CLINICAL DEVELOPMENT IN ONCOLOGY
AbbVie’s blockbuster Humira is any indication, the biosimilars could offer major discounts. For context, one dose of Keytruda, administered once every three weeks, is priced at $10,897.12, making any biosimilars an attractive option. Still, Roche has not released the list price
for Tecentriq SC. The spokesperson says, “The price of Tecentriq SC will vary from country to country.” The spokesperson adds the price will be “in parity with the price of the IV formulation”, but offer budget savings due to reduced administration time indirectly through shorter times on the infusion chair and for drug preparation.
Not easy to develop a subcutaneous formulation For a subcutaneous formulation to be effective, a high dose of the drug needs to be delivered within a relatively low volume. Conventional SC autoinjectors hold 2ml of liquid. Hackman likens the challenges behind developing a subcutaneous drug as taking a very potent intravenous formulation and trying to “squish it down into a very small syringe. These antibodies can all stick together creating viscosity or thickness of the formulation. And the challenge is how do you lower that viscosity, the glue-like effect that these antibodies have.” To develop Tecentriq SC, Roche employed
Halozyme Therapeutics’ Enhanze drug delivery technology, which uses recombinant human hyaluronidase PH20 (rH uPH20)
enzyme to stabilise the subcutaneous formulation. But other substances can also be used. Comera Life Sciences recently published a study demonstrating the use of caffeine to stabilise the subcutaneous antibody formulation of Bristol Myers Squibb’s Yervoy (ipilimumab). Fostering a partnership with companies like
Halozyme and Comera to develop SC versions may offer benefits. Hackman says these allow antibody companies to tap into specialist teams with experience in developing subcutaneous formulations, and proven platforms. That expertise goes a long way. “When you look at an antibody that comes in from a partnership, or one that we’re looking at for our own pipeline, we’re able to establish before we even get it into our lab, potentially how it might react to viscosity reduction, based on our platform, and the work we’ve done so far.” However, he cautions that “not every
intravenous formulation can move in this direction. So, the key is going to be finding those intravenous formulations that have the ability [to be formulated into subcutaneous versions].”
“Experience shows that [subcutaneous versions] can cannibalize a significant share of their IV counterparts”
32 | Clinical Trials in Oncology
Future events in the field After development, a subcutaneous formulation still needs to be tested separately. Hackman notes that, while developing a subcutaneous version, the potency of the drug and the way it is delivered is changed, which necessitates a comparability analysis to ensure that the drug is still safe and effective to use. The Tecentriq SC approval was based on the Phase Ib/III study (NCT03735121) demonstrating non-inferiority of the subcutaneous formulation compared to the intravenous. As a result, it has also been approved by the FDA as of September 2024. Merck and Bristol Myers Squibb are also
developing SC formulations for Keytruda and Opdivo, respectively. The race to launch these subcutaneous
formulations is on. Although Merck was able to dominate the market with Keytruda’s first-line approval, Roche just might buck the trend with Tecentriq SC’s first-to- market advantage.
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