For conventional drug manufacturers, standard lifecycle management considerations include extending patent life through development of new dosage forms, formulations of extended- or sustained-release versions, or even the “next-generation” molecule (e.g., Prilosec® vs. Nexium®).
For manufacturers of biologics, the tools at their disposal for extending patent life are a bit more limited. A change in dosage forms is likely, as are extended-release versions. They can still attempt to develop next-generation versions that are more effective or safer than the parent molecule, which would offer at least some protection against biosimilar competition. These offspring are considered “biobetters.” Unlike the term, this concept is not really new. In the past, agents like colony-stimulating factors have been “pegylated” to produce enhanced effects.
Let’s consider one example. Roche’s (Genentech’s) product obinutuzumab (Gazya®) was approved by the FDA. This agent is a CD20-receptor antibody that is similar to the original CD20 product rituximab (Rituxan®). There are differences, however. The molecular structures differ slightly. Roche believes that Gazya has more antibody-dependent cell-mediated cytoxicity than Rituxan. This may translate into improved progression-free survival. Gazya has only one of Rituxan’s 7 indications (chronic lymphocytic leukemia), so it will not be a strict replacement for Rituxan. Rituxan may be facing biosimilar competition by 2018, and it will indeed be interesting to see how payers will utilize another version of rituximab. This may also be dependent on the extrapolation of indications for the original product.
Roche made the decision to seek approval for Gazya through the supplemental biologics license application (BLA) pathway, and it will be able to take advantage of full exclusivity periods, and possibly premium pricing (at least until biosimilars arrive). That may well justify the cost of conducting the full clinical trial program required for BLA approval.
Others took the “follow-on biologic” route—in this case, the molecule is not considered substantially different. Teva filed for approval of Granix® (tbo-filgrastim) as a BLA, because at that time, the 351(k) pathway did not yet exist. As a result of its approval, Teva received the full market exclusivity benefits of an originator biologic even though it is truly a biosimilar version of filgrastim. Entering a competitive marketplace, Granix has eroded Neupogen®’s marketshare, but it is subject to biosimilar competition to Zarxio®, in addition to whatever future filgrastim agents are approved. That might make a follow-on biologic little more than a “me-too,” with limited lifecycle prospects.