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This new generation of biologic medicines promises to offer a multitude of benefits, but what exactly are they and how can manufacturers navigate regulatory processes to ensure availability for those who need them?

Patients with debilitating long-term medical conditions such as rheumatoid arthritis, Crohn’s disease and psoriasis are likely to be familiar with – and thankful for – a generation of powerful hospital treatments known as biologics, which are made from proteins or other components of living organisms.

First approved in the US by the Food and Drug Administration in the 1980s, they were followed by biosimilar drugs, which mirrored the characteristics and function of existing biologics but were usually cheaper than the reference product because of comparatively lower development costs. This not only created more choice for prescribers and patients but also introduced increased competition that succeeded in reducing treatment costs for healthcare

providers.

It’s no exaggeration to say that biologics and biosimilars have revolutionised medicine. Now, thanks to technological advances, these types of treatments have evolved into a new generation of biosimilars that offer further improvements.

While there is no official term for these innovative biosimilars, they are often known as biobetters.

Biosimilars are highly similar to their reference product in terms of quality, efficacy and safety, and must meet the same standards as the biologic. But biobetters go one step further – they have been tweaked to include specific attributes that deliver improvements for patients, medical staff and healthcare systems, for example, chemical modifications that can increase a drug’s half-life, lessen the body’s immune response or change a medicine’s delivery method to make it more convenient.

Put simply, biobetters could enhance patients’ quality of life, lead to better clinical outcomes and further reduce the cost burden on healthcare systems, addressing unmet needs and offering alternatives to existing treatments for both patients and healthcare professionals.

Take the immunotherapy drugs obinutuzumab and infliximab for example. Obinutuzumab is a biobetter developed from rituximab, which is used to treat inflammation in autoimmune diseases such as rheumatoid arthritis and some blood-cell cancers. Obinutuzumab has a different mechanism of action and studies have indicated improved clinical outcomes as well as higher cost-effectiveness compared to the reference product. In the case of infliximab, the subcutaneous - or under the skin - formulation demonstrated improved pharmacology parameters compared to its intravenous formulation with a different administration method.

"Biobetters could enhance patients’ quality of life, lead to better clinical outcomes and further reduce
the cost burden on healthcare systems."

For those with autoimmune conditions that require long-term management, biobetters that can be delivered subcutaneously by self-administered injection, offer flexibility and remove the need to regularly travel to treatment centres. They also reduce demand for hospital beds and staffing costs to monitor patients.

Professor Shomron Ben-Horin, Director of the Institute of Gastroenterology at Sheba Medical Center in Israel, comments: “Recent studies have also shown that regular subcutaneous administration can result in more sustained therapeutic drug levels rather than experiencing drops below the target level, as can be seen with intravenous infusion, therefore offering the potential for improved patient outcomes.”

"Critics argue that a globally accepted, standardised set of regulatory guidelines would avoid duplicating
clinical trials and allow medicines to come to market in a more timely fashion."

Despite the maturing of the biobetters market, there are still disparities between the approvals process in the EU and the US, as Dr HoUng Kim, Head of the Medical and Marketing Division at Celltrion Healthcare, explains:

“To date, there is no standardised guidance available from major regulatory agencies regarding the approval pathways for innovative biosimilar drugs. While the EMA [the European Medicines Agency] treats biobetters as biosimilars and allows applications for approval to follow a 'hybrid pathway’ based on data showing similar efficacy to the reference product, the FDA [the US regulatory authority] advises that drug applications are based on data from new clinical trials.”

Critics argue that a globally accepted, standardised set of regulatory guidelines would avoid duplicating clinical trials and allow medicines to come to market in a more timely fashion for the benefit of those patients who need them most. The lack of alignment also undermines confidence as patients rightly wonder why a drug is approved in Europe, for example, but not elsewhere.

While there is much potential for the biobetters market, the barriers to swift therapeutic access are challenging, not just when it comes to regulatory approval but also pricing.

“In terms of regulation of biobetters, the EMA provides an efficient regulatory track, but the pricing and reimbursement [P&R] processes also differ on a country-by-country basis,” says Dr Kim. “If there were a common or uniform P&R process shared by EU member states in the future, we believe this would facilitate commercialisation of these types of innovative products and would mean patients receive greater access to innovative treatments sooner.”

As the biopharmaceutical industry evolves, it needs to work hard to make its case for a seismic regulatory shift. Meanwhile, biopharma must continue its efforts to focus on patient centric innovation and deliver on the promise of its new products to change treatments and patients’ lives for the better.

This article was originally published in FT.com on December 14, 2021.

For more information on Sheba Medical Center's treatments and breakthroughs visit shebaonline.org.

Disclaimer : This content was paid for by Celltrion Healthcare and produced in partnership with the Financial Times Commercial department.