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Only lasting approximately 20 years, the patents of many biologic blockbusters are nearing expiry in the next decade. As the cost of developing a biologic is around $800 million and the process can take an average of 8-10 years, originator companies are turning to drug product (DP) reformulation to maintain a competitive advantage.
By redeveloping a DP and changing a biologic’s method of administration, biotechs can produce patient-centric alternatives such as oral, nasal and inhaled products. By easing DP delivery and increasing access, redevelopment provides a long-term solution to overcome the rising biosimilar market and maximises investment in blockbuster biologics.
In this article, Ross Errington, Head of Drug Product Development at Recipharm, explores the growth of the biosimilar market and its role in driving the demand for biologic redevelopment, focusing on the move towards inhaled biologics as a solution.
Biosimilars drive DP redevelopment
The biosimilar market has experienced ample growth in recent years. Compared with biologic development, the costs of producing a biosimilar are significantly lower, approximating $100 to $200 million over the 8-10-year time frame. This makes biosimilar development a good investment. As a result, the biosimilar market is predicting an accelerated compound annual growth rate of 15.9% until 2030, from $21.8 billion in 2022.
Having experienced record sales of $21.2 billion in 2022, the blockbuster drug Humira will lose exclusivity in 2023, making it a prime target for biosimilar development. As a biosimilar maintains the same route of administration as the original DP, originator companies must look towards alternative methods of delivery to maintain a competitive advantage. Producing patient-centric alternatives offers this market edge, easing patient access and increasing adherence while the newly formulated DP regains exclusivity rights.
An example of this alternative approach is the move towards inhaled biologics. These systems allow for easy delivery of essential DPs within the patient’s home, not only increasing adherence for those averse to injections but also reducing the reliance on healthcare professionals. In addition, the inherent complexity of these products also makes it unlikely that a competitor will have the required knowledge to develop an inhaled biologic version of the DP. Only one inhaled biosimilar product is currently available on the market, which is the cystic fibrosis therapeutic Pulmozyme®, although exclusivity was lost in the US in 2015 and in Europe in 2019.
Inhaled biologics as a solution
Due to their sensitive nature, biologic products have traditionally been limited to parenteral delivery methods. When injected, these products bypass the harsh environment of the gastrointestinal (GI) tract that could cause degradation and loss of therapeutic activity. However, innovation in inhaled and nasal delivery systems, such as soft mist inhalers (SMIs), has led to a rise in interest in utilising these systems for the delivery of biologic DPs. These inhaled products offer many benefits, including:
Avoidance of the GI tract: Similar to parenteral methods, inhalation avoids the harsh conditions of the stomach.
- A large absorption area: The lung mucosa has a large absorption area (130 m²) that is highly vascularised.
- Direct delivery: Inhaled products provide efficient systemic delivery of the DP to the bloodstream while offering direct access to the brain, bypassing the blood-brain barrier.
By redeveloping a parenteral route to an inhaled product, patient convenience and experience are also optimised with this non-invasive, better-targeted method of delivery.
In addition, as the drug substance (DS) has already been approved by the regulatory authorities, the process of approval is eased, streamlining development and manufacture for a quick and efficient market launch.
Current limitations hinder inhaled delivery
However, despite the DS having already been through development and approval, redevelopment into inhaled and nasal products may prove difficult as biologics are complex materials.
The shear force applied when actuating a device can put the DP under stress, leading to damage to the biologic and loss of therapeutic activity. The device used must therefore undergo extensive optimisation to tailor it to the product at hand to ensure that the drug is delivered safely, effectively and with uniformity.
Biologics are not compatible with excipients ordinarily used in nasally-inhaled products, such as the standard preservative benzalkonium chloride, and so alternative solutions must be developed. This extends to the excipients conventionally added to parenteral systems not translating to inhaled or nasally-delivered products. Therefore, when developing an inhaled or nasal biologic, extensive compatibility testing is essential.
Overcoming challenges with device innovation
Innovations in SMIs offer a solution to overcome some of the challenges hindering inhaled biologic progress. These developments minimise the need for tailoring devices, offering a more off-the-shelf approach. These new devices produce a slow-moving aerosol, optimising liquid delivery of the drug. Advances in SMI and nasal spray inhaler design have also improved:
Next-generation spray nozzle: Reduced force required to aerosolise the DP reduces the likelihood of product damage.
- Lung dosage: A high dose is delivered to the lungs with a low systemic dose. This targeted approach reduces the systemic side effects and enhances the therapeutic index by delivering locally to the diseased site.
- Targeting: The use of spray nozzle technologies improves targeting of specific lung or nasal regions.
- New device platform: Innovative device design allows for adjustments to the spray cone without redesigning the SMI or inhaler devices.
Looking ahead in biologic delivery
With the impending biosimilar market growth, the redevelopment of blockbuster biologics provides a solution to maintain a market advantage. For biologics, inhaled or nasal administration looks particularly promising as an alternative delivery method. Providing a more patient-centric approach, inhaled and nasal delivery device innovation is aiding the move towards utilising these delivery systems for biologics.