Sara Lubitz, MD

The Future of Hypoparathyroidism Care: Research Priorities, Emerging Therapies, and Clinical Adoption of PTH Replacement

Looking ahead, the field of chronic hypoparathyroidism is on the cusp of broader adoption of PTH replacement and continued therapeutic innovation. In this final segment of the HCPLive Special Report, Sara Lubitz, MD, shares her vision for the next 5 to 10 years, beginning with a call to expand evidence for agents such as palopegteriparatide in populations that are currently understudied.

These include children and adolescents, as well as individuals who are pregnant or breastfeeding, for whom data on safety and long-term outcomes remain limited. She also points to the need for clear best practices in patients managing both hypoparathyroidism and comorbid conditions such as osteoporosis.

Lubitz identifies several critical research priorities that will shape future practice. Long-term studies are needed to clarify the impact of sustained PTH therapy on kidney function, cardiovascular disease, cognitive outcomes, and fracture risk. An important unanswered question is the degree to which the morbidity observed in chronic hypoparathyroidism—whether related to the disease itself or decades of conventional therapy—can be reversed or prevented with earlier and more physiologic PTH replacement. These data will be key in refining treatment algorithms and counseling patients about the long-range benefits and risks of therapy.

Finally, Lubitz notes that the therapeutic pipeline for hypoparathyroidism is increasingly active, with emerging agents targeting the PTH receptor or enhancing endogenous PTH through diverse mechanisms. Development programs are exploring daily, weekly, and potentially monthly injectable options, as well as oral approaches that could further decrease treatment burden.

Lubitz expresses optimism that PTH replacement will become the conventional standard for managing chronic hypoparathyroidism, relegating high-dose calcium and active vitamin D monotherapy to a more limited role as the field continues to evolve.

Videos

Sara Lubitz, MD, outlines key research priorities, emerging PTH-axis therapies, and her expectation that hormone replacement will become the new standard of care in chronic hypoparathyroidism.



Implementing Palopegteriparatide in Practice: Transition Protocols, Monitoring, and Reproductive Counseling

Transitioning from conventional calcium and active vitamin D therapy to palopegteriparatide requires a structured approach and clear patient counseling. In this portion of the HCPLive Special Report, Sara Lubitz, MD, explains that while she views most individuals without endogenous PTH as potential candidates for PTH replacement, the initial dose-finding phase can be demanding. After adjustments in calcium, active vitamin D, or palopegteriparatide doses, patients typically require laboratory monitoring every 7 to 10 days, with more frequent testing if symptoms of hypo- or hypercalcemia occur.

Lubitz stresses the importance of setting expectations and aligning the timing of transition with the patient’s personal and professional circumstances. She advises clinicians to select periods when patients can reliably attend laboratory appointments and manage potential symptom fluctuations, and to avoid intervals surrounding major surgery, extensive travel, or other disruptive events.

Some patients may find that summer breaks or times of reduced work obligations are optimal for initiating therapy. In her experience, patients who complete this transition generally regard the short-term inconvenience as worthwhile, and they overwhelmingly prefer to remain on palopegteriparatide rather than return to conventional regimens.

Special populations, particularly women of childbearing age, require additional counseling. Lubitz notes that robust safety data for PTH analogs, including palopegteriparatide, during pregnancy and lactation are currently lacking. She recommends proactive discussions about reproductive planning and emphasizes that, at present, patients are typically transitioned back to conventional calcium and vitamin D therapy when a planned pregnancy is anticipated. Clear communication about these limitations and a shared decision-making framework are essential to balancing potential maternal and fetal risks with the benefits of continued PTH replacement.

Sara Lubitz, MD, offers practical advice on transitioning appropriate patients to palopegteriparatide, including the dose-finding phase, laboratory monitoring, and considerations for women of childbearing potential.


Who Benefits Most from PTH Therapy? Patient Selection, Goals of Care, and Renal Protection

Determining which patients with chronic hypoparathyroidism should receive PTH replacement is increasingly guided by expert consensus. In this segment of the HCPLive Special Report, Sara Lubitz, MD, highlights recommendations from the 2022 Second International Workshop on the Evaluation and Management of Hypoparathyroidism.

These guidelines consider patients inadequately controlled on conventional therapy—those with symptomatic hypocalcemia, hyperphosphatemia, renal insufficiency, hypercalciuria, or poor well-being—as candidates who may benefit from therapies such as palopegteriparatide. Additional triggers include a requirement for high doses of oral calcium (>2 g/day) or active vitamin D (>2 mcg/day), intolerance or nonadherence to multiple daily pills, and malabsorption syndromes.

Lubitz reviews 6 major goals of care for chronic hypoparathyroidism. First, clinicians should avoid the signs and symptoms of hypocalcemia, including overt manifestations such as tetany and seizures as well as more subtle complaints like fatigue and cognitive dysfunction. Second, serum calcium should be maintained within a narrow therapeutic range; historically, guidelines recommended aiming for the lower end of normal or slightly below to avoid toxicity on conventional therapy, whereas PTH replacement can often normalize calcium without driving hypercalciuria.

Additional objectives include maintaining the calcium-phosphate product below 55 to reduce extraskeletal calcifications, avoiding hypercalciuria, and preventing hypercalcemia. Lubitz argues that improvement in quality of life should be explicitly recognized as another primary treatment goal, even though it is less easily quantified in busy practice.

Beyond symptom control and serum targets, Lubitz emphasizes the potential of PTH therapy to mitigate renal complications and reduce treatment burden. She notes that in the PATHWAY trial, patients treated with palopegteriparatide experienced a sustained, clinically meaningful rise in estimated glomerular filtration rate and a durable decline in 24-hour urinary calcium to normal ranges.

Pill burden was also markedly reduced: patients who began with an average of 6.7 “hypopara pills” per day (calcium and related agents) decreased to approximately 0.5 pills per day over 26 weeks. For many individuals, this represents a reduction of six or more tablets daily, which can have a substantial impact on adherence, quality of life, and overall treatment satisfaction.

Sara Lubitz, MD, discusses guideline-based criteria for selecting patients for PTH therapy, treatment goals, and how palopegteriparatide may reduce renal complications and pill burden.

Palopegteriparatide Mechanism and Phase 3 Outcomes in Chronic Hypoparathyroidism

Palopegteriparatide represents a new generation of PTH analog therapy designed to overcome the pharmacokinetic limitations of earlier agents. In this portion of the HCPLive Special Report, Sara Lubitz, MD, describes palopegteriparatide as a prodrug of the N-terminal PTH(1–34) analog that is engineered to provide sustained activation of the PTH1 receptor.

The agent uses a TransCon linker to enable slow release of active PTH, resulting in a prolonged half-life of approximately 60 hours for the released hormone. This design allows for once-daily subcutaneous dosing while maintaining physiologic PTH exposure over a full 24-hour period.

Lubitz reviews key findings from the phase 3, double-blind, placebo-controlled PATHWAY trial and its long-term extension. During the initial 26-week blinded phase, approximately 68.9% of patients treated with palopegteriparatide achieved a composite endpoint of normal albumin-adjusted serum calcium without conventional therapy, compared with only 4.8% of those receiving placebo.

With continued treatment and dose titration into the open-label extension, efficacy remained robust, with roughly two-thirds of patients maintaining normal calcium levels and independence from active vitamin D and pharmacologic calcium at 78 weeks.

Longer-term data out to approximately 182 weeks further support the durability of treatment response. Lubitz notes that 96% of patients were independent from conventional therapy and 89% maintained normal albumin-adjusted serum calcium during extended follow-up. Importantly, renal parameters improved, with a clinically meaningful increase in estimated glomerular filtration rate and a sustained reduction of 24-hour urinary calcium from hypercalciuric to normal levels. Patients also reported significant improvements in disease-specific symptoms, vitality, mental clarity, and overall impact on daily life as early as week 12, with benefits persisting over 3 years.

Sara Lubitz, MD, explains how palopegteriparatide delivers sustained PTH1 receptor activation and reviews phase 3 data demonstrating durable biochemical control and improved renal and QoL outcomes.

Sara Lubitz, MD

Articles