Xolair for food allergies: effective therapy at a high price

Food allergies affect 5-10% of the American population. Their prevalence continues to increase, with significant quality-of-life impairments for patients and their families[1]. It is a unique indication in that patients are not chronically ill, but acute illness can occur within minutes even with proper precautions. Death is extremely rare[2].  For decades, the space has seen little in the way of treatment, with the cornerstone of management being strict allergen avoidance. Oral immunotherapy is an option to desensitize patients to their allergens, but it is burdensome and carries risk of allergic reactions and high discontinuation rates[3]. Xolair (omalizumab, anti-IgE antibody, Genentech/Novartis) offers high clinical benefit, safely increasing the amount of allergen that patients can tolerate without experiencing symptoms of severe allergic reactions that can occur through accidental exposure.

Xolair is incredibly efficacious in this indication, with modest safety/tolerability and convenience drawbacks. Even though it comes with a black box warning for anaphylaxis, safety is a minor concern in practice- it boasts a mild side effect profile and its safety is well established, as it has been on the market for more than 20 years in other indications.

Xolair also confers benefit in common comorbid allergic conditions, such as rhinitis, asthma, and eczema. Xolair comes as a metered-dose autoinjector or prefilled syringe that can be administered at home approximately every other week or every four weeks, depending on baseline IgE levels and body weight, and must be administered indefinitely for continued benefit. Typically, drugs with clinical innovation of 5% or more go on to achieve reasonably strong patient share. Xolair in this indication has very high clinical benefits, but at a steep price of around $100,000 a year. We anticipate strong interest from patients and physicians, but strong push-back from payers.

Xolair will likely become a candidate for biosimilar development when it goes off patent within the next few years, which will likely mitigate the high price and expand access in this poorly served indication. 

[1] https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2022/20220126.htm

[2] Umasunthar et al. 2013

[3] Mori et al. 2021

Evrysdi: A Potential Game-Changer for SMA Type 1 Patients

Spinraza was the first effective treatment option for Spinal Muscular Atrophy (SMA) Type 1.  Zolgensma and Evrysdi are reshaping the market because of their superior efficacy.

SMA Type 1 is a rare, debilitating genetic disorder, affecting about 1 in 10,000 live births, with symptoms beginning before six months of age. Historically, infants born with this disorder could not sit without support.  Most were expected to live two years or less.

The FDA approval of Spinraza (nusinersen, Biogen) in 2016 finally offered hope to families. The ENDEAR trial of Spinraza had such positive results that it was terminated early to give all participants access to Spinraza in an open-label extension (SHINE). Since then, Zolgensma (onasemnogene abeparvovec, Novartis, approved 2019) and Evrysdi (risdiplam, Roche, approved 2020) have emerged as alternative treatment options.

Like Spinraza, Evrysdi is a chronic treatment. However, it offers several benefits over Spinraza. In infantile-onset, symptomatic SMA Type 1 patients less than two years old, Evrysdi has noticeably higher efficacy (event-free survival and motor milestone response). These gains reduce mortality and morbidity. Evrysdi is a daily oral therapy, more convenient than Spinraza’s intrathecal bolus route.

Evrysdi is dosed by kg/bodyweight, with an annual price cap not to exceed that of treating a 44 lb child, complicating any simple cost comparison. However, even at its maximum price, the annual cost of Evrysdi is less than that of maintenance Spinraza.

In the Equinox model, Evrysdi offers 15.1% clinical innovation versus Spinraza. Historically, drugs that have scored >10% clinical innovation have become market dominators, and so far, annual sales of Evrysdi have trended in this direction.

One way that Spinraza has an edge over Evrysdi is its quantity of supporting data, since Evrysdi has not been around as long to establish a track record.

Zolgensma is another promising treatment option for SMA type 1. Unlike Spinraza and Evrysdi, Zolgensma is a single-dose gene therapy. At approximately $2.25 million 2023 USD (WAC, Micromedex), its price tag has been criticized in the past. However, Novartis offers different payment plans, including outcome-based and over-time payment plans, both up to 5 years.

Spinraza and Evrysdi (at maximum dose) overtake that $2.25 million mark after about 5 and 6 years of treatment, respectively. However, this calculation ignores other direct costs (such as hospitalization) and the potential for additional therapies if the initial treatment is insufficient. This added cost is worth considering since recent data shows that 7.5 years after dosing, almost one-third of Zolgensma-treated patients had received follow-up treatment. Unlike Spinraza and Evrysdi, a patient cannot simply switch off of Zolgensma if it does not perform as expected. Discounts, negotiations, and payer willingness to sponsor an expensive one-time therapy like Zolgensma also complicate the picture.

In summary, in a head-to-head comparison against Spinraza, Evrysdi is the clear winner. This sets it up to become a future standard-of-care as data continue to accumulate. Zolgensma is also innovative over Spinraza. However, it will likely continue to face challenges as payers continue to negotiate the best way to finance an expensive one-time treatment where a cost-effective outcome cannot always be guaranteed.