Bluebird set for Lyfgenia’s launch after ‘remarkable’ approvals

FDA cleared SCD gene therapies Lyfgenia, Casgevy on Dec. 8

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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On Dec. 8, the U.S. Food and Drug Administration (FDA) approved two cell-based gene therapies for sickle cell disease (SCD), a groundbreaking decision that now offers patients more than one potentially curative option that targets the underlying cause of the disease.

Bluebird Bio’s Lyfgenia (lovotibeglogene autotemcel) — formerly lovo-cel — was cleared for SCD patients, ages 12 and older, with a history of vaso-occlusive events (VOEs). It was approved along with Casgevy (exagamglogene autotemcel), or exa-cel, from Vertex Pharmaceuticals and CRISPR Therapeutics.

“To have two transformative therapies approved for this community, after nearly a century of underinvestment, is truly remarkable,” Bluebird Bio told Sickle Cell Disease News in a written Q&A. “A one-time therapy like Lyfgenia that addresses the underlying cause of sickle cell disease has the potential to not only deliver transformational improvements in health and quality of life, but also reduce the lifetime economic and societal burden of disease by lowering health care utilization and allowing patients to pursue their life and career goals.”

Lyfgenia is set for a commercial launch in early 2024. It will only be available through a national network of qualified treatment centers that have the necessary expertise for the procedure.

Bluebird is offering my bluebird support, a free patient services program, that will provide patients and their families personalized support throughout the treatment process, including guidance on insurance coverage and financial assistance options.

The list price for Lyfgenia is set at $3.1 million, joining other gene therapies as among the most expensive treatments worldwide. Casgevy will cost $2.2 million.

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How will Lyfgenia be paid for?

Bluebird said the price was set “in recognition of the potential lifetime impact that reducing or eliminating pain crises may have on healthcare utilization, future earnings, and life opportunities.”

The lifetime costs of SCD over a median lifespan of 45 years are estimated to be about $4 to $6 million. This total doesn’t include other out-of-pocket costs to patients and caregivers,  according to the company.

“People living with sickle cell disease forego an estimated $1.3M in lifetime earnings based on how their disease impacts academic and professional opportunities,” Bluebird noted.

By preventing the symptoms that lead to these high long-term costs, Lyfgenia’s developer believes the therapy has a high value for its price. The company is also confident in their approach to ensure insurance companies or other payers will cover it.

“Our philosophy is simple: set a value-based price and offer a contracting approach that puts our money where our mouth is,” the company wrote.

Essentially, this means an outcomes-based agreement with payers, wherein the therapy is only covered if it leads to certain clinical benefits to the patient, thereby tying the cost of Lyfgenia to its performance.

“We can stand behind our therapies in this way because our data show transformative benefits sustained through five years — something no one else in the field can say,” the company said.

Bluebird has already entered into such an agreement with a large organization that covers 100 million Americans, “underscoring that payers recognize the value of Lyfgenia and are ready to support access,” it noted. Discussions are underway to ensure coverage under Medicaid, a federally run health insurance program for lower-income Americans.

How Lyfgenia works on SCD

In SCD, an abnormal form of hemoglobin, the protein responsible for carrying oxygen in red blood cells, is produced due to mutations in the HBB gene. This deforms red blood cells, causing them to take on a sickle-like shape that makes it difficult for them to pass through blood vessels.

It also increases the risk of vaso-occlusion, or blood flow blockage, which can restrict oxygen transport to certain parts of the body. This leads to painful vaso-occlusive crises (VOCs), acute chest syndrome, and other sickle cell-related complications, collectively known as VOEs.

Lyfgenia provides patients with a version of the HBB gene that encodes HbAT87Q, a form of hemoglobin with strong anti-sickling properties. The genetic material is packaged into a lentivirus carrier and inserted into a patient’s own hematopoietic stem cells, or blood cell precursors, in the lab.

When the modified cells are infused back into the patient via a stem cell transplant, they should populate the body with red blood cells capable of producing healthy hemoglobin, thereby preventing red blood cell sickling and VOEs. A patient must undergo a round of chemotherapy ahead of the transplant to eliminate faulty blood cells.

Fifty-nine patients have been treated with Lyfgenia across multiple clinical trials ands some have been followed for more than eight years. These data make Lyfgenia the “most deeply studied gene therapy” for SCD, Bluebird said.

Efficacy data backing Lyfgenia’s approval in the U.S. largely came from the open-label Phase 1/2 HGB-206 clinical trial (NCT02140554), which tested it on adults and adolescents with severe SCD. An ongoing Phase 3 trial called HGB-210 (NCT04293185) is designed similarly, but is recruiting patients in the U.S. as young as 2.

At a recent scientific conference, the company presented efficacy data from 34 patients who received the gene therapy in either trial. They’d been followed for a median of about three years and some have been monitored for more than five years since being treated.

Results showed 88.2% of the patients were free from VOEs throughout follow-up, and 94% were free from severe VOEs, or those that required hospitalizations, visits to urgent care, or into-the-vein (intravenous) treatment. All 10 adolescents who were evaluated were entirely free of VOEs.

For the eight people who did have a documented VOE during the trial, the rate decreased by at least 50% compared with the period before gene therapy, and the median time spent in the hospital decreased from more than two weeks a year before treatment to around two days a year after it.

Most patients also reported meaningful improvements in quality of life, “giving us confidence that this therapy is making a difference,” Bluebird said.

Production of anti-sickling hemoglobin increased and remained stable during follow-up.

“Results in the efficacy cohort have been sustained through [five] years of long-term follow-up — the most of any gene therapy in the field — giving confidence that this transformational impact can be sustained over time,” the company said.

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An ongoing study called LTF-307 (NCT04628585) is monitoring Lyfgenia’s long-term safety and efficacy in patients who participated in earlier clinical trials, for a total of 15 years. The study will help establish whether the effects of the one-time gene therapy are durable beyond the scope of the initial clinical trials.

Still, Bluebird said the therapy is not intended for re-dosing, noting, “the goal … is to treat a patient once to enable lifelong benefits.”

Regarding its safety profile, “Lyfgenia is extremely well characterized and well understood by clinicians,” the company stated. The most common side effects include inflamed and sore mouth (stomatitis) and low blood cell counts.

The therapy’s prescribing information comes with a boxed warning of the risk for hematologic malignancy, or blood cancer. Two patients who received earlier versions of the gene therapy developed leukemia, a type of blood cancer, after treatment.

Bluebird said it’s since made “industry-leading/industry-defining changes … to [the] treatment process,” and said the boxed warning on the FDA label serves as “a tool for transparency for a community where trust is critical Our research continues to show that clinicians favor Lyfgenia given the unmatched follow up and the transparency with which we have published data.”

Bluebird believes the dual approval of Lyfgenia and Casgevy represents a “remarkable moment for the sickle cell disease community,” and is “extremely proud to be part of” that. “For patients, two gene therapies come after nearly a century of waiting; for bluebird and the field at large, this milestone marks the culmination of a 10-year scientific odyssey.”