MARKET BRIEF - Allergic Rhinitis Immunotherapy: Opportunity Analysis & Forecasts to 2028

INTRODUCTION

Allergic rhinitis (AR) is a common inflammatory disease in which an individual reacts to an otherwise innocuous inhaled substance with symptoms including runny nose, sneezing, nasal congestion, and itchiness of the eyes, nose, and palate. In the seven major markets (7MM: US, France, Germany, Italy, Spain, UK, and Japan), the total prevalence of AR is estimated to be 15%-30% of the population — an enormous potential market size.

While a wide variety of over-the-counter (OTC) therapies exist for the temporary abatement of AR symptoms, allergen-specific immunotherapy (ASIT) is the only truly disease-modifying therapy available for AR. This therapy involves the gradual administration of allergens in increasing doses to desensitize patients over time. Although the immunomodulatory effects of ASIT are complex and not fully understood, successful immunotherapy has been linked to a shift from a Th2-skewed immune profile, characteristic of atopic conditions, to a more tolerogenic phenotype. The two most common forms of ASIT used in the treatment of airborne allergens are subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT).

Due to a number of factors, ASIT remains underused in the 7MM, but this may be beginning to change. The field is currently in a state of flux and the resultant changes will likely redefine the market going forward.

ALLERGIC RHINITIS IMMUNOTHERAPY MARKET FORECAST

Between 2018 and 2028, the AR ASIT market is expected to grow at a slow but steady pace. GlobalData estimates 2018 sales to be $901 million across the 7MM. By the end of the forecast period in 2028, sales are expected to increase to $1.1 billion at a compound annual growth rate (CAGR) of 2.3%. Overall, the key factor driving this growth is the anticipated approval and launch of five new pipeline therapies:

-Allergy Therapeutics’ Grass MATA MPL

-ASIT Biotech’s gp-ASIT

-Biomay’s BM-32

-ALK-Abello’s Itulazax

-Shionogi and Stallergenes Greer’s S-525606/STG-120

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While the first three products target grass pollen allergy using short-course preseasonal SCIT, the other two products target allergies toward different groups of trees using SLIT tablets. Despite this global trend toward growth, market dynamics are expected to vary greatly throughout the 7MM, reflecting unique, region-specific current and historical therapeutic trends.

In the five key European Markets (5EU: France, Germany, Italy, Spain, and UK), there is a heightening focus on the use of ASIT products with greater clinical accountability, particularly those with formal marketing authorization (MA). This ongoing shift away from a market dominated by named patient products (NPPs) makes room for new players from the pipeline, such as ASIT Biotech’s gp-ASIT, Biomay’s BM-32, and ALK-Abello’s Itulazax.

However, during the forecast period, GlobalData expects overall growth in this geography to be quite low (CAGR of 0.5%). This attenuated growth despite the launch of several new products is the anticipated result of a large number of NPPs leaving the market as well as the often slow-moving nature of national healthcare services in establishing coverage for ASIT products.

Even after the initial launch of SLIT tablet products several years ago, the US has remained quite resistant to the use of pre-formulated ASIT products, commonly used in Europe. US allergists instead tend to opt for the flexibility of formulating ASIT doses using bulk extracts. However, GlobalData believes that the potential launch of the first ultra-convenient, short-course, preseasonal SCIT product, Allergy Therapeutics’ Grass MATA MPL (previously known as Pollinex Quattro Grass), during the forecast period could inspire patients, physicians, and payers to utilize new methodologies. Due to an expected modest increase in the use of and new introduction of more costly pre-formulated ASIT products, GlobalData expects that growth will be particularly pronounced in the US, with a CAGR of 8.7%. This includes the expected launch of Grass MATA MPL in 2023, the continued uptake of the recently launched house dust mite (HDM) tablet, Odactra, and the launch of a second HDM tablet, Stallergenes Greer’s Actair, in 2020. This last product has been marketed in Japan for several years and is only recently in clinical development for the 5EU and US.

Since the launch of several pre-formulated SLIT products in Japan in 2014, the size of the ASIT market in this country has been steadily growing. The recent launch of Torii’s Japanese cedar pollen (JCP) SLIT tablet, Cedarcure, and the expected launch of Shionogi’s S-525606, also for the treatment of JCP allergy, is expected to continue to expand the market size potential in Japan. In Japan, strong market growth (CAGR of 4.8%) is expected during the forecast period, associated with the increased use of marketed SLIT tablet products for both HDM and JCP allergies, as well as the launch of a second JCP SLIT tablet product, S-525606, in 2023.

PIPELINE PRODUCTS SEEK TO MAKE ASIT QUICKER & MORE CONVENIENT

Currently, only a small portion of AR patients who are eligible for ASIT will actually be treated. One key factor driving low treatment rates is the inconvenience associated with receiving the therapy over the course of multiple years. In response to this ongoing issue, companies have invested greatly in R&D efforts to create products that act faster, are more effective, and give patients flexibility in their dosing regimen. This effort can plainly be seen in the current AR ASIT pipeline.

To improve the convenience of SCIT, an ongoing trend in the 5EU has been the development of products that require fewer doses and thus fewer visits to the allergy specialist. These products typically consist of allergens specially formulated to be hypoallergenic, thus allowing for the safe injection of higher doses. One example of this type of product seeking MA in the US and EU is Grass MATA MPL, which is an allergoid formulation of 13 grass pollens combined with a microcrystalline tyrosine (MCT) depot and a monophosphoryl lipid A (MPL) adjuvant. The current pipeline also includes SCIT products utilizing other methods to improve efficacy and diminish allergenicity.

For example, both ASIT Biotech’s gp-ASIT and Biomay’s BM-32 use hypoallergenic allergen peptide fragments. However, the products differ in that gp-ASIT uses natural, hydrolyzed peptide fragments from Lolium perenne pollen, while BM-32 uses a fusion protein consisting of recombinant peptides targeting key B-cell epitopes for Phleum pretense pollen and an immunogenic carrier protein.

US and 5EU key opinion leaders (KOLs) were especially enthusiastic about these new short-course, pre-seasonal grass pollen SCIT products, particularly Grass MATA MPL and gp-ASIT. They believed that the therapies would be more convenient for patients and that the shortened duration of therapy could improve long-term compliance. However, while US KOLs seemed optimistic about gaining access to these new pre-formulated SCIT products, they also seemed unwilling to completely overhaul the way they administer ASIT. US KOLs believed that the use of bulk allergens would remain the dominant way for ASIT to be administered in the country. They reasoned that bulk allergens can be used to formulate mixtures of allergens for polysensitized patients while new, pre-formulated products only target a single allergen. Additionally, KOLs noted that there was a financial incentive for keeping ASIT methodologies the same: US allergists can charge fees for the formulation of allergen extract mixtures in-house, which provides a substantial source of renewable income for small practices. Another major strategy to address low treatment rates in the AR ASIT space is to increase the availability and usage of SLIT products. Because of a lessened risk of serious adverse events, SLIT can be self-administered by patients at home. While SLIT drop products have been available for some time in the 5EU, throughout the past decade the SLIT market is steadily being overtaken by SLIT tablets administered once daily. These tablets, mainly developed and marketed by Stallergenes Greer and ALK-Abello, were subjected to rigorous clinical development programs and as a result, have been granted formal MA in multiple countries throughout the 7MM. While these SLIT tablets have been very successful in Japan and the 5EU, their uptake in the US continues to be less than expected. This is mainly due to poor insurance coverage for the products, as well as a continued focus of US allergy specialists on the use of multi-allergen SCIT formulated from bulk allergen extracts. ALKAbello’s Itulazax for birch homologous tree pollen allergy and Shionogi and Stallergenes Greer’s S-525606/STG-120 for JCP allergy make use of ALK-Abello’s and Stallergenes Greer’s tried-and-tested tablet formulations found in products like Grazax and Oralair, respectively.

KOLs from Japan stressed the growing importance of SLIT in their country. Since the introduction of SLIT tablet and drop products for HDM and JCP allergens several years ago, KOLs noted that the use of ASIT was steadily increasing and would likely continue to increase in years to come. KOLs explained that patients were happy with the relief they were getting from these products and the news was quickly spreading by word of mouth. Japanese KOLs also specified that the increased safety profile of SLIT made physicians more willing to introduce the therapy into their practices.

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UNMET NEEDS STAND AS KEY BARRIERS TO GROWTH

Despite being the only disease-modifying therapy available for the treatment of AR, ASIT remains underused. These low treatment rates severely limit the full potential for growth in this market. KOLs interviewed by GlobalData suggested this is in great part due to a number of lingering unmet needs in the field, standing as barriers to increased uptake. These barriers include inadequate access, a shifting regulatory landscape, and low treatment compliance and persistence.

First, in the US and 5EU, KOLs highlighted cost and inadequate insurance coverage as two of the main issues driving this lack of usage. With effective and inexpensive OTC drugs for AR readily available on the market, KOLs explained that private and public insurance providers are often less willing to pay for ASIT. One KOL from the US believed that if ASIT was made more affordable, it could easily double the number of patients receiving the therapy. KOLs from throughout the 7MM agreed that the financial burden of ASIT was a key factor in stifling patient initiation of ASIT as well as promoting early discontinuation. In the 5EU and Japan, KOLs also linked underutilization of ASIT to inadequate access to allergy specialists who were able and willing to offer the therapy. In the 5EU, KOLs stressed the need for increased funding for allergy specialty training, while in Japan they noted the lack of financial incentives for allergy specialists to offer ASIT in their practices.

KOLs interviewed by GlobalData also noted that the regulations governing the use and development of ASIT products require some significant changes. This sentiment was particularly strong in the 5EU, where unregulated NPPs fill the marketplace. KOLs from the 5EU noted a growing preference both by physicians and governmental authorities for drugs with a formal MA rather than NPPs. This movement towards increased standardization in ASIT product regulation in the EU took root in Germany in 2009 via enactment of the Therapie-Allergene-Verordnung (TAV), which required NPPs for certain key allergens to obtain formal MA within a given time frame. One 5EU KOL noted that those actions have since transformed the German ASIT market, which now focuses heavily on products with MA. 5EU KOLs believed that the rest of the EU was beginning to move in this direction. Although they felt this trend would be good for the market as a whole, they noted that the number of available products would shrink drastically. However, these KOLs argued that by ensuring only the safest and most effective products were available on the market, a stronger ASIT market would take shape in the future.

Finally, KOLs highlighted the need for patient compliance and persistence to improve. There are a variety of known factors affecting patient compliance to ASIT, half of which involve practical considerations such as method of administration, side effects, and cost, while the other half involve more nuanced factors such as the attitude of the patient and relationship with their physician. Along with the potential availability of more convenient, efficacious ASIT products in the future, KOLs noted that improving relationships between patients and their doctors could be a helpful move. For example, patients receiving SCIT tend to demonstrate better compliance in comparison to those receiving SLIT. KOLs explained that this is in large part due to the fact that SCIT requires patients to visit their doctor regularly, an ongoing relationship that likely improves treatment compliance and persistence.

NEW DEVELOPMENTS

Since the publication of GlobalData’s report, Allergic Rhinitis Immunotherapy: Opportunity Analysis and Forecasts to 2028, it was announced that the grass pollen SCIT product, gp-ASIT, failed its latest Phase III trial. While the future for this particular product is no longer clear, GlobalData believes that the overall size and trends of the grass pollen ASIT market will remain as projected, with other pipeline grass pollen SCIT products claiming the sales originally anticipated for gp-ASIT.

Dr. Rose Joachim is a Senior Healthcare and Pharmaceutical Analyst at GlobalData in Boston. In 2017, she earned her PhD in Biological Sciences in Public Health at Harvard University. Her dissertation research explored the effects of age on immune system function during sepsis. When she wasn’t at the bench, she spent her time teaching and developing new science curricula as part of the Science Education and Academic Leadership certificate program at Harvard. Prior to her graduate studies, Dr. Joachim earned her BS in Biology with a minor in Chemistry from The College of New Jersey.