Breakthrough Clinical Results
Quell Therapeutics announced that AstraZeneca has exercised its option to license a lead Treg cell therapy candidate from their joint Inflammatory Bowel Disease (IBD) research program. This milestone triggers a $10 million payment to Quell. AstraZeneca will now lead further development and clinical trials, with Quell providing manufacturing support. This is the second milestone achieved under their 2023 collaboration agreement, following a similar achievement in the Type 1 Diabetes program. Quell is also advancing its own internal clinical program, QEL-001, for liver transplant patients.
Key Highlights
- AstraZeneca licensed a lead Treg cell therapy candidate for IBD from Quell Therapeutics.
- A $10 million milestone payment was triggered.
- AstraZeneca will lead further development and clinical trials.
- Quell will provide CMC support and GMP drug product for a first-in-human trial.
Incidence and Prevalence
Global IBD Burden (2021):
- New Cases: 375,140
- Total Cases: 3.83 million
Trends:
- Incidence Rate Increase: Observed in 167 countries.
- Female Incidence: Increasing (Annual Percentage Change: +0.06%).
- Elderly Incidence: Increasing (Annual Percentage Change: +0.14%).
- Male and Overall Population Incidence: Stable.
Global IBD Burden (2019):
- Total Cases: 4.9 million (95% Uncertainty Interval [UI] 4.3-5.5)
- Age-Standardized Prevalence Rate Decrease (1990-2019): From 73.23 (95% UI 63.8-83.6) to 59.2 (95% UI 52.7-66.4) per 100,000 population.
- Age-Standardized Incidence Rate Decrease (1990-2019): From 6.1 (95% UI 5.3-6.9) to 4.9 (95% UI 4.4-5.6) per 100,000 population.
Regional Variations (2019):
- Highest Prevalence and Incidence: North America.
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Lowest Prevalence and Incidence: Oceania.
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Oceania Prevalence: 209.5 (95% UI 195.4-224.4) per 100,000 population.
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Oceania Incidence: 24.5 (95% UI 22.6-26.7) per 100,000 population.
- High Socio-Demographic Index (SDI) Locations: Highest prevalence, but declining from 1990.
- Middle, Low-Middle, and Low SDI Quintiles: Increasing prevalence and incidence over three decades.
Other Trends (1990-2019):
- Age-Standardized Rates for Deaths, DALYs, YLD, and YLL: Decreased globally.
Note: While the 2021 data provides the most recent incidence numbers, the 2019 data offers a more comprehensive overview of prevalence, regional variations, and other epidemiological measures.
Economic Burden
IBD Economic Burden: USA
- Annual Direct Costs: Studies show a wide range, from $7,824 to $41,829 per patient annually. Outpatient costs comprise 19-45%, inpatient costs 27-36%, and pharmacy costs 7-51% of direct costs. Crohn's disease tends to have higher costs than ulcerative colitis. Indirect costs, largely due to presenteeism (reduced productivity while at work), also vary significantly.
- Lifetime Costs: One study estimated lifetime costs per patient to be $622,056 for Crohn's disease and $405,496 for ulcerative colitis. This translates to a staggering $498 billion and $377 billion for the respective prevalent populations in the US in 2016. These costs are highest for those diagnosed at a young age (0-11 years), reaching $707,711 for Crohn's and $369,955 for ulcerative colitis.
- Overall Costs: Estimates from 2014 put the total direct and indirect costs of IBD between $14.6 and $31.6 billion. More recent data suggests costs have nearly doubled in the last two decades and continue to rise due to increased prevalence and use of expensive biologics.
- Cost Drivers: Key cost drivers include specific therapeutics (biologics, opioids, steroids), emergency department visits, and services related to disease relapse, anemia, and mental health comorbidities.
- Financial Toxicity: A significant portion of IBD patients experience financial distress, with about 23% reporting financial hardship due to medical bills and 16% experiencing cost-related medication nonadherence. This distress is associated with lower education, lower income, public insurance, comorbidities, disease severity, and food insecurity. It can lead to delayed medical care, medication nonadherence, and reduced quality of life.
IBD Economic Burden: Europe
Specific data on the economic burden of IBD in Europe was not found in the provided PubMed abstracts. However, the provided information does offer insights into the global burden:
- Global Burden: In 2019, there were an estimated 4.9 million IBD cases globally. While the global age-standardized prevalence, death, and DALY rates decreased between 1990 and 2019, the age-standardized prevalence increased in 13 of 21 global regions and 147 of 204 countries/territories. The burden is higher in high socio-demographic index locations, although rates in these areas have declined since 1990. Conversely, rates have increased in middle and low socio-demographic index regions.
- Cost of Illness in Iran: A study in Iran found the mean annual cost per patient to be $1,077 for ulcerative colitis and $1,608 for Crohn's disease, with indirect costs accounting for the majority (58% and 63%, respectively). The national cost of illness was estimated at $22,331,079 for ulcerative colitis and $15,183,678 for Crohn's disease.
It's important to note that these global and Iran-specific figures cannot be directly extrapolated to Europe. Further research focusing specifically on European countries is needed to accurately quantify the economic burden of IBD in that region.
Drug used in other indications
Regulatory T cell (Treg) therapy is being investigated for various conditions beyond Inflammatory Bowel Disease (IBD). These include:
- Transplantation: Tregs are being explored to induce tolerance and prevent organ rejection. This includes both solid organ transplantation and hematopoietic stem cell transplantation. Trials are investigating the use of polyclonal Tregs, as well as antigen-specific Tregs designed to target donor antigens. The goal is to minimize or eliminate the need for lifelong immunosuppression, which carries significant side effects.
- Graft-versus-Host Disease (GvHD): GvHD is a serious complication of hematopoietic stem cell transplantation, where donor immune cells attack the recipient's tissues. Tregs are being studied to prevent and treat GvHD by suppressing the donor T cell response. Clinical trials have shown promising results in terms of safety and efficacy.
- Autoimmune Diseases: Besides IBD, Tregs are being investigated for other autoimmune diseases like Type 1 Diabetes, where the immune system attacks insulin-producing cells in the pancreas. Trials are exploring the use of polyclonal Tregs, as well as antigen-specific Tregs targeting autoantigens involved in the disease process. The aim is to restore immune tolerance and prevent further tissue damage.
- Other Conditions: Preclinical studies are also exploring the potential of Treg therapy for conditions like neurological disorders and tissue repair, although clinical trials in these areas are less advanced.
Intervention models for these trials vary depending on the specific condition and the stage of research. Common approaches include:
- Adoptive Transfer of Polyclonal Tregs: This involves isolating and expanding Tregs from the patient's own blood (autologous) or from a healthy donor (allogeneic) and then infusing them back into the patient. This approach is being used in trials for GvHD, transplantation, and various autoimmune diseases.
- Adoptive Transfer of Antigen-Specific Tregs: This involves engineering Tregs to recognize specific antigens relevant to the disease. This can be achieved by transducing Tregs with T cell receptors (TCRs) or chimeric antigen receptors (CARs) that target the desired antigen. This approach is being explored for transplantation and autoimmune diseases, with the goal of enhancing the specificity and efficacy of Treg therapy.
- In vivo Treg Induction/Expansion: This involves using drugs or other interventions to promote the development or expansion of Tregs within the patient's body. For example, low-dose IL-2 has been shown to selectively expand Tregs and is being investigated in combination with Treg adoptive transfer.
- Combination Therapies: Some trials are combining Treg therapy with other treatments, such as conventional immunosuppression in transplantation or disease-modifying therapies in autoimmune diseases. The goal is to enhance the overall therapeutic effect.
Clinical trials are ongoing to evaluate the safety and efficacy of these different Treg therapy approaches for various indications. While promising results have been observed in some cases, further research is needed to optimize Treg manufacturing, delivery, and monitoring, and to determine the long-term benefits and risks of this novel therapeutic strategy.