Preliminary Six-Month Data from Open-Label Extension of Phase 2 PaTH Forward Trial of TransConTM PTH in Adult Hypoparathyroidism Has Been Announced Recently

2020-04-26

- Six-month data from PaTH Forward open-label extension support potential use of TransConTM PTH as a hormone replacement therapy for adult hypoparathyroidism –

TransConTM PTH is an investigational long-acting prodrug of parathyroid hormone (PTH) in development as a once-daily hormone replacement therapy for adult hypoparathyroidism designed to replace PTH at physiologic levels for 24 hours each day and addresses both short-term symptoms and long-term complications of HP. Fifty-nine subjects participated in the phase 2 PaTH Forward Trial and continued in the OLE, where they all received a customized maintenance dose of TransConTM PTH (6 to 30 µg) with a ready-to-use, room temperature, prefilled pen injector. One subject randomized to placebo withdrew after completing the four-week double-blinded fixed-dose period for reasons unrelated to safety or efficacy of the study drug. All of the other 58 subjects remained on TransConTM PTH at the time of the six month data cutoff.

Preliminary OLE Results of PaTH Forward Trial at 6 Months

Preliminary six-month results from the PaTH Forward OLE demonstrated:

  • 91 percent of all subjects eliminated standard of care (defined as (1) off active vitamin D and (2) ≤500 mg per day of calcium supplements), including 76 percent who eliminated all supplements.

  • 86 percent of all subjects normalized or reduced by 50 percent 24-hour urine calcium.

  • 71 percent of all subjects achieved a response on the composite endpoint of (1) serum calcium in the normal range, (2) independence from active vitamin D, (3) taking ≤500 mg/day of calcium supplements, and (4) 24-hour urine calcium in the normal range or 50 percent reduction from baseline, including 74 percent of subjects who were randomized to TransConTM PTH.

  • All mean summary and subdomain SF-36® Health Survey scores normalized despite all mean scores starting below norms at baseline including subjects randomized to placebo who switched to TransConTM PTH group at week 4. Importantly, subjects randomized to TransConTM PTH demonstrated continued improvements from week 4 to month 6.

  • All doses of TransConTM PTH were well-tolerated, and no treatment-related serious or severe adverse events were observed at any point. No subjects had PTH treatment-emergent adverse events related to hyper- or hypocalcemia leading to emergency visit, urgent care visit, or hospitalization.

  • Adherence to daily injections of TransConTM PTH was 99.7 percent.

VISEN Pharma is responsible for  developing and commercializing TransConTM PTH through multiple license agreements in Greater China. We are now preparing an application for the communication meeting for the clinical plan in China to provide access to this treatment solution as quickly as is safe and feasible, bringing more benefits for Chinese patients.

About the PaTH Forward Trial

PaTH Forward is a global, phase 2, randomized, double-blind, placebo-controlled group trial evaluating the safety and efficacy of three fixed doses of TransConTM PTH (15, 18 or 21 µg/day or placebo). The trial enrolled 59 adult subjects with chronic HP who received standard of care or were previously treated with PTH therapies. The goal of PaTH Forward is to evaluate TransConTM PTH control of serum and urinary calcium and identify a titration regimen for complete withdrawal of standard of care (i.e., active vitamin D and calcium supplements). PaTH Forward has introduced a ready-to-use pre-filled pen injector and assesses disease-specific patient-reported outcomes. After four weeks of fixed dosing, all subjects were eligible to enter an open-label extension period with the opportunity to receive a customized maintenance dose of TransConTM PTH to evaluate long-term safety and efficacy.

About TransConTM PTH

TransConTM PTH is an investigational once-daily long-acting prodrug of parathyroid hormone (PTH[1-34]) in development as a treatment for adult hypoparathyroidism (HP) designed to replace PTH at physiologic levels for 24 hours each day to address both the short-term symptoms and long-term complications of the disease. TransConTM PTH was granted Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA) in June 2018.

About Hypoparathyroidism (HP)

Hypoparathyroidism (HP) is a rare endocrine disorder characterized by insufficient levels of parathyroid hormone (PTH), resulting in low calcium and elevated phosphate levels in the blood. HP affects approximately 200,000 patients in the United States, Europe, Japan and South Korea, the majority of whom develop the condition following damage or accidental removal of the parathyroid glands during thyroid surgery. Patients often experience decreased quality of life. In the short term, symptoms include weakness, severe muscle cramps (tetany), abnormal sensations such as tingling, burning and numbness (paresthesia), memory loss, impaired judgment and headache. Over the long term, this complex disorder can increase risk of major complications, such as extraskeletal calcium depositions occurring within the brain, lens of the eye, and kidneys, which can lead to impaired renal function.

HP remains among the few hormonal insufficiency states without a replacement therapy that restores the missing hormone at physiologic levels. Standard of care with active vitamin D analogs and calcium supplementation do not fully control the disease and may contribute to risk of renal disease. As a result, patients with HP have an estimated 4-fold to 8-fold greater risk of renal disease compared to healthy controls.

About TransConTM Technology

TransConTM refers to “transient conjugation.” The proprietary TransConTM platform is an innovative technology to create new therapies that are designed to potentially optimize therapeutic effect, including efficacy, safety and dosing frequency. TransConTM molecules have three components: an unmodified parent drug, an inert carrier that protects it, and a linker that temporarily binds the two. When bound, the carrier inactivates and shields the parent drug from clearance. When injected into the body, physiologic conditions (e.g., pH and temperature) initiate the release of the active, unmodified parent drug in a predictable manner. Because the parent drug is unmodified, its original mode of action is expected to be maintained. TransConTM technology can be applied broadly to a protein, peptide or small molecule in multiple therapeutic areas, and can be used systemically or locally.