BEDMINSTER, N.J.--(EON: Enhanced Online News)--NPS Pharmaceuticals, Inc. (NASDAQ:NPSP), a biopharmaceutical company pioneering and delivering therapies that transform the lives of patients with rare diseases worldwide, yesterday presented findings from the company’s pivotal Phase 3 study of Natpara® (recombinant human parathyroid hormone 1-84, rhPTH(1-84)), known as REPLACE, suggesting the investigational therapy has a beneficial effect on bone health in patients with hypoparathyroidism. Investigators also reported findings from the PARADOX burden of illness survey suggesting that patients with hypoparathyroidism have a substantial burden of illness in the skeleton and joints and experience bone-related symptoms and comorbidities despite receiving standard care, such as calcium and active vitamin D. Findings from REPLACE and PARADOX were presented in respective poster sessions at the Annual Meeting of the American Society for Bone and Mineral Research (ASBMR) in Baltimore, MD.
“Treatment with Natpara may restore bone remodeling in patients with hypoparathyroidism, as shown by improvements in a number of measures. The data support the notion that Natpara may have a direct benefit on bone health.”
“The new findings presented from the REPLACE study add to the growing body of clinical evidence demonstrating the effects of Natpara in the treatment of hypoparathyroidism, a rare endocrine disorder,” said lead study investigator, John P. Bilezikian, MD, professor of medicine, Division of Endocrinology, Columbia University College of Physicians and Surgeons. “Treatment with Natpara may restore bone remodeling in patients with hypoparathyroidism, as shown by improvements in a number of measures. The data support the notion that Natpara may have a direct benefit on bone health.”
Natpara is a bioengineered replica of human parathyroid hormone that is being developed by NPS for adults with hypoparathyroidism, a rare endocrine disorder that is characterized by insufficient levels of parathyroid hormone, a principal regulator of the body’s mineral homeostasis. Abnormal bone structure with high bone mineral density is a well-recognized consequence of hypoparathyroidism that is likely caused by decreased bone turnover in the absence of parathyroid hormone.
In a poster session, lead study investigator Dr. John P. Bilezikian and colleagues presented “Changes in Bone Turnover Markers and Bone Mineral Density With Recombinant Human Parathyroid Hormone, rhPTH(1-84), in Hypoparathyroidism: Potential Utility as Surrogate Endpoints for Monitoring – the REPLACE Study.” The presentation focused on the effects of Natpara on changes in bone turnover markers and bone mineral density after 24 weeks of treatment in REPLACE.
In the study, 53 percent (48/90) of Natpara-treated patients achieved the primary endpoint by decreasing doses of oral calcium and active vitamin D by 50 percent or more, while maintaining serum calcium levels between 7.5mg/dL and the upper limit of normal by the end of the treatment phase. In contrast, only 2 percent of the placebo group (P<0.001) met this endpoint.
At baseline, mean bone turnover markers (BTM) in both the Natpara and placebo groups were in the low-normal range. These measures increased to significantly higher levels from baseline to Week 24 in those treated with Natpara, regardless of whether patients met the primary endpoint (P<0.001 vs. placebo for all markers). Increased remodeling in all Natpara-treated patients demonstrates a potential benefit of Natpara on bone health. No change in BTMs was seen in the placebo group.
At baseline, mean levels of bone mineral density (BMD) were elevated in both Natpara-treated patients and placebo-treated patients. Improvements in BMD, defined as decreases from baseline, were seen for all patients treated with Natpara, regardless of whether patients met the primary endpoint. No changes or increases in BMD were observed in the placebo-treated patients.
The mean percentage change in BMD from baseline to Week 24 is summarized in the table below. BMD was measured by dual-energy x-ray absorptiometry at baseline and Week 24.
|Femoral Neck||- 2.686*||- 2.625*||+ 0.015|
|Total Hip||- 2.487*||- 1.553*||- 0.005|
|Lumbar Spine||- 1.011||- 0.598||+ 0.234|
|Distal 1/3 Radius||- 0.291||- 0.414||+ 0.251|
*denotes P<0.001 vs. baseline
Overall, in the REPLACE trial, flexible dosing of Natpara (50, 75 or 100µg/day subcutaneous injection) improved bone remodeling as shown by the increase in bone turnover markers and the reduction in bone mineral density while the patients treated with only calcium and active vitamin D had no such improvement.
Investigators also reported results from the PARADOX, the largest and most comprehensive research analyzing the burden of hypoparathyroidism, to date.
In a poster session, lead study investigator Dr. Bart L. Clarke and colleagues presented “Bone-Related Complications Reported Among Patients With Hypoparathyroidism: Patients’ Attitudes and Responses About Hypoparathyroidism Toleration Explored (PARADOX) Study.” The presentation focused on bone-related complications reported by patients surveyed in PARADOX and the objective of the analysis was to assess bone-related symptoms and comorbidities experienced by patients despite receiving standard management with calcium and active vitamin D.
Key findings from the analysis demonstrate that 67% (251/374) of patients reporting joint or bone pain and female patients were significantly more likely to report joint or bone pain than male patients (70% vs. 50%; P≤0.05). Patients with severe disease were more likely than patients with mild or moderate disease to experience joint or bone pain multiple times per day and to report severe joint or bone pain (P≤0.05 for each comparison between disease severity groups).
Investigators concluded that patients with hypoparathyroidism have a substantial burden of illness in the skeleton and joints with two-thirds of the patients reporting joint or bone pain despite receiving standard management with calcium and active vitamin D.
NPS expects to submit its Biologics License Application to the U.S. Food and Drug Administration (FDA) for the treatment of hypoparathyroidism in the fourth quarter of 2013. The U.S. prevalence of hypoparathyroidism is estimated to be approximately 60,000 to 80,000.
REPLACE, a 24-week international phase 3 study of efficacy and safety of daily subcutaneous Natpara in 134 patients with hypoparathyroidism, is the largest randomized, placebo-controlled clinical trial conducted to date in patients with this rare and complex endocrine disorder. In the study, active vitamin D and calcium were progressively reduced, while Natpara could be titrated up from 50 to 75 or 100 µg. Prior to receiving treatment, patients were optimized to adjust their albumin-corrected serum calcium levels within a target range between 7.5 mg/dL and the upper limit of normal. Following the optimization period, patients were randomized 2:1 to 50 µg/day Natpara or placebo. Patients self-administered treatment for 24 weeks and were then followed for four additional weeks.
The PARADOX research assessed the clinical, social and economic implications of hypoparathyroidism in 374 patients in the U.S. aged 18 years or older who were diagnosed with the disorder for at least six months ago. The mean age of respondents was 49 years and a mean time with hypoparathyroidism of 13 years. Eight-five percent of respondents were female and 78% suffered with postsurgical hypoparathyroidism.
PARADOX was approved by an institutional review board, led by researchers from the Mayo Clinic, and conducted in conjunction with the Hypoparathyroidism Association. Data were collected through a 30-minute, web-based instrument which was developed with input from clinical experts, the Hypoparathyroidism Association, and patients. This instrument was primarily disseminated via email to Hypoparathyroidism Association members. Until now, there has been limited research exploring the impact of hypoparathyroidism on the lives of patients, and the nature, type and quantity of hypoparathyroidism symptoms have not been previously documented to this extent. NPS plans to present/publish additional findings from PARADOX at future medical meetings and in peer-reviewed publications.
About NPS Pharmaceuticals
NPS Pharmaceuticals is a biopharmaceutical company pioneering and delivering therapies that transform the lives of patients with rare diseases worldwide. The company’s lead product, Gattex® (U.S.)/Revestive® (EU) (teduglutide [rDNA origin]) for injection is approved for adult Short Bowel Syndrome (SBS) patients who are dependent on parenteral support. NPS has also developed Natpara® (rhPTH [1-84]) for the treatment of adult hypoparathyroidism and expects to submit its marketing application to the U.S. Food and Drug Administration in 2013.
NPS's earlier stage pipeline includes NPSP795, a calcilytic compound with potential application in rare disorders involving increased calcium receptor activity, such as autosomal dominant hypocalcemia (ADH). NPS complements its proprietary programs with a royalty-based portfolio of products and product candidates that includes agreements with Amgen, GlaxoSmithKline, Janssen Pharmaceuticals, and Kyowa Hakko Kirin. Additional information about NPS is available through its corporate website, http://www.npsp.com.
“NPS,” “NPS Pharmaceuticals,” “Gattex,” “Natpara,” “Revestive,” “Preotact,” and “NPS Advantage” are the company's trademarks. All other trademarks, trade names or service marks appearing in this press release are the property of their respective owners.
Statements made in this press release, which are not historical in nature, constitute forward-looking statements for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. These statements are based on the company's current expectations and beliefs and are subject to a number of factors and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Forward looking statements include, but are not limited to, statements concerning the company’s future financial performance. Risks associated to the company's business include, but are not limited to, the risks associated with any failure by the company to successfully commercialize Gattex (teduglutide [rDNA origin])for injection, including the risk that physicians and patients may not see the advantages of Gattex and may therefore be reluctant to utilize the product, the risk that private and public payers may be reluctant to cover or provide reimbursement for Gattex, the risk that the company will be unable to submit its BLA for Natpara, the risks associated with the company's strategy, global macroeconomic conditions, the impact of changes in management or staff levels, the effect of legislation effecting healthcare reform in the United States, as well as other risk factors described in the company's periodic filings with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K and Form 10-Qs. All information in this press release is as of the date of this release and NPS undertakes no duty to update this information, whether as a result of new information, future events or otherwise.