Follow-on Biologics Versus Line Extensions, and What Are the Implications for Biosimilars?

Is a citrate-free formulation of Humira®, which is supposed to result in less injection-site pain, just another part of the patent thicket, or is it a real-improvement in the brand? Payers aren’t impressed, based on discussions we had at the Academy of Managed Care Pharmacy (AMCP) annual meeting last week.

In her presentation, Jennifer Day, PharmD, Coordinator Emerging Therapeutics Strategy Program, Kaiser Permanente Drug Information Services offered that these products, and potential follow-on biologic products like ravulizumab (Ultomiris®), may create new barriers for biosimilar development and uptake.

According to several pharmacy directors and medical directors I spoke to in private conversations, they are approaching citrate-free Humira in the same way as they view Herceptin Hylecta® and Rituxan Hycela®, subcutaneous formulations of Roche’s two maintstay biologics for the treatment of cancer. They are more line extensions than follow-on biologics, and as such do not necessarily provide any additional value.

This is not to say that Roche’s products cannot produce some type of savings (either based on site of care or lower administration costs). The cancer chemotherapies would likely still be administered in a doctor’s office or clinic, they agreed, but faster administration time could result in lower fees. This doesn’t necessarily tip the scales in favor of the newer products, particularly if a biosimilar is available in the original formulations at lower costs. Yet, the subcutaneous formulations may make a stronger case for these oncology medications to be managed under the payer’s pharmacy benefit, with distribution via specialty pharmacy.

The payers are not placing significant value on the citrate-free version of adalimumab, partly because injection site pain is a lesser concern for them. Although it may be attractive to patients, payers are wary of ascribing any added value to this agent. If adalimumab biosimilars were available today as alternatives in the United States, based on what we are hearing, the citrate-free formulation would not prevent a run to lower-cost biosimilars.

The greater issue may be follow-on biologics like Ultomiris, which is being sold by the manufacturer of eculizumab (Soliris®). Eculizumab may be among the next generation of biologics targeted by biosimilar manufacturers. It was approved in 2007 by the Food and Drug Administration (FDA), and its utilization can be preempted by Alexion’s push to use the newer agent. At least one prospective manufacturer (Amgen) is working on a biosimilar agent for eculizumab.

It would be logical to expect that the threat of biosimilar activity could accelerate the development of follow-on agents, particularly in view of the success that biosimilar manufacturers have had in obtaining FDA approval. If the extraordinary patent defenses erected by some manufacturers, like AbbVie, are under continuing attack, accelerated development and marketing of a follow-on agent may be the next best action.

In related biosimilar news…Several disparate organizations are joining the front against AbbVie’s patent thicket strategy for Humira. Fierce Pharma is reporting that since the initial lawsuit by a union of New York grocery store workers last month, others like another union in New York of heavy machine operators, the police department of Miami, the mayor’s office in Baltimore, and Minnesota pipe fitters and electrical workers groups have filed class action lawsuits. The AbbVie lawsuit by police organization also implicated Amgen, in signing a pay-for-delay deal allowed it an effective 180 days of exclusivity where none was statutorily allowed.