May 19, 2024

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Two gene therapies for sickle cell disease priced at $1.35 million to $2.05 million


Two gene therapies for sickle cell disease priced at $1.35 million to $2.05 million.


While gene therapy brings potential cures to patients, it often comes with a high price tag. But for the promise of individualized treatment for sickle cell disease (SCD), at least as far as ICER is concerned, the cost may be worth it.

The Institute for Clinical and Economic Review (ICER), which has performed customary cost-benefit calculations, has published a revised evidence report evaluating the clinical efficacy and value of two gene therapies for SCD: exagamglogene autotemcel (exa-cel) from Vertex Pharmaceuticals and CRISPR Therapeutics and lovotibeglogene autotemcel (lovo-c el).


Two gene therapies for sickle cell disease priced at $1.35 million to $2.05 million



Overall, the two gene therapies — both on track for FDA approval in the second half of this year — would meet the cost-effectiveness threshold if priced between $1.35 million and $2.05 million, ICER said last week. None of Bluebird, Vertex, and CRISPR have announced potential U.S. prices for their drugs if they are approved. 


Next, ICER will present its evidence report at a public meeting of the regulator’s Independent Review Committee, which will hear further testimony from stakeholders to consider the drug’s comparative clinical efficacy, other potential benefits, and long-term economic value.


Looking back through the layers of ICER’s review, the organization determined that in SCD, Bluebird’s lovo-cel provided at least an “incremental” net benefit compared with standard care, while the gene therapy prospect may offer a “substantial net health benefit.”


As for Vertex and CRISPR’s exa-cel, the candidate gene therapy is “likely to be comparable to Bluebird” and “likely to produce an incremental net benefit, or a significant net benefit, when evaluated compared to standard care.”


ICER was quick to warn of “important uncertainties” about the long-term safety and efficacy of gene therapy, especially excel-cel, the first CRISPR therapy to file for FDA approval.


“These therapies require autologous bone marrow transplantation, which means they carry important potential risks,” ICER’s chief medical officer Dr. David Rind said in a statement, adding that “the first CRISPR therapy necessarily carries greater long-term risks and uncertainties of lasting benefit than lentiviral gene therapy.”


Bluebird’s application for sickle cell gene therapy lovo-cel was on the FDA’s desk in late April, just shy of its first-quarter 2023 goal. Under priority review, the FDA will make a decision within 6 months.


The filing followed a partial FDA delay on the drug in 2021 when an adolescent patient developed persistent, non-transfusion-dependent anemia after receiving lovo-cel.


Bluebird’s application is just a few weeks behind Vertex and CRISPR, which entered the regulatory review process on April 3.


In a note to clients earlier this year, analyst William Blair wrote that Vertex and CRISPR’s potential lead won’t be as long as initially expected because of the closeness of the filing. The FDA could hold joint advisory committee meetings on the two applications, they added.


If lovo-cel wins regulatory approval, it would be Bluebird’s third approved gene therapy, following beta thalassemia drug Zynteglo and cerebral adrenoleukodystrophy drug Skysona. Bluebird has priced its gene therapy at $2.8 million and $3 million in the U.S., respectively.




About sickle cell disease and its research progress


Sickle cell disease is a genetic disease that mainly occurs in Africa, the Middle East, the Mediterranean and other regions, and a small number of people are also affected in Asia and the Americas.

The main pathophysiological feature of the disease is the mutation of the hemoglobin molecule, which leads to the sickling of red blood cells, which causes a series of clinical symptoms and complications.


The clinical manifestations of sickle cell disease include anemia, jaundice, vascular obstruction, pain crisis, etc., and may lead to organ damage, infection and death in severe cases. In addition, the disease can affect the patient’s quality of life and longevity.


Treatment for sickle cell disease includes measures to relieve symptoms, prevent complications, and gene therapy.

At present, the only way to cure the disease is hematopoietic stem cell transplantation, but due to the difficulty and high cost of transplantation, this method is only suitable for some patients.

Therefore, the treatment of sickle cell disease mainly focuses on the treatment of symptoms and complications, such as blood transfusion and the use of specific drugs for sickle cell disease.

In recent years, gene therapy has gradually attracted attention as a new treatment method, and research on gene therapy for sickle cell disease is also progressing.


Gene repair is to repair the mutation of the sickle cell disease gene by using technologies such as CRISPR/Cas9 to introduce normal gene sequences into the patient’s cells.

The current research shows that this method has achieved certain effects in vitro experiments, but there are still technical difficulties and safety issues in the in vivo application.


In general, gene therapy, as a new type of treatment, has certain potential for the treatment of sickle cell disease. However, for different gene therapies, there are still technical difficulties and safety issues, which need further research and verification.






Exa-cel is an autologous ex vivo CRISPR/Cas9 gene editing therapy under development, intended as a one-time therapy for SCD and TDT.

The therapy works by engineering the patient’s hematopoietic stem cells to produce high levels of fetal hemoglobin (HbF) in red blood cells, thereby alleviating the need for blood transfusions in TDT patients and alleviating the pain and sickle cell crisis in SCD patients.


Exa-cel is the fastest-advancing gene editing method for the treatment of SCD and TDT , and the first CRISPR/Cas9 therapy to prove concept in the clinic.

Existing clinical trial data have shown that patients with severe SCD who received a single infusion of exa-cel quickly achieved robust, sustained, high levels of pan-cellular HbF expression, while reducing pain and sickle crisis.

At the same time, TDT patients who received a single infusion of exa-cel also rapidly achieved robust, persistent, high pan-cellular HbF expression, thereby alleviating the need for blood transfusions.


It is worth mentioning that in February 2023 , the marketing application of Exa-cel for the treatment of SCD and β-thalassemia was accepted by the European Medicines Agency ( EMA ).

Therefore, Exa-cel is expected to become the first CRISPR gene editing therapy approved for marketing . 





lovo-cel is a one-time gene therapy for the treatment of SCD in which hematopoietic stem cells transduced with the BB305 lentiviral vector encoding the engineered β-globin gene (βA-T87Q) are transplanted back into the same patient.

Once patients have the βA-T87Q globin gene, their red blood cells can produce anti-sickle hemoglobin (HbAT87Q), which reduces the proportion of HbS, with the goal of reducing sickling, hemolysis, and other complications.


If it goes well, lovo-cel will become the third gene therapy approved by Bluebird Bio.

Bluebird Bio ‘s first gene therapy is ZYNTEGLO® ( Betibelogene autotemcel , Beti-cel ), which was approved in August 2022 for the treatment of beta – thalassemia with a price tag of $ 2.8 million.

The second gene therapy, SKYSONA® ( Elivaldogene autotemcel , Eli-cel ), was approved in September 2022 to slow the progression of neurological deficits in boys 4-17 years of age with early active cerebral adrenoleukodystrophy ( CALD ) for $ 3 million.





Source: FiercePharma

(source:internet/BT0cUF4Bme9666S3oeTppA, reference only)

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Important Note: The information provided is for informational purposes only and should not be considered as medical advice.