[BLOG]: Potential impact of novel pipeline therapies entering the uncharted celiac disease market

Garg

Celiac disease occurs due to a genetic intolerance to dietary ingested gluten peptides. This initiates an immune response, predominantly in the small bowel, that results in malabsorption and associated symptoms including chronic diarrhea with weight loss, steatorrhea, postprandial abdominal pain, and bloating. The effects of the disease can progress to the development of extraintestinal symptoms such as anemia, bone disease, infertility, unfavorable outcomes of pregnancy, lymphoma, and liver disease, although patients can be asymptomatic at times. Furthermore, a subset of celiac patients can suffer from a refractory form of the disease known as type 1 or type 2 refractory celiac disease (RCD), which is characterized by the development of abnormal intraepithelial lymphocytes and usually leads to lymphoma. GlobalData estimates that in 2014, the total prevalence of celiac disease reached 6 million, of which there were approximately 0.8 million diagnosed celiac patients in the 6 major pharmaceutical markets (6MM) (United States, France, Germany, Italy, Spain, United Kingdom).^1,2

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The current standard of care for nonrefractory celiac patients is the complete exclusion of gluten from the diet, known as a gluten-free diet (GFD).³If followed strictly, a GFD can stop and reverse the effects of gluten-induced injury to the small bowel. Although following a GFD appears to be a straightforward process, it can actually be problematic and inconvenient due to the presence of gluten in most foods, which means there is an immediate need for pharmacological intervention in celiac disease patients.

The current global celiac disease market is naïve, with no disease-specific drugs available to date. Instead, it is dominated by generic steroids and immunosuppressant drugs. GlobalData estimates that sales for celiac disease were approximately $52.2 million in the 6MM in 2014.²Steroids and immunosuppressants are used mainly to treat patients suffering from RCD or for very severe cases of celiac disease. Not surprisingly, the annual cost of drug treatment is very low, as the current pharmacological interventions are inexpensive and are not commonly used due to their well-documented adverse effects.

Drugs in Perspective: Pipeline data

Two novel pipeline drugs that have the potential to launch in the next 5 years and rapidly increase the value of the celiac disease market are Alba Therapeutics/Teva’s larazotide acetate (AT1001) and Alvine Pharmaceuticals/AbbVie’s latiglutenase (ALV003). GlobalData predicts the launch of larazotide acetate in the US in the first quarter of 2018. This could be potentially followed by the launch of latiglutenase (ALV003) simultaneously in the US and the 5 European Union (5EU) countries of France, Germany, Italy, Spain, and the UK in the first quarter of 2019, bringing celiac disease sales in the 6MM to approximately $290 million in 2019. The 5EU launch of latiglutenase is anticipated in the first quarter of 2020, and may boost the 6MM sales to around $343 million, followed by a steady increase to about $551 million by 2023. As such, the value of the celiac disease market has the potential to expand more than 10-fold between 2013 and 2023, at an impressive compound annual growth rate of 27.2%, which will be driven mainly by the potential introduction of these aforementioned late-stage pipeline candidates and the increasing prevalent cases of the disease. The US is anticipated to be the key contributor to the overall sales growth, as the vast majority of the diagnosed population in the 6MM live in the United States.²

Focusing on the mechanism of action of the novel pipeline drugs, larazotide acetate is a tight junction modulator designed to reduce the absorption of toxic gluten peptides through the small intestine.⁴Latiglutenase, on the other hand, is a mixture of enzymes designed to break down gluten peptides into nontoxic forms.⁵Both products are designed to be used as adjunctive treatments to a GFD to minimize gluten exposure for nonrefractory celiac patients. There is a need for GFD adjunctive treatments for celiac patients who ingest gluten even when on a GFD, either through poor compliance or inadvertent exposure, which can equate to almost 100% of nonrefractory patients. These pipeline drugs would therefore target close to 93% to 96% of all celiac patients, compared with the 4% to 7% of patients who are currently treated with generic steroids and immunosuppressants.²

Shining a spotlight on the early-stage, clinical celiac disease pipeline reveals another adjunctive therapy to a GFD, namely, BioLineRx’s BL-7010, which is due to enter phase 2b in the second half of 2015. BL-7010 is a synthetic polymer designed to bind gluten peptides and prevent their absorption into the body.⁶The only potentially preventive product that is in clinical development is ImmusanT’s Nexvax2. This product is in the early stages of clinical development and will serve as a vaccine for patients with the HLA-DQ2 genotype, who make up more than 90% of the celiac patient population.⁷

The launch of adjunctive pharmacological therapies in the celiac disease market is greatly anticipated.⁸Most celiac patients are exposed to gluten, even when on a GFD, and the effects of this exposure can range from temporary discomfort to severe symptoms. Key obstacles in effectively treating these patients include a lack of awareness of foods that contain gluten and how to manage issues that lead to poor patient compliance with a GFD.²The availability of specially manufactured gluten-free foods can help enhance compliance with a GFD, but as well as being expensive, these foods are often unpalatable. The gluten-free food industry is quickly growing and developing at a fast rate to try and overcome issues it faces, including poor palatability and a lack of variety. In the US, the gluten-free food industry was valued at $10.5 billion in 2013 and predicted to rise to $15.6 billion by 2016.⁹The cost of drugs that will be used as adjunctive treatments to a GFD is likely to be low, due to the chronic nature of the condition and in order for them to be affordable for patients, who are usually already purchasing expensive gluten-free foods. These adjunctive treatments target a large patient population, however, which will likely also contribute to the huge increase in the celiac disease market value by 2023.

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The impending entry of adjunctive therapies in the celiac disease market could lead to increased patient awareness and improved physician diagnosis of the condition. Consequently, the size of the diagnosed patient population may also rise. Currently, the celiac disease patient population is massively underdiagnosed, as the diagnosed prevalent cases across the 6MM in 2014 were only 13% to 15% of the total disease prevalence.²The diagnosis of celiac disease can be a complex process, and a possible reason for the current low diagnosis rate could be a lack of physician education regarding proper diagnosis. Alternatively, improved physician education regarding a GFD, along with a growing gluten-free food market, may refine the current standard of care, which may, in turn, deter physicians from prescribing adjunctive treatments for patients with celiac disease.

References

EpiCast Report: Celiac disease–epidemiology forecast to 2023. London, UK: GlobalData; November 2014.

Opportunity Analyzer Report: Celiac disease–opportunity analysis and forecast to 2023. London, UK: GlobalData; November 2014.

Rubio-Tapia A, Hill ID, Kelly CP, et al. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol. 2013;108(5):656–676.

Leffler DA, Kelly CP, Abdallah HZ, et al. A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge. Am J Gastroenterol. 2012;107(10):1554–1562.

Lähdeaho ML, Kaukinen K, Laurila K, et al. Glutenase ALV003 attenuates gluten-induced mucosal injury in patients with celiac disease. Gastroenterology. 2014;146(7):1649–1658.

McCarville JL, Nisemblat Y, Galipeau HJ, et al. BL-7010 demonstrates specific binding to gliadin and reduces gluten-associated pathology in a chronic mouse model of gliadin sensitivity. PLoS One. 2014;9(11):e109972.

de Kauwe AL, Chen Z, Anderson RP, et al. Resistance to celiac disease in humanized HLA-DR3-DQ2-transgenic mice expressing specific anti-gliadin CD4+ T cells. J Immunol. 2009;182(12):7440–7450.

Tennyson CA, Simpson S, Lebwohl B, et al. Interest in medical therapy for celiac disease. Therap Adv Gastroenterol. 2013;6(5):358–364.

Report: Gluten-free foods–US. London, UK: Mintel Group; September 2013.

Dr Garg is an analyst for GlobalData covering immunology.