By Jack Rawson, Analyst
October 2018 turned out to be a good month for β-thalassemia patients seeking new and effective treatments. The European Medicine Agency (EMA) accepted US-based biotech firm bluebird bio’s marketing authorization application (MAA). The new gene therapy – LentiGlobin – could be a gamechanger for patients with transfusion-dependent β-thalassemia (TDT).
As the name suggests, this form of the disease is dependent on periodic blood transfusions. Untreated TDT progresses with severe anaemia, splenomegaly, bone deformities and death before the age of 20. EMA have begun to undertake an accelerated review of this blood disorder therapy 1,2.
The acceptance came after LentiGlobin was granted `Accelerated Assessment’ by the Committee for Medicinal Products for Human Use (CMPHU) in July 20183. This decision was made based on clinical data from a Phase 1/2 Northstar (HGB-204), Phase 1/2 (HGB-205) study, and Phase 3 Northstar-2 (HGB-207) study (NCT02906202, NCT02151526, NCT01745120)4. The FDA had previously assigned orphan drug status and breakthrough therapy designation to this drug5.
The LentiGlobin gene therapy works by inserting a functional β-globin into the patient’s own hematopeietic stem cells, ex vivo. These cells are then transplanted into the patient bloodstream5,6.
Current treatments in the area have significant unmet need. Patients receiving the monthly transfusions also require iron chelation which causes approximately 3,000 deaths annually due to iron overload. Progressive accumulation of iron in the body leads to tissue damage, and eventually death from cardiac disease.
Together transfusion and chelation therapy costs are at an estimated £480,000 over a patient’s life. 71% of β-thalassemia major patients die from cardiac complications. A UK based study showed expected probability of survival at 50 years to be 63%, with only 33% of these expected to be without any complications.
Bone marrow transplants are an alternative option. However, this comes with its own set of problems- namely finding donors, the associated risks and costs. Allogeneic bone marrow transplants in the UK cost the NHS between £300,000 and £750,00013.
Figure 1: Types of therapies available for TDT with cost estimates
|Type of Therapy||Cost Estimates (£)|
|Transfusion and Chelation Therapy12||£480,000*|
|Allogenic Bone Marrow Transplant||£300,000-£750,000|
|Gene Therapy (US/EU conservative forecast)14||£420,000|
|Gene Therapy (Rest of world conservative forecast)14||£150,000|
*Transfusion and chelation therapy based on 2013/14 estimates with costs including all aspects of therapy including blood transfusions, chelation therapy, lab tests, as well as referrals and physician fees.
A potentially curative treatment for TDT would mean significant improvement over current available options. Despite LentiGlobin’s regulatory success, not all patients were freed of transfusions. Only 7 out of 8 patients involved in bluebird bio’s phase 1/2 study are transfusion free and producing normal levels of haemoglobin (CTID). Even so, these are promising results.
The thalassemia market is attractive. It is growing and is expected to be valued at $3.53 billion by 20227, with a CAGR of 10.8%. TDT is the most common of the β thalassemias. Emerging countries like Thailand offer lucrative opportunities due to relative prevalence of genetic carriers. Despite this, the US is expected to be the fastest growing region due to both prevalence figure and a well-established healthcare system that could ensure access.
A TDT therapy is one of the first examples where a gene therapy could be applied to a large population of patients in developing countries. bluebird bio’s clinical development plan includes sites in Australia, Germany, Greece, France, Italy, Thailand, the UK and the US4.
There are several companies operating in the cell therapy and bone marrow transplant area. These players are likely to utilise their expertise in rare blood diseases including thalassaemia. These include Incyte Corporation, Kiadis Pharma, and Gamida Cell. One to watch is Acceleron Pharma/Celgene’s luspatercept, a first in class red blood cell maturation agent, expected to be launch ready in late 2019.
Future Perspectives in Gene and Cell Therapy
When discussing the technical issues of potential gene therapies, the issue of pricing and reimbursement models are never far behind. At the January 2018 JP Morgan Healthcare Conference, bluebird bio’s chief executive officer, Nick Leschly brought up the issue of healthcare funding and reimbursement. He suggested Medicaid Best Price regulations were a problem. He picked on the mismatch between upfront payment and long-term value, and its impact in recognizing the value of gene therapy.
Future innovation in cell and gene therapy will be dependent on recognizing their value as both costly and revolutionary advancements in medicine. Market access, pricing, and reimbursement are therefore crucial considerations for all players in this market.
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