In respiratory diseases, it is all about delivery
November 28, 2018 | Disease
When Vectura’s nebulised form of budesonide, VR475, failed its Phase III asthma trial in late November 2018, the UK company blamed the drug, not the device. A conventional nebulizer also failed to significantly impact exacerbations, versus placebo.
In respiratory diseases, like in some corners of diabetes, the delivery device often does matter more than the drug. Many of the active substances have been around for decades. Among patients with conditions like asthma and chronic obstructive pulmonary disease, outcomes are hugely dependent on correct use of inhaler devices. That has been shown in real world studies, such as the CRITIKAL asthma review, published in 2017.
The problem is that devices can be tricky to use. Several require patients to follow a multi-step process, inhale with just the right force at just the right time, and even then it may not be clear whether the dose has been taken. Many physicians do not know how to use them, either.
So the competition is around who can offer the most convenient, easy-to-use delivery device – one shown to generate the best adherence data, fewest medication errors and thus lowest medication wastage among a given patient group.
Vectura hopes the ‘guided inhalation system’ technology used in VR475 may yet find its place among younger asthma sufferers. The system guides patients through a series of slow, deep breaths and notifies them when treatment is complete, logging adherence data in an app, too. Phase II data for VR647 earlier in 2018 suggested that children found the breath-activated delivery system easy to use, with little or no loss of medication.
Meanwhile, Vectura’s partner Mundipharma in September 2018 launched the easy-to-use flutiform k-haler in the UK, with further European launches expected over the coming months. The k-haler delivers a well-known drug duo of inhaled corticosteroid and long-acting B2 agonist (LABA). But its sponsors claim it is more user-friendly than conventional metered dose inhalers, requiring only gentle inhalation to trigger dose release, rather than the high inspiratory force needed for dry powder inhalers. The result, the companies say, is fewer inhaler errors, and better outcomes for patients.
Delivery may also help determine the winner in another competitive respiratory sub-category: injectable therapies for severe asthma. GlaxoSmithKline, AstraZeneca, Teva,
Novartis/Roche and Sanofi/Regeneron all have monoclonal antibody therapies in this space: Nucala (mepolizumab), Fasenra (benralizumab), Cinqair (reslizumab), Xolair (omalizumab) and Dupixent (dupilumab), respectively. Dupixent, an excema drug only recently approved by FDA for moderate to severe asthma, may have the edge, even though it is last to the party.
That’s because, as a pre-filled syringe for sub-cutaneous injection, it is the only one that can be delivered at home. There will be other factors in play, though: Fasenra is given only once every eight weeks, while Dupixent is administered every other week. (The others are once-monthly). Pricing will also play a big role in the battle among these £30-40,000-a-year injectables, and they may soon face a new competitor as AZ/Amgen receive FDA breakthrough designation for tezepelumab, which could serve a broader range of patients.
Finally, delivery systems are driving some unusual dynamics post-Advair, too: sales of GSK’s blockbuster continue to erode, but more slowly than many anticipated, and not because of true generics. Several generic candidates have been delayed at FDA due to challenging bioequivalence hurdles – it is tough to re-produce GSK’s Diskus delivery device. So Teva in 2017 launched a drug-device combo using its own RespiClick device, called AirDuo RespiClick. That cannot be substituted for Advair. But Teva simultaneously launched its own, cheaper, substitutable generic of AirDuo RespiClick, effectively delivering the lower-cost alternative that many payers and patients were waiting for.
- March, 20 2020