The First CRISPR Medicine Is Approved. The Hard Part Is Who Gets It.

DISPATCH — DECEMBER 2023 THE FIRST CRISPR MEDICINE IS APPROVED. THE HARD PART IS WHO GETS IT. TL;DR In December 2023, the FDA approved two "one-time" gene therapies for sickle cell disease (SCD) in patients aged 12 and older: - CASGEVY (exagamglogene autotemcel): the first FDA-approved therapy to use CRISPR/Cas9 genome editing. - LYFGENIA (lovotibeglogene autotemcel): a gene therapy that adds a modified gene using a lentiviral vector to produce a modified hemoglobin (HbAT87Q) designed to reduce sickling. Sickle cell disease affects about 100,000 people in the U.S. and is most common in African Americans (and also affects Hispanic Americans). It causes painful vaso-occlusive events/crises (VOEs/VOCs) and can lead to organ damage and early death. This was a rare moment when "breakthrough" is not marketing language. It is a regulatory fact. — 1) WHAT HAPPENED On December 8, 2023, the U.S. FDA approved two milestone treatments for sickle cell disease (SCD) in patients aged 12 and older: - CASGEVY (exagamglogene autotemcel): the first FDA-approved therapy to use CRISPR/Cas9 genome editing. - LYFGENIA (lovotibeglogene autotemcel): a gene therapy that adds a modified gene using a lentiviral vector to produce a modified hemoglobin (HbAT87Q) designed to reduce sickling. Sickle cell disease affects about 100,000 people in the U.S. and is most common in African Americans (and also affects Hispanic Americans). It causes painful vaso-occlusive events/crises (VOEs/VOCs) and can lead to organ damage and early death. This was a rare moment when "breakthrough" is not marketing language. It is a regulatory fact. — 2) WHY THIS IS A REAL TECHNOLOGY SHIFT (NOT A SMALL UPGRADE) These therapies are not new pills. They re-engineer your own blood stem cells and try to make your body produce hemoglobin in a way that prevents sickling. CASGEVY (CRISPR route) - Doctors collect a patient's blood stem cells. - Those cells are edited outside the body using CRISPR/Cas9. - The edited cells are infused back so they can repopulate the bone marrow and increase fetal hemoglobin (HbF), which helps prevent sickling. LYFGENIA (gene-addition route) - Doctors collect a patient's blood stem cells. - The cells are modified with a lentiviral vector (a gene delivery vehicle) to produce a modified hemoglobin (HbAT87Q) designed to reduce sickling. - The modified cells are infused back to repopulate the marrow. The headline isn't "gene therapy exists." The headline is: the U.S. now has approved, industrialized pathways for editing or rewriting blood at scale. This is a new platform era. — 3) THE PART THAT DOESN'T FIT IN HEADLINES: THIS IS A TRANSPLANT-LIKE EXPERIENCE Both therapies are "one-time" infusions, but the process is not one-time effort. Before a patient receives the edited/modified cells, they must undergo myeloablative conditioning: high-dose chemotherapy that clears the bone marrow so the new cells can engraft. In other words: the treatment is built on a serious medical trade: - You accept chemotherapy risk and a long clinical course - in exchange for the possibility of long-term freedom from painful crises This is why "cure" talk needs discipline. Even when the outcomes are strong, the road to the outcome is intense. The ethical point: A therapy that is medically miraculous but operationally brutal will always create unequal access unless the system bends around the patient. — 4) THE MONEY QUESTION: A BREAKTHROUGH WITH A MULTIMILLION DOLLAR DOOR FEE These therapies launched with list prices reported in the millions: - CASGEVY: $2.2 million (U.S. list price reported at approval) - LYFGENIA: $3.1 million (U.S. list price reported at approval) "High cost" is not just a headline problem. It's a deployment problem: - Hospitals need reimbursement certainty before offering it. - Insurers decide who qualifies and what hoops exist. - Families face indirect costs: travel, time off work, months of care coordination. Sickle cell has also been historically underfunded relative to its burden, and it disproportionately affects Black patients in the U.S. That history turns price into an equity test: does the system show up now that the science has? If the answer is "only for a narrow slice," then the breakthrough becomes a status symbol instead of a public health win. — 5) SAFETY REALITY: LONG-TERM MONITORING IS PART OF THE DEAL The FDA requires long-term follow-up to evaluate safety and effectiveness after these approvals. Important detail: LYFGENIA carries a black box warning for hematologic malignancy (blood cancer). Lifelong monitoring is recommended for that risk. CASGEVY's trial results were strong, but long-term real-world data always lags approvals in first-of-kind therapies. That's not scandal. That's how medicine works. The ethical responsibility is to keep the public narrative aligned with what is known versus what is hoped. In the first platform therapies, the "unknown unknowns" matter. — 6) WHO BENEFITS VS WHO PAYS (ACCOUNTABILITY BOX) MOST HELPED (IF THE SYSTEM WORKS) - People with severe, recurrent painful crises who may gain long-term relief. - Families and caregivers who live around unpredictable emergencies. - Clinicians who finally have an option beyond chronic management and limited donorTransplants. MOST EXPOSED (FIRST) - Patients who must undergo chemotherapy and months of medical disruption to access the therapy. - Communities already underserved by specialist access and advanced centers. - Patients whose insurance and geography decide their medical future. QUIET WINNERS - Biotech platforms and investors, because "first CRISPR approval" validates a whole industry. - High-resource hospitals that can scale advanced cellular workflows. QUIET LOSERS - Patients in regions without transplant infrastructure. - The global South, where sickle cell burden can be high but "multimillion dollar autologous cell therapy" is structurally out of reach. - Anyone who will be told "a cure exists," while being unable to access it. — 7) WHAT WE SHOULD DEMAND NEXT (SO THIS DOESN'T BECOME "RICH CURE, POOR DISEASE") A) ACCESS AS A PRODUCT REQUIREMENT Approval is step one. The real milestone is: can patients actually receive it without years of delay? B) TRANSPARENT COVERAGE CRITERIA If insurers gatekeep, the rules should be public and consistent. "Case-by-case" becomes inequality by default. C) OUTCOME-BASED PAYMENTS DONE RIGHT If the system wants "pay for performance," it must protect patients from becoming finance instruments. Outcomes tracking should not become surveillance. D) MORE TREATMENT CENTERS + SUPPORT PIPELINES These therapies require specialized centers. Scaling centers, training teams, and supporting travel/lodging is part of ethical deployment. E) NEXT-GEN VERSIONS THAT REDUCE CHEMO BURDEN The high-dose chemo step is a major barrier. The most ethical future version of this platform is not only "cheaper," but "less brutal." F) GLOBAL HEALTH HONESTY A therapy can be revolutionary and still inaccessible globally. If this platform is the future, the moral work is to make future generations of it scalable beyond wealthy health systems. — 8) THE AUGMENTED HUMAN TEST A "cure" is not just a molecule or an edit. A cure is an infrastructure event. If we treat this approval as a finish line, we'll get a world where the cure exists and the disease still destroys lives because access is rationed. If we treat it as a beginning, we can build a future where cutting DNA is not the hardest part. No hype. Just consequences.