In a recent interview with PharmaShots, Ted Omachi, Global Development Leader for Xolair, and Senior Medical Director of Product Development for Immunology, Genentech shared his views on the approval of Xolair in the US.

Shots:

• The approval is based on P-III POLYP 1 & 2 trials assessing Xolair vs PBO in 138 & 127 adult patients with nasal polyps who had an inadequate response to nasal corticosteroids respectively
• Results: @24wks. improvement in NPS (-1.1 vs 0.1 & -0.9 vs -0.3); improvement in NCS (-0.9 vs -0.4 & -0.7 vs -0.2); no new or unexpected safety signals were identified respectively
• Xolair is the first biologic for the treatment of nasal polyps that targets and blocks IgE. In the US, Novartis & Genentech work together to develop and co-promote Xolair

Tuba: Can you please shed some light on Nasal Polyps? (causes, symptoms, epidemiology, etc.)

Ted: Approximately 13 million people in the U.S. are impacted by nasal polyps, a commonly occurring condition in adults that may be refractory to treatments such as nasal corticosteroids and even surgery. Nasal polyps present as noncancerous growths on the lining of the nasal sinuses or nasal cavity associated with irritation and inflammation and, as such, they can block normal airflow. Nasal polyps may also co-occur with other respiratory conditions, such as allergies and asthma. They may become quite large and develop in both nostrils, leading to a loss of smell, nasal congestion, chronic runny nose, and post-nasal drip. This condition can cause significant long-term symptoms and impact on patients lives. While the pathophysiology of nasal polyps is not entirely elucidated, we know that it is an inflammatory condition in which immunoglobulin E (IgE) plays an important role.

Tuba:  A quick highlight of clinical data submitted for the approval of Xolair in nasal polyps to the U.S. FDA.

Ted: The FDA's approval is based on results from the Phase III POLYP 1 and POLYP 2 pivotal trials conducted in adult patients. To be enrolled in the study, patients needed to have large polyps in both nostrils and significant symptoms, with persistent symptoms and large polyps even after treatment with nasal steroids. Patients were then given either Xolair or placebo, in a blinded fashion, while continuing to receive nasal steroids. Patients who received Xolair had statistically significantly greater improvements, as compared to placebo, over the approximate six-month duration of the study, from baseline to Week 24, in both of the co-primary endpoints: Nasal Polyp Score (NPS) and Nasal Congestion Score (NCS). NPS is an objective measure of the size of the polyps, as determined by endoscopy, while NCS is a measure of the degree of nasal blockage, as determined by patients' assessment of their own symptoms. The greater improvements in NPS and NCS in the Xolair group as compared to the placebo group were observed as early as the first assessment at Week 4 in both studies. They also had statistically significant improvements in smell, post-nasal drip, and runny nose. The safety profile in POLYP 1 and POLYP 2 was consistent with the established safety profile for Xolair, which is based on more than 17 years of real-world experience in allergic asthma and more than 1.3 million patient-years of usage in clinical practice. 

Tuba: Can you explain how Xolair works for nasal polyps (mechanism of action)?

Ted: Xolair is the first biologic for the treatment of nasal polyps that targets and blocks immunoglobulin E (IgE), a key driver of inflammation. By reducing free IgE, down-regulating high-affinity IgE receptors and limiting mast cell degranulation, Xolair minimizes the release of mediators throughout the allergic inflammatory cascade.

Tuba: Can you provide some insights on RoA for Xolair in Nasal Polyps?

Ted: We do not comment on sales forecasts or projections.

Tuba:  Can our readers have more details on any ongoing and upcoming patients support programs and efforts for patient adherence?

Ted: As a physician, I know firsthand that adherence and access to medicines are some of the most important factors to ensure the safety and effectiveness of treatment for patients. At Genentech, we are committed to helping patients access to the medicines prescribed by their physician, even if they can't afford them. For more than 20 years, we have helped more than 2.2 million people get the medicine they need through patient assistance programs like Genentech Access Solutions and the Genentech Patient Foundation.

Tuba: Xolair is now approved in multiple indications including allergic asthma, CIU and nasal polyps. What's next?

Ted: We are committed to exploring the full potential of Xolair across a range of respiratory diseases.

In August 2020, the FDA accepted our sBLA for a new self-injection option for Xolair prefilled syringe formulation across all approved US indications, with a decision on approval anticipated in Q1 2021.

Additionally, in 2018 the FDA granted Breakthrough Therapy Designation to Xolair as a potential treatment for food allergies. Xolair is currently being investigated as a potential treatment for multiple food allergies in Phase III clinical trial, Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen Oral Immunotherapy in Food Allergic Children and Adults, or OUtMATCH trial. The trial is supported by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, Genentech, and Novartis. We are hopeful about the potential to address this area of the significant need for patients as there are limited FDA-approved treatments that help prevent severe reactions due to food allergies.

Tuba: Are you focusing on approvals in different countries?

Ted: Xolair is approved for nasal polyps-related conditions in several countries outside of the U.S. In August 2020, the European Commission approved Xolair as add-on therapy with intranasal corticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps (CRSwNP) for whom therapy with intranasal corticosteroids does not provide adequate disease control. Additionally, Xolair is approved in more than 10 other countries throughout the world for nasal polyps or CRSwNP. Further regulatory reviews of Xolair to treat patients with CRSwNP (often referred to as nasal polyposis) are currently underway in multiple countries.

Tuba: What kind of pricing difference shall be expected for Xolair for Nasal Polyps vs. Xolair for other indications?

Ted: When determining the prices of our medicines, we take into consideration a number of factors including clinical benefit, patient access, investments required for future medications, and our responsibility to patients, society, and shareholders. The dosing of Xolair for nasal polyps and allergic asthma depends on the patient's weight and serum IgE levels, which affects the cost of therapy.

About Ted Omachi:

Ted Omachi is a Medical Director in the Product Development Immunology group at Genentech, focusing on late-stage development in respiratory and allergic diseases. He joined Genentech in 2013, starting in the Medical Affairs group before transitioning to Product Development in 2015.

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