The First Crispr Medicine Just Got Approved

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https://www.wired.com/story/crispr-gene-therapy-approved-sickle-cell-casgevy/

EMILY MULLIN
SCIENCE
NOV 16, 2023 10:32 AM

The First Crispr Medicine Just Got Approved​

The gene-editing therapy, called Casgevy, uses Crispr to prevent debilitating pain in patients with sickle cell disease. It also eliminates the need for regular blood transfusions in people with beta thalassemia.

ILLUSTRATION: ANDY/GETTY IMAGES

The first medical treatment that uses Crispr gene editing was authorized Thursday by the United Kingdom.

The one-time therapy, which will be sold under the brand name Casgevy, is for patients with sickle cell disease and a related blood disorder called beta thalassemia, both of which are inherited. The UK approval marks a historic moment for Crispr, the molecular equivalent of scissors that won its inventors a Nobel Prize in 2020.

Developed by Vertex Pharmaceuticals of Boston and Crispr Therapeutics of Switzerland, Casgevy is meant to prevent episodes of excruciating pain that are typical of sickle cell disease and free people with beta thalassemia of regular blood transfusions. The treatment involves editing a patient’s own cells outside the body and infusing them back in. For some, the therapy may even be a cure.

“This is just the start of Crispr therapies. There are a lot more to come,” says Samarth Kulkarni, chairman and CEO of Crispr Therapeutics. Adapted from a naturally occurring defense system found in bacteria, Crispr is being investigated as a way to treat a range of other genetic conditions, as well as certain types of cancers and even HIV. It works by making targeted cuts in DNA.

Europe and the United States are poised to approve the Crispr therapy soon as well. The US Food and Drug Administration has until December 8 to make a decision. On October 31, an advisory committee to the FDA concluded that the treatment was safe for patients.

The authorization from the UK Medicines and Healthcare products Regulatory Agency is for sickle cell patients with recurrent pain crises and for those with the most serious form of beta thalassemia who are 12 years and older. Vertex and Crispr Therapeutics estimate that about 2,000 people in the UK are eligible for the therapy.

The UK agency greenlit the groundbreaking treatment after “a rigorous assessment of its safety, quality and effectiveness,” it said in a statement. However, the approval is conditional for one year. Vertex and Crispr Therapeutics will need to provide more data on the therapy’s safety and efficacy for it to remain available.

Both sickle cell disease and beta thalassemia are genetic conditions caused by errors in the genes for hemoglobin, the vital protein found in red blood cells that carries oxygen throughout the body. Sickle cell disease disproportionately affects people of African and Caribbean descent, while beta thalassemia mainly affects people of Mediterranean, South Asian, Southeast Asian, and Middle Eastern origin.

In sickle cell disease, abnormal hemoglobin makes a person’s blood cells hard and crescent-shaped. These misshapen cells clump together and block blood flow to organs, causing bouts of extreme pain. The cells then die off early, leaving a lack of healthy red blood cells, or anemia.

Beta thalassemia also causes anemia because the body makes less hemoglobin than normal.

People with life-threatening beta thalassemia need blood transfusions every three to five weeks and other medications throughout their lifetime.

“Both sickle cell disease and beta thalassemia are painful, lifelong conditions that in some cases can be fatal,” said Julian Beach, interim executive director of healthcare quality and access at the UK’s MHRA, on Thursday.

Casgevy is meant to restore working hemoglobin in the body. The therapy is not a traditional drug. Rather, it involves a complicated procedure. A patient’s stem cells are collected from their bone marrow and then sent to a lab for manufacturing. There, scientists use Crispr to make an edit in a gene that’s meant to turn on a functioning version of hemoglobin.

Patients must then undergo a conditioning treatment to prepare their bone marrow to receive the modified cells. Afterward, they may need to spend a month or more in a hospital while the edited cells take up residence in the bone marrow and start to make healthy red blood cells.

In a trial run by Vertex and Crispr Therapeutics, 45 patients have been treated with Casgevy but only 29 have been followed for at least 18 months. Of those, 28 were free of severe pain crises for at least a year after treatment.

In a study of beta thalassemia patients, 54 patients have so far received Casgevy. Of 42 that have been followed long enough, 39 did not need a blood transfusion for at least a year after treatment. The remaining three had more than a 70 percent reduction in the need for transfusions. Side effects of the treatment include nausea, fatigue, fever, and increased risk of infection. Both trials are ongoing.

Because Crispr is designed to permanently alter the genome, scientists think the effects could last for years, if not decades.

Currently, sickle cell disease can be cured with a bone marrow transplant from a closely matched tissue donor, but only about 20 percent of patients have one. Transplants are also risky and may not work. They can cause a life-threatening complication in which the donor stem cells attack the recipient’s body.

Vertex and Crispr Therapeutics have not announced a price for the therapy, but it’s likely to be expensive. Vertex says it is working closely with national health authorities in the US to secure access for eligible patients as quickly as possible.

 

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https://www.reuters.com/business/healthcare-pharmaceuticals/uk-authorises-gene-therapy-blood-disorders-world-first-2023-11-16/

UK authorises gene therapy for blood disorders in world first​

Reuters
November 16, 202310:59 AM ESTUpdated a day ago

A sign hangs in front of the world headquarters of Vertex Pharmaceuticals in Boston, Massachusetts, U.S., October 23, 2019. REUTERS/Brian Snyder Acquire Licensing Rights

• Companies

• CRISPR Therapeutics AG
• Vertex Pharmaceuticals Inc

LONDON, Nov 16 (Reuters) - Britain has authorised a gene therapy that aims to cure sickle-cell disease and another type of inherited blood disorder for patients aged 12 and over, the country's medical regulator said on Thursday, becoming the first in the world to do so.

Casgevy is the first medicine to be licensed that uses the gene-editing tool CRISPR, which won its inventors the Nobel Prize in 2020, Britain's Medicines and Healthcare products Regulatory Agency (MHRA) said.

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.

"Both sickle cell disease and β-thalassemia are painful, life-long conditions that in some cases can be fatal," MHRA Interim Director Julian Beach said in the statement.

In clinical trials Casgevy has been found to restore healthy haemoglobin production in the majority of participants with sickle-cell disease and transfusion-dependent β -thalassaemia, relieving the symptoms of disease, Beach added.

The MHRA said no significant safety concerns were identified during the trials, adding that it was closely monitoring the safety of the medicine.

The medicine is administered by taking stem cells out of a patient’s bone marrow and editing a gene in the cells in a laboratory, with the modified cells then infused back into the patient after conditioning treatment to prepare the bone marrow.

U.S.-based companies Vertex Pharmaceuticals (VRTX.O) and CRISPR Therapeutics (CRSP.BN) welcomed the approval in a separate statement.

"I hope this represents the first of many applications of this Nobel Prize winning technology to benefit eligible patients with serious diseases," said CRISPR CEO Samarth Kulkarni said.

Reporting by Muvija M; editing by Sarah Young

 

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[Professor Emeritus]

It's interesting because they're editing the cells outside the body and then putting them back in. Which at least lowers the likelihood of accidentally damaging other cells in the body.

Still doesn't fully eliminate the possibility that something bad will happen in the long term to the edited cells, but I'm sure a lot of people with sicker cell would take the chance. I lost a former student to that shyt when he was just 22.

 

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[Serious]

@krackdagawd

 

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I received the new gene-editing drug for sickle cell disease. It changed my life.

As a patient enrolled in a clinical trial for Vertex’s new exa-cel treatment, I was among the first to experience CRISPR’s transformative effects.

www.technologyreview.com

I received the new gene-editing drug for sickle cell disease. It changed my life.​

As a patient enrolled in a clinical trial for Vertex’s new exa-cel treatment, I was among the first to experience CRISPR’s transformative effects.

By

• Jimi Olaghere archive page

December 4, 2023

MATT ODOM

On a picturesque fall day a few years ago, I opened the mailbox and took out an envelope as thick as a Bible that would change my life. The package was from Vertex Pharmaceuticals, and it contained a consent form to participate in a clinical trial for a new gene-editing drug to treat sickle cell disease.

A week prior, my wife and I had talked on the phone with Haydar Frangoul, an oncologist and hematologist in Nashville, Tennessee, and the lead researcher of the trial. He gave us an overview of what the trial entailed and how the early participants were faring. Before we knew it, my wife and I were flying to the study site in Nashville to enroll me and begin treatment. At the time, she was pregnant with our first child.

I’d lived with sickle cell my whole life—experiencing chronic pain, organ damage, and hopelessness. To me, this opportunity meant finally taking control of my life and having the opportunity to be a present father.

The drug I received, called exa-cel, could soon become the first CRISPR-based treatment to win approval from the US Food and Drug Administration, following the UK’s approval in mid-November. I’m one of only a few dozen patients who have ever taken it. In late October, I testified in favor of approval to the FDA’s advisory group as it met to evaluate the evidence. The agency will make its decision about exa-cel no later than December 8.

Related Story​

The first CRISPR cure might kickstart the next big patent battle


Vertex Pharmaceuticals plans to sell a gene-editing treatment for sickle-cell disease. A patent on CRISPR could stand in the way.

I’m very aware of how privileged I am to have been an early recipient and to reap the benefits of this groundbreaking new treatment. People with sickle cell disease don’t produce healthy hemoglobin, a protein that red blood cells use to transport oxygen in the body. As a result, they develop misshapen red blood cells that can block blood vessels, causing intense bouts of pain and sometimes organ failure. They often die decades younger than those without the disease.

After I received exa-cel, I started to experience things I had only dreamt of: boundless energy and the ability to recover by merely sleeping. My physical symptoms—including a yellowish tint in my eyes caused by the rapid breakdown of malfunctioning red blood cells—virtually disappeared overnight. Most significantly, I gained the confidence that sickle cell disease won’t take me away from my family, and a sense of control over my own destiny.

Today, several other gene therapies to treat sickle cell disease are in the pipeline from biotech startups such as Bluebird Bio, Editas Medicine, and Beam Therapeutics as well as big pharma companies including Pfizer and Novartis—all to treat the worst-suffering among an estimated US patient population of about 100,000, most of whom are Black Americans.

But many people who need these treatments may never receive them. Even though I benefited greatly from gene editing, I worry that not enough others will have that opportunity. And though I’m grateful for my treatment, I see real barriers to making these life-changing medicines available to more people.

A grueling process​

I feel very fortunate to have received exa-cel, but undergoing the treatment itself was an intense, monthslong journey. Doctors extracted stem cells from my own bone marrow and used CRISPR to edit them so that they would produce healthy hemoglobin. Then they injected those edited stem cells back into me.

It was an arduous process, from collecting the stem cells, to conditioning my body to receive the edited cells, to the eventual transplant. The collection process alone can take up to eight hours. For each collection, I sat next to an apheresis machine that vigorously separated my red blood cells from my stem cells, leaving me weakened. In my case, I needed blood transfusions after every collection—and I needed four collections to finally amass enough stem cells for the medical team to edit.

The conditioning regimen that prepared my body to receive the edited cells was a whole different challenge. I underwent weeks of chemotherapy to clear out old, faulty stem cells from my body and make room for the newly edited ones. That meant dealing with nausea, weakness, hair loss, debilitating mouth sores, and the risk of exacerbating the underlying condition.

MATT ODOM

My transplant day was in September 2020. In a matter of minutes, a doctor transferred the edited stem cells into me using three small syringes filled with clear fluid. Of course, the care team did a lot to try and make it a special day, but for me that moment was honestly deflating.

However, the days and months since have been enriching. I’ve escaped from the clutch of fear that comes from thinking every occasion could be my last. Noise and laughter from my 2-year-old twin daughters and 4-year-old son echo through my home, and I’ve gained immense confidence from achieving my goal of being a father.

It’s clear to me from my experience that this treatment is not made for everyone, though. To receive exa-cel, I spent a total of 17 weeks in the hospital. Not everyone will want to subject themselves to such a grueling process or be able to take time away from family obligations or work. And my treatment was free as part of the trial—if approved, exa-cel could cost millions of dollars per patient.

Another potential barrier is that some people become enmeshed with their chronic disease. In many ways, your disease becomes part of your identity and way of life. The community of people with sickle cell disease—we call ourselves warriors—is a source of strength and support for many. Even the promise of a better life from a novel technology may not be strong enough to break that bond.

From few, to many​

Other challenges are society-wide. In advancing new treatments, the US medical industrial complex has too often left a trail of systemic racism and unethical medical practices in its wake. As a result, many Black Americans mistrust the medical system, which could further suppress turnout for new gene therapies.

Related Story​

Three people were gene-edited in an effort to cure their HIV. The result is unknown.



CRISPR is being used in an experimental effort to eliminate the virus that causes AIDS.

Global accessibility has also not been a priority for most of the companies developing these new treatments, which I feel is a mistake. Some have cited the lack of health-care infrastructure in sub-Saharan Africa, which houses about 80% of all sickle cell disease cases globally. But that just sounds to me like a convenient excuse.

The options for treating sickle cell disease are very limited. Denying access to such a powerful and transformative treatment based on someone’s ability to pay, or where they happen to live, strikes me as unethical. I believe patients and health-care providers everywhere deserve to know that the treatment will be available to those who need it.

Conducting gene therapy research and clinical trials in African populations could allow for a more comprehensive understanding of the genetic diversity of sickle cell disease. This knowledge may even contribute to the development of more effective and tailored therapies—not only for Africans, but also for people of African descent living in other regions.

Even as a direct beneficiary of gene therapy, I often struggle with not knowing the full consequences of my actions. I fundamentally, at a cellular level, changed who I am. Where do we draw the line at playing God? And how do we make the benefits of a God-like technology such as this more widely available?

Jimi Olaghere is a patient advocate and tech entrepreneur.