Regulating therapies for rare diseases – recent approvals

Recommending an innovative gene therapy for NHS use

CASGEVY (exagamglogene autotemcel ‘exa-cel’) is the first gene therapy available in Europe for treating severe beta-thalassaemia. The therapy was granted conditional EU approval in February for severe sickle cell disease characterised by recurrent vaso-occlusive crises or transfusion-dependent beta thalassemia.

Now, the novel gene editing therapy is set to be available for up to 460 eligible NHS patients with beta thalassemia, according to National Institute for Health and Care Excellence (NICE).

In final draft guidance, the regulatory body recommend the therapy for individuals 12 years and older with severe beta-thalassaemia. The indication is for those requiring regular blood transfusions and in cases where a blood and bone marrow transplant is suitable but there is no donor availability. 

Research from GlobalData, published in April, found that deal worth for innovator drugs incorporating clustered regularly interspaced short palindromic repeats (CRISPR)-based technology for various diseases witnessed a “remarkable surge”, with a total deal value of $21 billion from 2020 to 2022. Specifically, the total deal value for haematological diseases surged to $1.8 billion, the research found.

“Innovator drugs harnessing CRISPR technologies saw 182 percent growth in total licensing agreement deal value from $5.6 billion in 2020 to $15.8 billion in 2022,” Ophelia Chan, Business Fundamentals Analyst at GlobalData explained.

Evidence of efficacy for the rare disease

As for clinical evidence, in “November 2023, it was reported that of 42 patients in a trial long enough for early analysis over 90 percent didn’t require a red blood cell transfusion for at least 12 months after treatment, the others needing fewer,” Laurence Hurst, Professor of Evolutionary Genetics at The Milner Centre for Evolution, University of Bath shared.

While the innovative The CRISPR therapy holds promise for patients, at a list price of £1,651,000 per course, it remains to be seen whether the treatment will be cost-effective once it has approval and is available to these individuals.

Secondly, while “there are some uncertainties in the evidence for its long-term benefits, the committee felt exa-cel could represent a potential cure for some people with transfusion-dependent beta-thalassaemia, freeing them from the burden and risks of needing regular blood transfusions,” Helen Knight, Director of Medicines evaluation at NICE stated.

Ultimately, NICE’s decision initiates “a new era of cell and gene therapies in the UK [as it] offers an effective cure for transfusion-dependent beta thalassaemia for people without a stem cell donor,” Dr Diana Hernandez, Director of immune and advanced therapies at stem cell charity Anthony Nolan commented. 

Furthermore, considering CASGEVY’s potential for beta-thalassaemia, “we hope this approval… demonstrates a solution is possible, and urge NICE and Vertex to work together to deliver this treatment to patients with sickle cell as soon as possible,” Yasmin Sheikh, Head of Policy and Public Affairs at stem cell charity Anthony Nolan stated.

EU approval of a novel enzyme replacement therapy

Recently, Takeda shared that its enzyme replacement therapy ADZYNMA^®▼ (recombinant ADAMTS13) was approved in the EU to treat ADAMTS13 deficiency in individuals with congenital thrombotic thrombocytopenic purpura (cTTP).

Therefore, ADZYNMA is the first enzyme replacement therapy in the EU for the treatment of this ultra-rare, chronic blood clotting disorder. It is the first recombinant “A disintegrin and metalloproteinase with thrombospondin motifs 13” (ADAMTS13) enzyme replacement therapy.

Authorisation by the European Commission was supported by evidence from an interim analysis of a Phase III trial, of which findings were published in The New England Journal of Medicine in May 2024.

“This approval marks the first treatment specifically indicated to address the root cause of the disease – ADAMTS13 deficiency,” explained Ricardo Marek, President, Europe and Canada Business Unit at Takeda.

Expanding treatment options for rare kidney disease

This week, Novartis achieved a novel approval for its first-in-class complement inhibitor for the kidney disorder primary immunoglobulin A nephropathy (IgAN).

Accelerated approval for Fabhalta^® (iptacopan) was authorised by the US Food and Drug Administration (FDA).

The treatment is indicated for reducing proteinuria in adults with primary immunoglobulin A nephropathy (IgAN), who are at risk of the disease progressing quickly.

This follows a promising data release by the company in April, for Fabhalta as a therapy to treat IgA nephropathy.

The FDA’s decision is based on an interim analysis of the ongoing Phase III APPLAUSE-IgAN trial, which demonstrated that Fabhalta enabled a 38 percent proteinuria reduction versus placebo.

“Mounting clinical evidence underscores the pivotal role of complement activation in IgA nephropathy. I am thrilled that this advancement is now available to help enable a targeted treatment approach for IgAN patients,” remarked Professor Dana Rizk, Investigator and APPLAUSE-IgAN Steering Committee Member and professor in the University of Alabama at Birmingham Division of Nephrology.

“Approval of Fabhalta as a first-in-class medicine for IgA nephropathy is an important milestone in our journey to evolve rare renal disease care by bringing new treatments to people in urgent need of options,” stated Victor Bultó, President US, Novartis. The company noted that Fabhalta (iptacopan) is the first treatment in its renal pipeline to be given approval by the FDA.