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‘Monumental’: FDA approves first CRISPR-based gene-editing drug, marking breakthrough for sickle cell disease

FDA approves first gene-editing therapy
WATCH: The breakthrough treatment, made by local drug firms, targets sickle cell disease. Reporter Jonathan Saltzman breaks down the life-changing medicine.

The Food and Drug Administration on Friday approved the first drug in the United States to use the revolutionary gene-editing tool called CRISPR-Cas9, a historic action that pushes medicine and biotechnology across another frontier as researchers seek cures for diseases from cancer to heart conditions.

The new medicine, marketed as Casgevy, treats sickle cell disease, a long-neglected blood disorder that causes crushing pain and mostly afflicts people of African descent.

Casgevy was developed by Boston-based Vertex Pharmaceuticals and CRISPR Therapeutics, which is headquartered in Zug, Switzerland, but has most of its workforce in Massachusetts. It uses a method to edit DNA first described in a landmark scientific paper 11 years ago by two authors who would win a Nobel Prize in chemistry.

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The FDA also approved a rival sickle cell treatment called Lyfgenia, developed by Somerville-based Bluebird Bio, that hadn’t been expected to gain approval until Dec. 20. Lyfgenia is a gene therapy that uses an engineered virus to insert a modified gene into the DNA of a patient’s blood stem cells. The FDA has approved at least eight gene therapies for mostly rare diseases since 2017.

“Sickle cell disease is a rare, debilitating, and life-threatening blood disorder with significant unmet need,” said Dr. Nicole Verdun, director of the Office of Therapeutic Products in the FDA’s Center for Biologics Evaluation and Research. “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.”

Regulators approved the medicines for patients 12 years of age and older with pain crises caused by their disease.

Both drugs are delivered through one-time infusions and are among the most expensive medicines ever approved. Lyfgenia will cost $3.1 million per patient, while Casgevy will cost $2.2 million per patient.

The price tags exceed estimates from an independent Boston-based drug-pricing watchdog group of their maximum reasonable cost. The Institute for Clinical and Economic Review, or ICER, calculated that prices for both drugs could reach nearly $2 million and be fair, given the cumulative costs of treating sickle cell over a lifetime and the benefits the new medicines would bring to patients and families.

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Dr. David Rind, ICER’s chief medical officer, said Friday that Casgevy is “close to the upper bound of ICER’s estimate of a fair price” but Lyfgenia is “substantially higher than what ICER feels would be a fair price.”

Vertex and Bluebird, however, contended the benefits from their drugs outweigh their high prices. The companies estimated that the lifetime health care cost in the United States for treating sickle cell patients with recurring pain crises was $4 million to $6 million.

Advocates for makers of gene-based drugs said people need to compare such transformative medicines to major medical procedures — not to ordinary drugs.

“A heart transplant costs about $1.6 million,” said Timothy Hunt, chief executive of the Alliance for Regenerative Medicine, an industry-backed advocacy group in Washington, D.C. “These one-time medical interventions can be expensive, but they create enormous value for patients and society.”

Public and private insurers typically pay most of the expenses of FDA-approved medicines, including those of recently cleared multimillion-dollar gene-based treatments. A spokesperson for the federal Centers for Medicare and Medicaid Services said Friday the government insurer “is committed to ensuring that people with serious medical conditions” such as sickle cell disease “have access to innovative treatments.”

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Sickle cell causes round flexible red blood cells that carry oxygen to deform into a sickle shape and stick to vessel walls. That deprives tissues of oxygen, causing crippling pain that can only be relieved with opioids and blood transfusions. The disorder can also lead to strokes, damage organs, and cause early death.

About 100,000 Americans, most of them people of color, are believed to have the condition. The Vertex-CRISPR treatment was geared for the 20 percent of patients who are 12 and older and have repeated pain crises that can’t be relieved by other sickle cell drugs. That’s roughly 16,000 people in the US, according to Vertex

In a clinical trial, Casgevy completely relieved 29 of 30 sickle cell patients of episodes of excruciating pain for at least one year among participants who were followed for at least 18 months, according to Vertex. The patients received a one-time intravenous infusion of edited stem cells that flipped a genetic switch to restore their blood cells’ ability to carry oxygen throughout their bodies.

Lyfgenia also proved remarkably effective in a clinical trial run by Bluebird. However, the FDA imposed a black box warning on the instructions for use of the drug because some patients treated in the trial suffered blood cancers, a known risk of gene therapies.

The first hospital in Boston to make the two treatments available is expected to be Boston Medical Center. That hospital has a caseload of roughly 600 adult and pediatric sickle cell patients, more than any other in New England, according to Dr. Jean-Antoine Ribeil, clinical director of the Center of Excellence in Sickle Cell Disease there. Roughly 70 to 80 percent of patients at the hospital are covered by the government heath insurance programs Medicare and Medicaid, Ribeil said.

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The first hospital in Boston to make the newly approved treatment for sickle cell disease available will be Boston Medical Center, according to Vertex Pharmaceuticals.Jessica Rinaldi/Globe Staff

Ribeil estimated that five to 10 adult sickle cell patients at BMC should be able to get Casgevy and Lyfgenia next year. Both medicines require several months of preparation, including a grueling regimen of chemotherapy to make room in patients’ blood marrow for genetically edited or modified stem cells.

“This is monumental,” Ribeil said of the approval of Casgevy. “It’s just huge to have this CRISPR treatment only [11] years after this scientific discovery.”

Rahman Oladigbolu, a 52-year-old Harvard-educated filmmaker in Brockton, goes to BMC for treatment of his sickle cell disease, which has caused so much damage that he has had six joints — his hips, shoulders, and knees — surgically replaced. He called the approval of the two gene-based treatments “amazing news.”

Several medical experts and advocates were particularly pleased the first CRISPR-derived treatment to win FDA approval targets sickle cell.

The disease was the first human disorder understood on a molecular level, its underpinnings explained in a seminal 1949 paper written by the future two-time Nobel laureate Linus Pauling. But research on the disease languished for decades afterward, which many experts blame on structural racism, particularly in funding.

Rahman Oladigbolu, a Harvard-educated filmmaker with sickle cell disease who lives in Brockton.Jonathan Wiggs/Globe Staff

An estimated 8 million people around the world live with sickle cell, according to the Institute for Health Metrics and Evaluation at the University of Washington in Seattle.

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The gene-editing method that became known as CRISPR was first reported in a landmark 2012 paper by American biochemist Jennifer Doudna of the University of California, Berkeley, and French microbiologist Emmanuelle Charpentier of the Max Planck Institute for Infection Biology. They would share the 2020 Nobel Prize in chemistry.

CRISPR-based treatments will likely be approved for other disorders in the coming years, experts said, although its hard to predict for what and when. Researchers, including scientists at biotech companies and hospitals in Massachusetts, are studying the potential of gene editing for a variety of diseases, from ALS to diabetes to forms of cancer.


Jonathan Saltzman can be reached at jonathan.saltzman@globe.com.