A Pill to Replace the Needle: The Quest for an Oral Hypoparathyroidism Drug

MIAMI and TEL AVIV, Israel – February 04, 2026 – A groundbreaking partnership is accelerating the development of what could be a life-changing treatment for tens of thousands of patients: a once-daily pill for the rare endocrine disorder hypoparathyroidism. OPKO Health and Entera Bio announced today an expansion of their collaboration to fast-track a first-in-class oral long-acting parathyroid hormone (LA-PTH) tablet, aiming to file an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) by late 2026.

This move signals a significant push to replace the burdensome injections that currently define treatment for many with this chronic condition, potentially heralding a new era of patient-centric therapy.

A New Hope Beyond the Needle

For the approximately 70,000 to 100,000 people in the United States living with hypoparathyroidism, life is a constant balancing act. The disorder, caused by insufficient parathyroid hormone, leads to dangerously low calcium and high phosphate levels in the blood. For decades, the standard of care has been a demanding regimen of daily calcium and vitamin D supplements, which only manage symptoms and can lead to severe long-term complications, including kidney damage.

The advent of injectable PTH replacement therapies offered a more physiological approach. However, these treatments come with their own set of challenges. Ascendis Pharma’s Yorvipath, the only FDA-approved PTH replacement, requires patients to administer daily subcutaneous injections. While a major step forward, the reliance on needles remains a significant burden, impacting patient quality of life and adherence.

The initiative by OPKO and Entera aims to leapfrog the current standard of care entirely. An effective, once-daily oral tablet would eliminate the need for injections, freeing patients from a major source of treatment-related stress and inconvenience. Preclinical data from the collaboration suggests this is not a distant dream, indicating the potential for a single daily tablet at a significantly lower dose than previous oral PTH attempts, transforming the therapeutic landscape for this rare disease.

The Science of an 'Impossible' Pill

Delivering large-molecule drugs like peptides and proteins orally has long been considered one of the holy grails of pharmaceutical science. The harsh environment of the digestive system typically destroys these delicate molecules before they can be absorbed into the bloodstream. This is the challenge that Entera Bio’s proprietary N-Tab® technology was designed to solve.

The N-Tab® platform is a sophisticated oral delivery system that works in two key stages. First, an enteric coating on the tablet protects the PTH peptide from the corrosive acid of the stomach, ensuring it reaches the small intestine intact. Once there, the tablet releases its payload along with a protease inhibitor that shields the peptide from being broken down by digestive enzymes. Simultaneously, specialized absorption enhancers in the formulation facilitate the peptide's passage across the intestinal wall and into circulation. Entera has already demonstrated proof-of-concept for this platform in a Phase 2 study of an oral PTH for osteoporosis, which met its primary endpoints.

This innovative delivery system is now being combined with OPKO Health’s distinct expertise in protein chemistry. OPKO specializes in developing long-acting versions of therapeutic proteins, which extend their half-life in the body and reduce the frequency of dosing. By applying its technology to create a long-acting PTH variant, OPKO provides the ideal molecule for Entera's platform. The result is a synergistic combination: a long-lasting hormone that is protected and effectively delivered in a simple pill form.

A Synergistic Blueprint for Biotech

The expanded agreement between the two companies is a textbook example of modern biotech strategy, where collaboration and specialization accelerate innovation. Under the new terms, OPKO and Entera will share 50/50 pro-rata ownership and development costs for the oral LA-PTH program. This shared-risk, shared-reward model allows the clinical-stage Entera to pursue a capital-intensive program with the backing of a larger, established partner, while OPKO gains access to a potentially disruptive technology that complements its own R&D focus.

This LA-PTH program marks the third successful combination of the companies’ respective technologies, following promising work on oral GLP-2 and an oral dual GLP-1/glucagon agonist (oxyntomodulin). The continued success of the partnership underscores a deep strategic alignment. Further cementing this bond, Steve Rubin, an Executive Vice President at OPKO, will join Entera’s board of directors, bringing decades of drug development and corporate governance experience.

"The partnership that our team has forged with OPKO since late 2023 has been very synergistic," said Miranda Toledano, Chief Executive Officer of Entera. "Oral OXM and oral GLP-2 have both demonstrated robust PK profiles and bioavailability. Furthermore, preclinical data of oral LA-PTH suggests that this program holds the potential to transform the hypoparathyroidism landscape.”

Charting the Path Forward

With an accelerated timeline targeting an IND submission in late 2026, both companies are signaling strong confidence in their preclinical results and collaborative engine. The path to market for a novel oral biologic is complex, but the program may benefit from regulatory incentives such as Orphan Drug Designation, which is granted to therapies for rare diseases and can help streamline development.

Phillip Frost, M.D., Chairman and Chief Executive Officer of OPKO Health, remarked on the collaboration's promise. "We are pleased to expand our successful collaboration with Entera to advance this promising long-acting PTH program for hypoparathyroidism," he stated. "Our goal is to provide patients with hypoparathyroidism a more convenient treatment option that eliminates the burden of daily injections while maintaining therapeutic efficacy."

Beyond hypoparathyroidism, the partnership continues to advance other high-potential oral therapies. The companies are moving an oral oxyntomodulin, a dual-action peptide for obesity and metabolic disorders, into the clinic. Phase 1 data from an injectable version of this molecule is expected by the end of 2026, which will inform the subsequent development of the oral tablet formulation. This multi-program collaboration demonstrates a powerful model for leveraging complementary strengths to tackle some of healthcare’s most persistent challenges.