UK first to approve CRISPR treatment for diseases: what you need to … – Nature.com

Sickle-cell anaemia is marked by red blood cells that are misshapen and sticky, affecting blood flow.Credit: Eye Of Science/SPL

In a world first, the UK medicines regulator has approved a therapy that uses CRISPR gene editing as a treatment for diseases. The decision marks another high point for a biotechnology that has regularly been lauded as revolutionary in the decade since its discovery.

The therapy, called Casgevy, will treat the the blood conditions sickle-cell disease and -thalassaemia. Sickle-cell disease, also known as sickle-cell anaemia, can cause debilitating pain, and people with -thalassaemia can require regular blood transfusions.

This is a landmark approval which opens the door for further applications of CRISPR therapies in the future for the potential cure of many genetic diseases, said Kay Davies, a geneticist at the University of Oxford, UK, in comments to the UK Science Media Centre.

Nature explains the research behind the treatment and explores whats next.

The approval by the Medicines and Healthcare products Regulatory Agency (MHRA) follows promising results from clinical trials that tested the one-time treatment, which is administered by intravenous infusion and was developed by Vertex Pharmaceuticals in Boston, Massachusetts, and CRISPR Therapeutics in Zug, Switzerland.

The trial for sickle-cell disease has followed 29 out of 45 participants long enough to draw interim results. Casgevy completely relieved 28 of those people of debilitating episodes of pain for at least one year after treatment.

Researchers also tested the treatment for a severe form of -thalassaemia, which is conventionally treated with blood transfusions roughly once a month. In this trial, 54 participants received Casgevy and 42 patients have participated for long enough to provide interim results. For at least one year after treatment, 39 participants, or 93% of those treated, did not need a red-blood-cell transfusion. The remaining three people had their need for blood transfusions reduced by more than a 70%.

Casgevy relies on the gene-editing tool CRISPR, the developers of which won the Nobel Prize in Chemistry in 2020.

Sickle-cell disease and -thalassaemia are caused by errors in the DNA sequence of genes that encode for haemoglobin, a molecule that helps red blood cells to carry oxygen around the body.

In sickle-cell disease, abnormal haemoglobin makes blood cells misshapen and sticky, causing them to form clumps that can clog blood vessels. These blockages reduce the oxygen supply to tissues, which can cause periods of severe pain, known as pain crises.

-thalassaemia occurs when mutations in the haemoglobin gene lead to deficient or absent levels of the oxygen-carrying molecule in red blood cells, low numbers of red blood cells and symptoms such as fatigue, shortness of breath and irregular heartbeats.

Clinicians administer Casgevy by taking blood-producing stem cells out of the bone marrow of people with either disease and using CRISPR to edit genes encoding for haemoglobin in these cells. The gene-editing tool an RNA molecule that guides the enzyme to the correct region of DNA and a Cas9 enzyme that cuts DNA.

Once the Cas9 enzyme reaches the gene targeted by Casgevy, called BCL11A, it cuts both DNA strands. BCL11A usually prevents the production of a form of haemoglobin that is made only in fetuses. By disrupting the BCL11A gene, Casgevy unleashes the production of fetal haemoglobin, which does not carry the same abnormalities as adult haemoglobin in people with sickle cell or -thalassaemia patients.

Before the gene-edited cells are infused back into the body, people must undergo a treatment that prepares the bone marrow to receive the edited cells. Once administered, the stem cells give rise to red blood cells containing fetal haemoglobin. After some time, this relieves symptoms by boosting the oxygen supply to tissues. Patients may need to spend at least a month in a hospital facility while the treated cells take up residence in the bone marrow and start to make red blood cells with the stable form of haemoglobin, the MHRA said in a press release.

Participants involved in the trials, which are ongoing, experienced side effects including nausea, fatigue, fever and an increased risk of infection, but no significant safety concerns were identified. The MHRA and manufacturer are monitoring the safety of the technology and will release further results.

One concern surrounding the approach is that CRISPR can sometimes make unintended genetic modifications with unknown side effects.

It is well known that CRISPR can result in spurious genetic modifications with unknown consequences to the treated cells, geneticist David Rueda at Imperial College London told the SMC. It would be essential to see the whole-genome sequencing data for these cells before coming to a conclusion. Nonetheless, this announcement makes me feel cautiously optimistic."

The US Food and Drug Administration is considering approval of Casgevy, whose generic name is exa-cel, for sickle-cell disease; its advisers met last month to discuss the therapy. The European Medicines Agency is also reviewing the treatment for both diseases.

For now, the therapy is likely to remain the reserve of rich nations with developed health-care systems. This treatment may not easily scale up to be able to provide treatments in low- and middle-income countries, since it requires the technology to obtain a patients blood stem cells, deliver the genetic editor to these stem cells, and then reinjection of these cells, geneticist Simon Waddington at University College London told the SMC. It is not an off the shelf medicine that can be readily injected or taken in pill form, he says.

Even in places where it win approval, the high cost of Casgevy is likely to limit who can benefit from it.

The challenge is that these therapies will be very expensive so a way of making these more accessible globally is key, said Davies.

The treatments price has not yet been settled in the United Kingdom, but estimates suggest that it could cost roughly US$2 million per patient, in line with the pricing of other gene therapies.

We have not established a list price for the UK at this time and are focused on working with the health authorities to secure reimbursement and access for eligible patients as quickly as possible, a Vertex spokesperson told Nature.

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UK first to approve CRISPR treatment for diseases: what you need to ... - Nature.com

Sickle-Cell Treatment Created With Gene Editing Wins U.K. Approval – The New York Times

Regulators in Britain on Thursday approved the first treatment derived from CRISPR, the revolutionary gene-editing method. Called Casgevy, the treatment is intended to cure sickle-cell disease and a related condition, beta thalassemia.

The manufacturers, Vertex Pharmaceuticals, based in Boston, and CRISPR Therapeutics, based in Switzerland, say about 2,000 patients in Britain with sickle-cell disease or beta thalassemia are expected to be eligible for its treatment.

The companies anticipate that the Food and Drug Administration will approve Casgevy for sickle-cell patients in the United States in early December. The agency will decide on approval for beta thalassemia next year.

In late December, the F.D.A. is expected to approve another sickle cell gene therapy by Bluebird Bio of Somerville, Mass. That treatment does not rely on gene editing, insteading using a method that inserts new DNA into the genome.

Sickle-cell disease is caused by a defective gene that leads to the creation of abnormal hemoglobin, the oxygen-carrying component in red blood cells. The cells themselves become malformed, causing episodes of extreme pain. About 100,000 Americans, who are mostly Black and Hispanic, are believed to have the illness.

In beta thalassemia, the defective gene leads to deficient levels of hemoglobin in red blood cells. The condition is rare.

Casgevy relies on CRISPR to nick the DNA, activating a gene that produces an alternative form of hemoglobin. To receive the sickle-cell treatment, patients in Britain must be at least 12 years old and have experienced repeated episodes of extreme pain.

There is no upper age limit, nor are patients excluded because they have suffered too much organ damage from sickle-cell disease, said Dr. David Altshuler, Vertexs chief scientific officer.

But the patients must have no other options. Sickle-cell disease can be cured with a bone-marrow transplant, but few patients have compatible donors.

For people struggling with the illness, the Vertex and Bluebird treatments have been a long time coming. Pain is not the only complication people with sickle-cell disease also suffer bone and organ damage and strokes. The misshapen blood cells do not survive long, resulting in anemia.

Still, the CRISPR and Bluebird treatments are onerous and will require expertise that most hospitals lack.

Patients must receive intense chemotherapy to clear their bone marrow of abnormal stem cells and make room for the genetically altered cells. Then the patients must stay a month or more in a hospital while their marrow regrows.

And gene editing is expensive. Vertex and CRISPR Therapeutics have not set a price yet in Britain that will depend on conversations with those who will be paying for it, said Stuart Arbuckle, executive vice president and chief operating officer at Vertex.

The price in the United States, though, is expected to be millions of dollars per patient. Sickle-cell disease itself is expensive, however, costing the U.S. health system an estimated $3 billion a year.

In the United States, Bluebird already has a gene therapy approved for beta thalassemia. It costs $2.8 million per patient.

Dr. Altshuler said Vertex was testing its sickle-cell treatment in children ages 5 to 11, hoping to prevent the irreversible organ damage that occurs over time.

The companys first sickle-cell patient, Victoria Gray, said on Thursday that the treatment changed her life.

Ms. Gray, a Walmart associate in Forest, Miss., was diagnosed with sickle-cell disease when she was 3 months old and had a pain crisis. Those episodes became a part of her life, resulting in frequent hospitalizations.

A lot of my dreams, I couldnt do, she said. The smallest things cold, changing weather I would end up in the hospital.

She had the gene editing treatment in 2019, when she was 33. Now, she said, all her symptoms have vanished.

It meant a new beginning, Ms. Gray said. It is more than I ever dreamed of, for everything to be gone.

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Sickle-Cell Treatment Created With Gene Editing Wins U.K. Approval - The New York Times

Novel Microfluidic Method Optimizes Stem Cell Extraction for … – Technology Networks

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Researchers from the Critical Analytics for Manufacturing Personalized-Medicine (CAMP) Interdisciplinary Research Group (IRG) of Singapore-MIT Alliance for Research and Technology (SMART), MITs research enterprise in Singapore, in collaboration with the Agency for Science, Technology and Research (A*STAR) Bioprocessing Technology Institute (BTI) and National University Health System (NUHS), have developed a groundbreaking technology capable of extracting mesenchymal stem cells (MSCs) directly from pure bone marrow also known as bone marrow aspirate (BMA), a pivotal source of MSCs without dilution.

Using a world-first continuous sorting technique on a multi-chip Deterministic Lateral Displacement (DLD) microfluidic platform, the new method doubles the quantity of MSCs obtained from bone marrow samples and shortens the time taken to around 20 minutes. It also reduces donor discomfort due to less bone marrow being extracted, speeds up cell production, and simplifies cell therapy manufacturing. This advancement represents a significant step toward more accessible and efficient advanced medical treatments that use MSCs including treatment for osteoarthritis, autoimmune and infectious diseases, and neurological disorders.

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Cell therapy is a field of medicine where cells are used as living drugs to fight diseases or restore and replace damaged cells. Advances in regenerative medicine and immunotherapy have benefited countless patients; they offer numerous new treatment alternatives to previously intractable diseases, with hundreds more in the developmental pipeline that gives new hope to patients. However, obtaining high-quality raw materials in this case, MSCs has long been a hurdle in cell therapy manufacturing, as traditional isolation methods such as centrifugation are inefficient and complex. In addition to a long processing time of around two to three hours, current methods result in low yield due to challenges such as osmotic stress and complex workflows. State-of-the-art sorting techniques such as fluorescence-activated cell sorting (FACS) rely on costly antibodies and intricate preparation, posing major limitations for manufacturing of these living medicines.

In a paper titled Scalable mesenchymal stem cell enrichment from bone marrow aspirate using DLD microfluidic sorting, recently published in the journal Lab on a Chip, SMART researchers have pioneered a revolutionary stem cell sorting platform, addressing the challenges of large-scale cell sorting and manufacturing. Using DLD microfluidic technology, a label-free cell sorting method which distinguishes between stem cells and blood cells, the platform processed small bone marrow samples (2.5mL) in just 20 minutes with double the stem cell yield compared to traditional methods, and bypasses costly reagents and complex processes.

In this method pioneered by SMART, human bone marrow samples that arrive at the laboratory undergo a simple filtration step to remove unwanted cells and tissues that could obstruct the chip. Samples are then loaded onto SMARTs sorting platform, and cells of interest (MSCs) are automatically sorted and collected in outlet reservoirs. These collected cells are then combined into a vial for further processing and quantification as needed.

This innovative breakthrough in cell sorting utilises microfluidic technologies, leveraging cells' natural properties and eliminating the necessity for labelling. With conventional methods, cells are sorted using fluorescent or magnetic tags to label certain cellular features. This is challenging as these labels could interfere with subsequent analysis and testing, or worse damage the cells. In comparison, passive techniques like the DLD method developed at SMART are user-friendly, gentle on cells and easily integrated into clinical sample processing workflows. MSCs are very sensitive to its external environment, and perturbations could alter the biology in unanticipated ways.

"This novel platform provides a fresh perspective for stem cell sorting through a more efficient, label-free and, importantly, seamless process integration into current industrial manufacturing pipeline. Our research team at SMART is excited about the possibilities this technology brings to the field of stem cell research and therapy. The successful demonstration of this technology gives us greater confidence to venture into other bioprocessing applications such as leukopheresis with great potential for clinical impact. This will significantly accelerate the development of cutting-edge treatments and improve accessibility for cell therapy," said Mr Nicholas Tan, Research Engineer at SMART CAMP and lead author of the paper.

Even though DLD cell sorting has previously been demonstrated, what is new in this work is that we were able to deploy the technique at a sufficiently high processing flow rate to impact real-world stem cell manufacturing workflow. Biomanufacturing and bioprocessing are areas in which I see much potential for applying microfluidics technology to improve overall efficiency and reduce the cost significantly, said Professor Jongyoon Han, Co-Lead Principal Investigator at SMART CAMP, Professor of Biological Engineering and Electrical Engineering at MIT and corresponding author of the paper.

Future efforts will focus on refining the technology by evaluating the quality of sorted MSCs from human bone marrow samples using methods such as reverse transcription polymerase chain reaction (RT-PCR) and differentiation assays. Simultaneously, CAMP is working towards increasing sorting speed and resolution, while refining the system's design for portability and user-friendliness, and increasing throughput to 10 ml per minute.

Our innovative approach marks a paradigm shift in cell sorting, a key process of cell therapy. By harnessing microfluidic technologies to capitalise on cells' intrinsic properties, we have eliminated the need for cumbersome and expensive labelling methods. It not only streamlines the sorting process but also ensures more accurate and reliable results in medical research. This breakthrough, driven by our commitment to advancing scientific frontiers, heralds a milestone in the realm of cellular studies," said Dr Kerwin Kwek, Research Scientist at SMART CAMP and co-lead author of the paper.

Reference:Tan Kwan Zen N, Zeming KK, Teo KL, et al. Scalable mesenchymal stem cell enrichment from bone marrow aspirate using deterministic lateral displacement (DLD) microfluidic sorting. Lab Chip. 2023;23(19):4313-4323. doi:10.1039/D3LC00379E

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Novel Microfluidic Method Optimizes Stem Cell Extraction for ... - Technology Networks

Priority Health Denied His Last Hope, CAR-T Cancer Treatment – ProPublica

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This story is part of a partnership with Scripps News.

Forrest VanPatten was 50 and strong after years as a molten-iron pourer when he learned in July 2019 that a hyperaggressive form of lymphoma had invaded his body. Chemotherapy failed. Because he was not in remission, a stem cell transplant wasnt an option. But his oncologist offered a lifeline: Dont worry, theres still CAR-T.

The cutting-edge therapy could weaponize VanPattens own cells to beat back his disease. It had extended the lives of hundreds of patients who otherwise had no chance. And VanPatten was a good candidate for treatment, with a fierce drive to stay alive for his wife of 25 years and their grown kids.

VanPatten didnt know it, but he also had the law on his side. His home state of Michigan had long required health insurers to cover clinically proven cancer drugs.

He and his family gripped tight to the hope that the treatment promised.

Then, his insurance company refused to approve it.

Across the country, health insurers are flouting state laws like the one in Michigan, created to guarantee access to critical medical care, ProPublica found. Fed up with insurers saying no too often, state legislators thought theyd solved the problem by passing hundreds of laws spelling out exactly what had to be covered. But companies have continued to dodge bills for pricey treatments, even as industry profits have risen. ProPublica identified dozens of cases in which plans refused to pay for high-stakes treatments or procedures from emergency surgeries to mammograms even though laws require insurers to cover them.

Companies can get away with this because the thinly staffed state agencies that oversee many insurers typically dont open investigations unless patients file complaints. Regulators acknowledge they catch only a fraction of violations. We are missing things, said Sebastian Arduengo, an assistant general counsel for Vermonts insurance department.

Use our free tool to request your records and see why your insurance company turned you down.

Find Out Why Your Health Insurer Denied Your Claim

In the 34 years since Michigan began to require cancer coverage, regulators there have never cited a company for violating the law.

Like most policyholders, VanPatten had no insight into the decision made by his insurer, a nonprofit called Priority Health that covers about a million Michigan residents.

He didnt know that around the time the therapy won the Food and Drug Administrations approval, executives at Priority Health had figured out a way to weasel out of paying for it.

Through interviews with former employees and a review of company emails and VanPattens medical records, ProPublica was able to crack through the usual secrecy and expose the health insurers calculations.

Former employees said the decision not to cover this treatment and a related one was driven almost entirely by their high price tags up to $475,000. Side effects that could land a patient in the hospital can push the bill over $1 million. Priority Health number crunchers calculated to the penny the monthly cost per policyholder if the company shifted the expense to them: 17 cents. But executives didnt raise premiums or absorb the extra cost. They decided to save that money.

Patients needs werent part of the equation, recalled Dr. John Fox, then Priority Healths associate chief medical officer. It was, This is really expensive, how do we stop payment?

Over Foxs objections, fellow executives came up with a semantic workaround: These cancer drugs arent technically drugs, they argued, theyre gene therapies. All Priority Health had to do was to exclude gene therapies from its policies, and it could say no every time.

Priority Health said in a written statement to ProPublica that it provides compassionate, high-quality, affordable coverage and spends 90 cents of every premium dollar on member care.

We are committed to making medical innovations available to members as quickly as possible, regardless of cost, as soon as they have been proven to be safe and effective, Mark Geary, a spokesperson, wrote. The company said it initially didnt cover CAR T-cell therapy because there was a lack of consensus about the treatments effectiveness.

Major life-threatening complications and side effects were common, with a high rate of relapse, the statement said.

At the time of VanPattens denial there was, in fact, already substantial consensus about the medication. In December 2017, the National Comprehensive Cancer Network, then an alliance of 27 leading U.S. cancer treatment centers, spelled out in its guidelines for B-cell lymphomas which patients should receive the therapy and when. VanPattens doctor said he met the criteria.

It was, This is really expensive, how do we stop payment?

VanPattens family signed a privacy waiver giving Priority Health permission to discuss his case with ProPublica. Nevertheless, Priority Health did not respond to questions about his case or whether the company had violated Michigans mandate to cover cancer drugs when it refused to pay for his therapy.

VanPatten was disappointed but tried to remain optimistic after the first denial in January 2020. He and his wife, Betty, who worked in medical billing, knew it often took an appeal to coax the insurer to approve care.

In early February, Dr. Stephanie Williams, then the head of the blood and marrow transplant program for Spectrum Health, came to see VanPatten in his hospital room on Grand Rapids Medical Mile. It had been more than six months since his diagnosis.

He was sitting up in bed hooked up to an IV. His face, once framed by reddish eyebrows and a signature goatee, was hairless and drained of color. Betty pasted on a tight smile.

Priority Health had denied the treatment again, Williams told them, though she vowed to keep fighting.

When she left the room, VanPatten swung his legs over the side of the hospital bed. He had remained resilient and good-humored through his illness. But at that moment, he felt like Priority Health was treating him like an expense, not a person. It got to him, the idea that the insurer he dutifully paid each month knew this was his only chance and was holding it just out of reach.

He grabbed a tissue box from a tray and hurled it against the wall.

Fox, whom Willams described as the conscience of the company, had long been the point person for oncology in Priority Healths medical department. In his earlier life as a practicing physician, he had trained at the Centers for Disease Control and Prevention as a chronic disease epidemiologist. When he joined Priority Health in 2000, he admired the companys focus on preventive care and the fact that his bosses encouraged him to build deep relationships with local hospitals and doctors.

CAR T-cell therapy was a breakthrough more than 20 years in the making, and Fox had tracked clinical trials and talked to oncologists about it. By genetically reengineering patients own white blood cells, then infusing them back into the body to fight cancer, the treatment helped most participants in clinical trials get into remission within three months.

He knew this would be a game changer for patients. He also knew the law. So when news of the FDAs approval of the first CAR-T medication, Kymriah, hit his inbox in August 2017, he recalled, I said, You know, were required to cover this. This is a treatment for cancer.

But the culture at Priority Health had shifted over the previous year under new leadership to focus on cost savings, Fox and four other former employees said in interviews. The company brought in a new chief medical officer, Dr. James Forshee, in late 2016 from Molina Healthcare, an insurer known for wringing profits out of Medicaid managed care plans.

In conversations about the new treatment, several former Priority Health employees recall, Forshee pointed out that the law required covering cancer drugs, and he argued that the new treatment actually wasnt a drug; it was a gene therapy. (Through a company spokesperson, Forshee declined to comment for this article.)

Fox thought this was ridiculous. He pressed company lawyers for an opinion. Priority Healths filings with the state indicate that we have to cover FDA approved cancer drugs, Fox wrote to two members of the legal department in a September 2017 email.

Senior counsel John Samalik responded, bolstering Forshees position that Priority Health didnt have to cover Kymriah: I believe legally we have a defensible argument that Kymriah is a gene therapy and not a drug. (Samalik declined to comment through a company spokesperson.)

Fox pointed out that the company already covered another gene therapy. He told ProPublica that he suggested asking state regulators whether the cancer-drug mandate applied to Kymriah, but Forshee and at least one other executive refused.

My inference being that, if we ask the state, they would say yes, so lets not ask, Fox said. Two other former Priority Health employees involved in the discussions confirmed Foxs recollections.

The FDA approved a second CAR T-cell medication, Yescarta, seven weeks after the first approval.

When ProPublica asked if the FDA considered CAR T-cell therapies drugs, an agency spokesperson said yes. She wrote in an email that they have been regulated as gene therapies, and that they are biological products and drugs under the Public Health Service Act (PHS Act) and the Federal Food, Drug and Cosmetic Act.

Fox continued to push Priority Health to cover them; Forshee didnt budge.

As they often did for new therapies, Priority Healths actuaries calculated the price tag. They estimated that each year, one patient would need Yescarta and one Kymriah. If spread across the companys members, the therapies would cost an extra 17 cents per member per month 8 cents for Yescarta and 9 cents for Kymriah, emails show.

If the company had chosen to absorb the cost rather than raise premiums, the extra expense potentially more than $1 million for each patient receiving the therapy could have hurt its bottom line. Other insurers had also balked at the cost of CAR-T and were slow to cover it.

Priority Health made a slight tweak to its 2018 filings to state regulators, one with life-changing implications for patients like VanPatten. As it had in the past, the company said it covered drugs for cancer therapy as required by state law. But the insurer slipped in a new sentence more than a dozen pages later: Gene therapy was not a Covered Service.

Watch the Scripps News Report Hope Denied

Meanwhile, regional and national health plans began approving the drugs. Kaiser Permanente started covering them within months of the FDAs approvals. Blue Cross Blue Shield of Michigan the states biggest health plan and Priority Healths main competitor paid for a cancer patient to receive CAR T-cell therapy in December 2017. (A spokesperson said in an email that the plan added coverage based on the treatments efficacy, without considering whether Michigans mandate applied. We would have covered these drugs irrespective of the law, she said.)

When the national Blue Cross Blue Shield Association made an announcement about CAR-T coverage later in 2018, employees at Priority Health forwarded it to one another. It was an I-told-you-so moment for Fox.

At a meeting that December, Fox made the case again that Priority Health should ask the state whether Michigans law required covering the new cancer treatments.

Forshee bristled. You dont trust our legal counsel? he responded, according to Fox and another executive who attended.

His own temper rising, Fox considered what would happen if the company maintained its position. Patients who needed these therapies would likely die. Fox and his team would have to sign the denial letters, knowing the despair and anger they would sow.

After working at Priority Health for more than 18 years, Fox had once thought hed retire there. He left that meeting certain he had to move on.

Health plans have a right to make money; were providing a service, Fox said. But we have to do that honestly and fairly, putting patients first, not profits or premiums first. To me, thats where we crossed the line.

About seven months later, on a sticky night in July 2019, Forrest and Betty VanPatten were sipping beers with friends at the local club of the Fraternal Order of Eagles.

When theyd moved to Sparta, a small Michigan town known for its apple orchards, this was where theyd found community. The club had hosted countless charity raffles and fundraisers, including a pink night for the American Cancer Society for which Forrest squeezed into a hot-pink minidress Betty sewed for him. (There wasnt much off-the-rack that could fit his almost 6-foot-8-inch frame.)

They were expecting biopsy results at any moment. Forrest had gone to the emergency room the previous weekend with intense pain. Hed made it through two previous bouts of lymphoma and suspected he was about to face another.

Forrests phone rang. It was the office of his primary oncologist, Dr. Brett Brinker. Oncologists meet hundreds of patients and their families, but Brinker had grown deeply fond of the VanPattens. Forrest was the guy who could talk to anyone, who made the party worth attending. Betty was his perfect foil. Their laughter and candor left a lasting impression.

The news was bad. Forrest had something called Richters transformation. It made his lymphoma significantly more aggressive and less likely to respond to conventional chemotherapy. After hanging up, Forrest typed Richters into his phone. Almost immediately, he proclaimed, This is a death sentence.

Betty needed to clear her head. She walked around the block, passing a restaurant where Forrests name was on the wall for completing a taco-eating challenge. When she got back, she urged Forrest to snap out of his defeatism.

He had just celebrated his 50th birthday and was determined to be around for his 51st. His kids, Donovan, 23, and Madison, 22, were in serious relationships, and he wanted to be there for their weddings.

So we went in and got a game plan, Betty said. Forrest would begin with chemotherapy, and, if the cancer went into remission, they would try for a stem cell transplant. If the cancer didnt go into remission, Brinker made it clear they werent out of options. He told them about CAR-T.

It felt reassuring at the time.

By January 2020, CAR-T was all they had left. Brinker said he thought the treatment could at least bring Forrests disease under control for a few years. Its hard to use the word cure when its acting like that, he said of Forrests cancer. But if they won some extra time, he said, theres always something in the wings you can hope for.

On Jan. 28, Williams, the doctor who ran the transplant program, worked with her team to submit a request for coverage to Priority Health. Williams knew the companys policy on CAR-T but thought the insurer might relent when faced with an actual patient who was certain to die without the treatment. Plus, by that point, the federal government was covering the therapies for Medicare patients, and insurers often follow its lead.

Knowing it could take weeks to grow the cells used in the treatment, his doctors prepared to extract his white blood cells. These are diseases where we dont have a lot of time to waste, Williams said.

Then Williams office found out that Priority Health had denied the request. Forrests doctors appealed but were turned down again, prompting Forrest to throw the tissue box at the wall.

Williams felt it, too. I was deflated. I was angry, she recalled. We kept trying to work it out, and we kept hitting roadblocks.

The VanPattens didnt have the money to pay out of pocket, and Forrest didnt want to saddle his family with medical debt. His medical team filed a third and final appeal, this one to an independent reviewer.

As that went forward, the VanPattens received a letter from Priority Health explaining its reasons for denying Forrests treatment. CAR-T cell therapy is not a covered benefit, and therefore, we are unable to approve this request, the letter stated. Somehow, seeing the words in writing conveyed a different finality, sending Forrest into a downward spiral.

Everybody deserves the chance of fighting, Betty said. Once you take somebodys hope away, you kill them you really, really do. It was evident with him. He was defeated, and he had never been defeated in his life, and that was hard to watch.

He was defeated, and he had never been defeated in his life, and that was hard to watch.

Their son, Donovan, took to social media to blast Priority Health for its decision, hoping to shame the company into a last-minute about-face. He included a screenshot of a text message from Forrest, who knew his insurer was an outlier. It should be noted that Blue Cross and Blue Shield of MI pays for Car T Cell! it read.

A reporter for Scripps News Grand Rapids, WXMI, a local TV news station, interviewed Forrest on Feb. 13 in the suede recliner hed long claimed as his chair in the familys living room.

I feel like Im being ignored, he said, tears streaming down his face. Left out to die, basically.

Days later, Forrest was back in Butterworth Hospital with shortness of breath. He is in acute distress, an emergency room doctor noted when he was admitted.

The following night, his heart stopped beating. Betty retreated to the back of the room as doctors and nurses swarmed in. Donovan sat in a chair outside, his head in his hands.

Madison raced through Grand Rapids snow-covered streets to join them. When she reached her fathers room, a member of the medical team was still pushing down on his chest. But, she recalled, it was clear he wasnt there anymore. The family told his doctors to end the resuscitation effort.

Forrest died on Feb. 17, before the independent medical reviewer had a chance to weigh in. Three weeks had passed since Williams and her team had asked Priority Health to cover the therapy.

Williams said that if Priority Health had approved the first request, Forrest could have received the infusion. Its unknowable whether the treatment would have given him more time, she said, but if hed had that chance, anything is possible.

Not long after Forrest died, his family received a handwritten card from a clinical coordinator who cared for him.

I am so so so sad that we didnt get the chance to put the rest of our plan into motion, she wrote. In honor of your kind (+very funny) husband, dad, friend, I promise to continue to push for Priority Health to cover CAR-T and to bring hope to all who need it.

In Priority Healths statement, Geary, the spokesperson, wrote that the company began covering the therapy after extensive clinical work improved the treatment. The company would not say when it began paying for the treatment or whether Forrests death influenced its decision.

It is devastating when a disease takes a members life, the statement said. We recognize the deep pain of losing someone you love.

To former state Sen. Joe Schwarz, now 86 and retired, the story of Priority Health and Forrest VanPatten is a painful echo of a problem he thought hed fixed.

More than 30 years ago, Schwarz helped write the Michigan law requiring insurers to pay for cancer drugs. Schwarz, a physician, still recalls what drove him to action: Insurance companies were refusing to pay for drugs given to make chemotherapy more effective, arguing they werent themselves chemotherapy. An op-ed in the Wall Street Journal by the head of the Association of Community Cancer Centers confirmed that insurers nationwide were denying coverage for cancer patients.

At a Senate hearing, Schwarz accused health plans of abandoning their policyholders based on a play on words. When ProPublica told Schwarz about Priority Healths gene-therapy argument, he let out a mirthless hah, scoffing at the wordplay.

You shouldnt split hairs between the term gene therapy and the term chemotherapy or the term radiation therapy or the term surgical therapy, he said. Theyre all cancer therapies and they should all be covered.

You shouldnt split hairs between the term gene therapy and the term chemotherapy or the term radiation therapy or the term surgical therapy. Theyre all cancer therapies and they should all be covered.

ProPublica gave Michigans Department of Insurance and Financial Services a detailed description of VanPattens case, as well as Priority Healths contention that it didnt have to cover CAR T-cell cancer therapies. We asked if Priority Health broke the state law on cancer treatments. Laura Hall, the departments communications director, wouldnt say. The agency can investigate if it spots a pattern of improper denials, but in general, she said, it only acts if a patient or their representative files a complaint.

The VanPattens didnt do that. And they didnt know about the Michigan law until ProPublica told them about it.

In the months after her husband died, Betty VanPatten was too weighed down by grief and anger to tangle with Priority Health through state insurance regulators. The days were a blur. Donovan and his partner, McKenzie, moved in with Betty, who threw herself into her job.

Id get up at 4, and Id have my laptop and I just worked until about 9 or 10 oclock, Betty said. And a lot of times Id just sit there and the tears are just running down my face.

The VanPattens still struggle with the sense that Forrest suffered an injustice and that Priority Health got away with it.

They lost sight of the patient, Betty said at a family dinner this July. Madison agreed.

Insurance is meant to protect people, she said, not to make them fight through the last day to get what they should.

Do You Have Insights Into Dental and Health Insurance Denials? Help Us Report on the System.

Insurers deny tens of millions of claims every year. ProPublica is investigating why claims are denied, what the consequences are for patients and how the appeal process really works.

Kirsten Berg contributed research.

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Priority Health Denied His Last Hope, CAR-T Cancer Treatment - ProPublica

Vor shares new data for stem cell therapy; Melinta partners with … – Endpoints News

Plus, news about BeiGene, Zymeworks, Rznomics, and Adicet:

Vor Bio shares early data for its gene-edited stem cell therapy: The company announced Thursday that its stem cell treatment seemed to engraft normally in seven patients with acute myeloid leukemia (AML) treated so far. Three patients who received Mylotarg Pfizers AML drug saw protection from deep cytopenias, or a steep drop in blood cell counts thats often seen as a side effect of the drug. Mylotarg targets CD33, an antigen found in high levels on leukemia cells but also expressed in some normal cells. Vor, founded on research led by Siddhartha Mukherjee, edits CD33 out of donor stem cells with the goal of sparing patients from the treatments side effects. More data are set to be presented at ASH, the company announced last week. Lei Lei Wu

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Vor shares new data for stem cell therapy; Melinta partners with ... - Endpoints News