NPS Pharmaceuticals, Inc. (NASDAQ:NPSP), a biopharmaceutical company pioneering and delivering therapies that transform the lives of patients with rare diseases worldwide, today announced that the company has submitted its Biologic License Application (BLA) to the U.S. Food and Drug Administration (FDA) for Natpara ® (recombinant human parathyroid hormone 1-84, rhPTH(1-84)). Natpara is a bioengineered replacement for endogenous parathyroid hormone (PTH) that NPS has developed for the treatment of hypoparathyroidism, a rare endocrine disorder in which the body produces insufficient levels of parathyroid hormone, a principal regulatory of the body’s mineral homeostasis. “Submitting our BLA for Natpara is a significant step forward for NPS in our effort to bring the first replacement therapy to patients with hypoparathyroidism,” said Francois Nader, MD, president and chief executive officer of NPS Pharmaceuticals. “Hypoparathyroidism patients face a significant burden of disease given the multitude of physical, cognitive, and emotional symptoms associated with this disorder.” PTH plays a central role in a variety of critical physiological functions, including closely modulating serum calcium and phosphate, regulating renal excretion of calcium and phosphate, activating vitamin D, and maintaining normal bone turnover. In patients with hypoparathyroidism, insufficient levels of PTH lead to low serum calcium, high serum phosphate, increased urinary calcium excretion, and decreased urinary phosphorus excretion. PTH deficiency can also disrupt skeletal homeostasis, leading to bone abnormalities. In addition, patients with insufficient levels of PTH are unable to convert native vitamin D into its active state to properly absorb dietary calcium. Acute symptoms of hypoparathyroidism are largely due to hypocalcemia and include fatigue, muscle spasms and cramps, tingling, tetany, seizures, brain fog/mental lethargy, anxiety, and depression. In the absence of an approved parathyroid replacement therapy, the standard approach focuses on using high doses of calcium and active vitamin D to increase calcium levels in the blood and reduce the severity of hypocalcemic symptoms. However, balancing the administration of supplements is challenging due to calcium fluctuations and the long-term use of high doses of calcium and vitamin D may lead to serious complications, including long-term renal damage. In addition, because serum phosphate levels are elevated when PTH is missing, increasing serum calcium may lead to irreversible calcium-phosphate deposits in the kidneys, arteries or brain. Further, supplements do not correct the abnormal bone metabolism due to PTH deficiency or enable the activation of vitamin D.
Natpara is a bioengineered replica of human parathyroid hormone designed to replace the missing hormone, which is a practice used successfully in treating other classic endocrine disorders. The company’s clinical development program for Natpara includes 12 pharmacology studies, five efficacy and safety studies in hypoparathyroidism, and a supporting development program consisting of seven studies in osteoporosis. The pivotal Phase 3 study known as REPLACE, was a randomized, double-blind, placebo controlled study of 134 patients with hypoparathyroidism.The results from the REPLACE study were recently published in The Lancet Diabetes & Endocrinology. Key findings from the study are summarized below.
- Fifty-three percent 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 by the end of the treatment phase. In contrast, only 2 percent of the placebo group (P<0.001) met the primary endpoint.
- Among secondary endpoints, by Week 24, 43 percent (36/84) of patients treated with Natpara were able to achieve independence from active vitamin D therapy and required only 500 mg/day or less of oral calcium, as compared to five percent (2/37) of patients treated with placebo (p<0.0001).
- From baseline, patients treated with Natpara reduced their oral calcium dose by an average of 52 percent (P<0.001), whereas those treated with placebo increased their average dose by 6 percent.
- The between-group differences in the average decrease from baseline for prescribed doses of both calcium and active vitamin D were apparent from week three until week 24 (p<0.002). Despite the large reductions in oral calcium and active vitamin D doses, serum calcium remained at or above baseline levels for the Natpara-treated patients without increasing mean urinary calcium excretion.
- Mean serum phosphate concentrations were similar (at the upper limit of normal) for both Natpara and placebo at baseline, but fell within normal in the Natpara group upon treatment and remained lower than in the placebo group throughout treatment (P<0.003 at all time points).
- At week 24, mean serum phosphate levels (±SD) had decreased by 0.46 (0.80) mg/dL and 0.09 (0.66) mg/dL for the Natpara and placebo groups, respectively (P<0.001).
- Natpara also showed a reduced calcium-phosphate product and replicated another effect of endogenous PTH by maintaining the serum level of 1,25-dihydroxyvitamin D despite a statistically significant mean reduction in active vitamin D doses.
- The overall incidence of adverse events (AE) and percentage of patients with an AE was similar between placebo (100 percent) and Natpara (93 percent) groups. By study end, 93 percent (84/90) of patients in the Natpara group and 100 percent (44/44) in the placebo group had at least one adverse event. The most common AEs were nervous system, metabolism and nutrition, musculoskeletal and connective tissue, and gastrointestinal disorders. During the maintenance phase of the study (weeks 16–24), a smaller proportion of Natpara-treated patients reported clinical symptoms associated with hypocalcaemia than those in the placebo-treated group; however, the difference was not statistically significant. Serious adverse event (SAE) rates were also similar between the placebo-treated (9 percent) and Natpara-treated (11 percent) groups. Only one serious AE of hypercalcemia in the Natpara group was considered treatment-related, and did not lead to study discontinuation. Three of 90 (3 percent) patients in the Natpara group discontinued treatment due to an AE, but only one of these patients’ events were thought to be related to treatment.
The FDA has granted orphan drug status for Natpara for the treatment of hypoparathyroidism.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 hypoparathyroidism and submitted its marketing application to the U.S. Food and Drug Administration in October 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. Disclosure notice 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 not receive FDA approval 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.