Tony Hagen is senior managing editor for The Center for Biosimilars®.
Product differentiation via oral formulations of biologics could be the next battleground between originators and biosimilar companies.
Oral technology for biologics seems poised to gather steam rapidly once it is demonstrated that pill formulations can succeed in patient therapy. A few recent surveys suggest that physicians in the field of rheumatology would lean toward use of pills over injections as a way to improve very high patient nonadherence rates.
According to a 2018 study, there are 10.2 million adults 50 years and older who have osteoporosis and another 43.4 million with low bone mass. Authors of the study said as many as half of patients recommended for osteoporosis therapy do not take their medication. Data were drawn from the PAADRN study of 7749 patients 50 years or older.
Many reasons for nonadherence were cited; however, use of syringes was not specifically noted as a top reason. Fear of adverse events or contraindications was reported most often by patients in the study (53.3%), followed by not liking to take medicines (25.3%) and doubts that the medicine would improve health (16.7%).
Potential Rapid Uptake
Despite these results, surveys have suggested that oral biologic formulations would be rapidly accepted by physicians if they become available. In 2018, Rani Therapeutics, in partnership with polling group Frost & Sullivan, touted results of a survey they said indicated pill formulations would help biosimilar companies achieve market share gains against makers of original biologics.
The survey comprised 500 patients and more than 100 physicians, including gastroenterologists and rheumatologists, and indicated 88% of patients and 86% of rheumatologists and gastroenterologists would switch from adalimumab injections to once-daily adalimumab pills should those become available.
The Humira originator version of adalimumab is not yet available in pill form; however, its maker, AbbVie, has since introduced the oral follow-on product Rinvoq (upadacitinib), a Janus kinase (JAK) inhibitor also for the treatment of rheumatoid arthritis. JAK inhibitors help to suppress cell signaling that leads to inflammation characteristic of rheumatic conditions.
Rinvoq was launched in the third quarter of 2019 and garnered $47 million in sales for that entire year, so the jury remains out whether this product can carry consumer demand away from Humira, which will lose exclusivity in the United States in 2023, at which time multiple biosimilar versions are expected to hit the market. Humira’s 2019 US sales were $14.9 billion.
The Frost & Sullivan survey found high estimates of adalimumab nonadherence. Sixty-two percent of patients reported they skip their injections or consistently fail to inject the drug as prescribed. Survey results also indicated 70% of rheumatologists and 92% of gastroenterologists anticipate that adherence would significantly improve via transitions from injection to pill delivery.
"What is clear from our research is that patients and physicians are overwhelmingly in favor of replacing a syringe with a pill,” said Charlie Whelan, director of consulting for Frost & Sullivan’s Healthcare & Life Sciences practice.
Additional Survey Findings
In July 2020, Entera Bio reported results of 2 market surveys of clinicians who treat patients with osteoporosis, one conducted among physicians in the United States, Canada, and Europe, and the other done in Japan. Entera Bio said the clinicians were overwhelmingly anticipating that an oral formulation of parathyroid hormone (PTH) for the treatment of moderate to severe osteoporosis would improve adherence and ease of administration.
“Due to the high cost, inconvenience, and pain associated with injectable osteoanabolic products, which are currently the standard of care for treating moderate to severe osteoporosis, it is estimated that only 5% of patients with severe osteoporosis actually receive treatment for their disease,” Entera CEO Adam Gridley said in a statement. “Remarkably, approximately 45% of the participating physicians indicated the oral PTH would be their first line treatment choice for their patients with severe osteoporosis.”
The survey in the United States, Canada, and Europe comprised mostly rheumatologists and endocrinologists, and 84% said they would be likely to prescribe oral PTH for osteoporosis; the equivalent percentage for Japanese survey participants, who comprised mostly orthopedists, was 89%.
Entera Bio has 2 product candidates in phase 2 clinical development: EB613 for the treatment of osteoporosis and EB612 for the treatment of hypoparathyroidism. The company is developing a carrier-molecule oral vehicle for biologics that binds the therapy to receptor-specific molecules that can penetrate the intestinal lining, providing passage and therapy delivery to the targeted area of the body.
“We believe the promising feedback from physicians currently involved in the care of high fracture risk patients with current osteoporosis medications may result in a rapid market adoption of the first oral PTH product,” Arthur Santora, chief medical officer of Entera Bio, said.