U.S. poised to approve breakthrough treatment

Joe Tsogbe had his first hip replacement surgery when he was 19 years old. In his 20s, he was hospitalized on average about nine times a year. By his 30s, that number had grown to more than a dozen.

All of these are caused by sickle cell disease, a genetic mutation that causes red blood cells that are normally full-moon shaped to become crescent-shaped and get stuck in blood vessels, restricting blood flow and causing bouts of severe pain. It's a blood disease.

The disease affects approximately 100,000 people in the United States, many of whom are Black. There are few treatments available, and the only treatment is a bone marrow transplant, in which patients receive healthy blood stem cells from a donor. New gene therapies aim to alleviate symptoms while eliminating the need to trace donors.

Tsogbe, now 37, received one of the options known as exa-cel, co-developed by Vertex Pharmaceuticals and CRISPR Therapeutics, in a clinical trial in 2021. This treatment uses a Nobel Prize-winning technology called CRISPR to edit a person's DNA and reduce the symptoms of sickle cell disease.

U.S. regulators are expected to approve Exacel for use in sickle cell patients by the end of this week. The UK approved it last month under the trade name Kasugebi.

U.S. regulators are also considering another gene therapy from Bluebird Bio called lovo-cel. Although its action is different from exa-cel, the method of administration is similar and it is also aimed at eliminating the pain crisis. It is expected to be approved by the end of this month.

The U.S. Food and Drug Administration's approval of exa-cel is a scientific milestone nearly a decade after the discovery of CRISPR, and a milestone for patients desperate for better options.

Wall Street is also eyeing a price tag of about $2 million per patient, which could be a major test for the U.S. health care system. Tens of thousands of people could qualify.

In 2012, researchers Jennifer Doudna and Emmanuel Charpentier published a seminal paper on a gene editing system called CRISPR-Cas9. The discovery led to a flurry of companies trying to use the insights to treat a variety of diseases.

Sickle cells emerged as the main target.

Scientist Linus Pauling described sickle cell as the first molecular disease in 1949. The disease is most common in Africa, where the sickle cell gene helped protect against malaria. A person who has one copy of the mutation usually has no symptoms of the disease, but a person who has one copy of the mutation from each parent, meaning he has two copies, can develop severe complications. There is a gender.

Editing a patient's genes through CRISPR technology could turn on so-called fetal hemoglobin, a protein that normally stops functioning shortly after birth, allowing red blood cells to maintain a healthy shape. And that work can also be done in the lab. Blood stem cells are extracted, edited, and then injected into the patient's bloodstream.

“We're more or less training the cells to express and produce more of this fetal hemoglobin,” says E.K., director of blood and bone marrow transplantation at NewYork-Presbyterian/Columbia University Irving Medical Center and director of blood and bone marrow transplantation at NewYork-Presbyterian/Columbia University Irving Medical Center. said Dr. Marcus Mapara, who treated the patient. -Cell trial version.

Although the treatment itself only requires one visit, the entire process can take several months.

After the blood stem cells are extracted and isolated, they are sent to Vertex's lab, where they are genetically modified. Once ready, patients undergo several days of chemotherapy to remove old cells and make space for new ones. After the new cells are injected, the recipient spends several weeks recovering in the hospital.

Vertex and CRISPR signed an agreement in 2015 to jointly develop gene editing treatments for genetic diseases including sickle cell. As part of the agreement, Vertex will lead the launch of exa-cel, pending approval.

Vertex sees exa-cel as a multi-billion dollar opportunity. The company plans to focus on the roughly 32,000 people in the U.S. and Europe with the most severe forms of the disease, like Tsogbe.

Vertex is also seeking approval to use Exacell to treat another blood disease called beta-thalassemia. An FDA decision is expected in March.

But Wall Street is skeptical that exa-cel will become big business. Analysts expect Vertex's Exercell sales to be $1.2 billion in 2028, a fraction of the company's overall projected sales of $14 billion for the same year, according to FactSet.

Mapala says it's too early to call Exacel a cure, but points to a graph of prospective patients in the clinical trial that shows the number of pain symptoms people experienced before and after treatment. For most participants, the new number is zero.

“It's amazing,” said Mapala, a paid consultant for Vertex and CRISPR. “We'll see how effective this treatment really is.”

However, the long treatment period and the risk of infertility caused by chemotherapy may make Exacel a difficult option for some patients. In addition, availability may be further limited as it is only available in a limited number of specialized medical facilities. And it costs money too.

Wall Street expects Vertex to charge about $2 million per patient for treatment. That doesn't make Exercel the most expensive gene therapy, with recently approved treatments costing more than $3 million per person. But it may be available to tens of thousands of more patients than other gene therapies, which could make insurers reluctant to broadly cover it.

For Tsogbe, any cost is worth it.

As a baby in the West African country of Togo, Tsogbe cried as her fingers, toes, knees and other joints swelled. His mother took him to multiple doctors until a specialist diagnosed Tsogbe with sickle cell disease. There weren't many treatments available at the time.

But Tsogbe promised her mother that she would go to the United States and find a cure for sickle cell so she wouldn't get sick again. He immigrated to the United States at the age of 16 and eventually found his exa-cel trial.

Since receiving treatment about two years ago, I have not experienced a single episode of pain. It doesn't erase the damage his body had already accumulated, nor does it completely eliminate his aches and pains. But it kept him away from the hospital and made him busier than ever. He runs his two entertainment companies and teaches dance. He always loved, but he used to be exhausted.

Last year, he returned to Togo to see his mother for the first time since leaving in 2003 and, in his words, became a completely different person.

“In a way, I kept my promise,” Tsogbe said.

— CNBC Patrick Manning contributed to this report.