Where Did The Biobetters Buzz Go?
By Anna Rose Welch, Editorial & Community Director, Advancing RNA
The past few weeks, it seems the word on everyone’s tongue — including my own — has been biosimilars. Since the approval of Novartis’ Zarzio in the U.S., there’s been a lot of discussion and speculation about how this important approval will affect current blockbusters on the market and who will enter the space next.
But I’m left with another question: What happened to the buzz over biobetters? A few years ago, it seemed biobetters were becoming a more promising alternative to drug developers than biosimilars. However, there’s been surprisingly little being written about them as of late, which has left me wondering: Have biobetters been beaten out by biosimilar development?
Biobetters Vs. Biosimilars
The Generics and Biosimilars Initiative Journal (GaBI Journal) defines the biobetter as a drug that is designed to go a step further than the biosimilar. Rather than designing a drug to closely resemble a reference product, those making biobetters seek to improve the clinical profile of a certain drug by altering the drug’s structure and/or improving its formulation. These changes can make a drug easier for patients to administer and can contribute to a longer half-life in the body.
Back in 2010, the Wall Street Journal published a blog post a few short months after congressional approval of the biosimilar regulatory pathway. Biosimilars were, like now, an alluring prospect. However, as the Journal says, some venture backed start-ups were setting their sights on the development of biobetters, rather than biosimilars.
Biobetters were appealing for several reasons, one being that the approval pathway for these drugs was already established. (They’re considered new molecules that must follow the traditional drug approval pathway.) Despite the fact that we now have an approved biosimilar pathway in the U.S., it still lacks clarity and has a ways to go before it is fully defined.
According to Chemical and Engineering News (CEN), those developing biobetters would also be more likely to see higher margins and be able to charge higher prices for these kinds of drugs. Not only could biobetters target a larger patient-base, they are also less likely to be replaced quickly by second-generation products, as a bisomilar could be.
However, despite these pros, there are some big cons — especially considering the industry’s overarching goals to cut down on the time and costs of drug development. According to CEN, biobetters might take even longer than the estimated seven to eight years it would take to create and prove a biosimilar’s similarity to its reference biologic. The cost of developing a biobetter is also estimated to come in over the $250 million earmarked for biosimilar development.
The increased time and financial costs have perks though — the longer and more costly the development, the more likely the drugs will be able to gain patent protection and be put on the market for a premium price rather than a discount, unlike biosimilars. (Given the hostile climate for increasing drug prices as of late, I’m going to take a wild guess that these “premium prices” wouldn’t be seen as a plus in the eyes of payers, however.)
Who Are The Current Biobetter Players — And Who Might Be?
Current players in the biobetters game include Eli Lilly, Merck, Roche, Sanofi, Biogen Idec, GSK, and Novo Nordisk, says BioPharma-Reporter.
One of the most recent and notable players in the space is that of Roche’s Gazyva. While some consider Gazyva to be a third generation mAb, the drug is also considered by some to be a biobetter in the treatment of chronic lymphocytic leukemia (CLL). According to Biopharma-Reporter, pharmaceutical consultant Saurabh Aggarwal deemed Gazyva the “Son of Rituxan”, which is a treatment in Biogen Idec’s portfolio that targets the antigen CD-20 in lymphomas, leukemias, and autoimmune diseases.
Gazyva, which also targets this antigen, was tweaked in development to allow greater antibody-dependent cell-mediated cytotoxicity (ADCC) than Rituxan. While the biobetter was only approved to treat CLL, Rituxan has several more lucrative indications under its belt besides CLL, including non-hodgkin’s lymphoma. Gazyva, which is currently being investigated in 17 other studies, could garner additional indications — a situation that would threaten those tackling biosmilar development for Rituxan, says Aggarwhal.
Apart from Gazyva in the CLL indication, new research from GlobalData showed that the growth hormone deficiency treatment therapeutic area lends itself well to biobetters. According to the research, the products currently in late-stage clinical trials in the U.S., Germany, France, U.K., and other major markets are biobetters, primarily because of the established regulatory pathway for these drugs, their higher price tags, and the fact that they offer an improved clinical profile and boost patient compliance.
While a high price tag can raise some eyebrows in the marketplace, Global Data analysts cite the fact that a GH biosimilar, which was being sold for cheaper, did not perform as well in the market because popular drugs in this particular market are often evaluated by their delivery options, patient assistance programs, and company rebates to payers.
The impressive line-up of big-names at work in the biobetter space shouldn’t surprise, given the fact that biobetters require larger clinical trials — a financial undertaking that can really only be tackled by larger companies. Given this fact, contract research organizations (CROs) could stand to gain more business from an increased interest in biobetter development.
In fact, biobetter development could lead to growth in the contract manufacturing space, as well. According to the 11th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production, contract manufacturing organizations (CMOs) are poised to contribute roughly 40 percent of the current biosimilar/biobetter pipeline.
Considering there are, in fact, several big companies at work in the biobetter’s space, it’s clear development of these drugs is still an important strategy to bolster pipelines and revenues — even though it seems they’ve been kept under the radar. Given the recent attention that’s been lavished on the high price of new drugs hitting the market today, it makes sense that the cost-saving potential of biosimilars makes for some good headlines.
But perhaps all the attention being turned to bisimilars is a good thing; if biobetters are actually a more secure and lucrative asset to have in the pipeline compared to biosimilars, perhaps a lack of pomp and circumstance could make these players the industry’s best kept secret.