In the evolving world of biologic therapies, a class of follow-on biologics—so-called "biobetters"—is emerging as a new category of products.
In the evolving world of biologic therapies, a class of follow-on biologics—so-called “biobetters”—is emerging as a new category of products that could compete with biosimilars for market share.
The term “biobetter” was coined, according to the Generics and Biosimilars Initiative, by G.V. Prasad, CEO of Dr Reddy’s Laboratories, while speaking at an industry conference in Mumbai, India, in 2007. While the term “biosimilar” is applied to a drug that has been demonstrated to be highly similar to its reference, with no clinically meaningful differences from the originator product, the term “biobetter” refers to a therapy that has resulted from intentionally altering a biologic product in order to improve its clinical effects, require less frequent administration, or enhance tolerability.
In a recent review, published in Biotechnology and Applied Biochemistry, Malgorzata Kesik-Brodacka, PhD, explains that biobetters of monoclonal antibodies may be created through pegylation (which may increase half-life of a therapy) or combination with a cytoxic agent (which may enhance efficacy).
Examples of biobetters include Roche’s ado-trastuzumab emtansine (Kadcyla). The therapy, an antibody—drug conjugate, is a biobetter of trastuzumab (Herceptin, also developed by Roche), that has been demonstrated to slow disease progression in patients with HER2-positive advanced cancer. Another such product is obinutuzumab (Gazyva), a biobetter of rituximab, which has a different method of action, has been demonstrated to be less immunogenic, and triggers greater cytotoxicity than rituximab.
While these 2 drugs have been demonstrated to have advantages over the innovator biologics on which they were modeled, the term “biobetter,” when applied to such therapies is largely a matter of marketing. While guidelines exist for demonstrating biosimilarity of molecules, no regulatory pathway exists to demonstrate that an altered biologic is “biobetter” than the innovator biologic.
The lack of a specific approval pathway for altered biologics presents an opportunity for product developers; altering an originator biologic will result in a therapy that must be addressed as a new product under existing regulatory pathways. Approval of a new drug may lead to patent protection and market exclusivity, and could be used to help defend a company’s market share against biosimilar competition for originator products that have lost—or are about to lose—patent protection. “Both biosimilars and biobetters are natural alternatives for the reference biopharmaceuticals and therefore compete for the same market,” writes Kesik-Brodacka.
However, according to Nicola Davies, MD, writing in The Pharma Letter, the increased costs associated with biobetters, especially relative to the savings offered by biosimilars, could have an effect on uptake: “Many payers are searching for the most affordable treatment option available, which raises the concern of whether they will allow access for biobetters that may cost much more than biosimilars.” Biobetters, says Davies, would have to demonstrate a significant clinical advantage over biosimilar therapies in order to “…flourish and even co-exist with biosimilars.”