 30.9 months. The success rate for patients with transfusion-dependent beta-thalassemia (TDT) was 98% or 53 out of 54. These patients went at least 12 consecutive months of transfusion independence with a weighted average hemoglobin of at least 9/gdL.

The mean duration of transfusion independence was 34.5 months, with a maximum of 64.1 months. Over 45 authorized treatment centers have been activated worldwide to support Casgevy therapy, and over 40 patients have had their first cell collections.

CRISPR Therapeutics is pursuing treatments for cystic fibrosis. Duchenne Muscular Dystrophy (DMD), hemophilia A and B, HIV, inherited retinal disease (IRD). CRISPR expects its cardiovascular disease treatments CTX310 and CTX320 top-line results to be present in 2025. The company has $1.9 billion in cash, which can sustain it for over three more years until a capital raise is needed, but the company expects profitability by 2028.

Intellia Therapeutics: Gene-Editing to Treat Cancer and Genetic Diseases

Another leader in gene editing is Intellia Therapeutics Inc. (NASDAQ: NTLA), which focuses on treating genetic diseases, while CRISPR Therapeutics focuses on hereditary blood disorders. Intellia also uses CRISPR-Cas9 treatments to address a broader pipeline of therapies for hereditary angioedema (HAE), alpha-1 antitrypsin deficiency (AATD), and ATTD-Lung Disease. The company is collaborating with biotech giant Regeneron Pharmaceuticals Inc. (NASDAQ: REGN) for transthyretin amyloidosis (ATTR) and Hemophilia A/B treatments.

Many Catalysts for Top-Line Results in 2025

Intellia reported a Q3 2024 EPS loss of $1.34, which still beat the consensus estimate by 5 cents. Revenue fell 24.1% year-over-year to $9.1 million, beating consensus estimates for $8.28 million. The company received IND clearance from the FDA for its MAGNITUDE-2 Phase 3 study.

The company reported unprecedented positive Phase 2 results for NTLA-2002 to be a functional cure for HAE. Current treatment options are limited to chronically administered prophylactic therapies to manage attacks and on-demand therapies to control breakthrough attacks. The company is actively screening for the Phase 3 HAELO study for NTLA-2002.

Intellia CEO John Leonard commented, “With three active Phase III studies expected by year-end, we are leading the field of in vivo CRISPR-based medicines. Intellia is ushering in a new era of medicine with the prospect of a functional cure for patients suffering from HAE and a treatment that may change the course of the disease for people with ATTR Amyloidosis.”