New calcilytic agreement with GSK:
>>BEDMINSTER, N.J.--(BUSINESS WIRE)-- NPS Pharmaceuticals, Inc. (NASDAQ: NPSP - News), a specialty pharmaceutical company developing orphan therapeutics for rare gastrointestinal and endocrine disorders, today reported that it has entered into a new agreement with GlaxoSmithKline (GSK), that terminates and replaces a prior collaborative research and license agreement between NPS and GSK from 1993, which focused on the discovery and development of small molecule antagonists of the calcium receptor that increase secretion of parathyroid hormone (calcilytics).
As part of the new agreement, GSK will assign to NPS the investigational new drug filings for two calcilytic compounds, SB-423557 and SB-423562 (NPSP790 and NPSP795). Both compounds have been evaluated in preclinical animal studies and Phase 1 human studies. NPS believes calcilytics may have clinical application in treating rare disorders involving increased calcium receptor activity, such as autosomal dominant hypocalcemia with hypercalciuria (ADHH).
The new agreement expands the licensed field of research for ronacaleret, which was discovered under the 1993 agreement and studied as a treatment for osteoporosis in post-menopausal women, to allow GSK to pursue stem cell transplants, in addition to osteoporosis and other bone disorders. GSK will be responsible for all development, manufacturing and commercialization of ronacaleret. NPS will be entitled to development milestones and royalties on any future sales of ronacaleret. GSK will no longer have rights to other calcilytic compounds discovered or developed under the 1993 agreement.
“We are pleased that GSK has decided to evaluate ronacaleret in new indications,” said Francois Nader, MD, president and chief executive officer of NPS Pharmaceuticals. “We are particularly excited about the prospects of assessing the potential of NPSP790 and NPSP795 in ADHH. This deal aligns with our commitment to develop orphan therapeutics in areas of high unmet medical need and is complementary to our late-stage pipeline, which already includes a Phase 3 compound in development for the rare endocrine disorder hypoparathyroidism.”
About ADHH
ADHH is a rare endocrine disorder caused by a gain-of-function mutation in the calcium-sensing receptor gene. The enhanced calcium sensitivity of the receptor to extracellular calcium results in decreased parathyroid secretion, which leads to chronically low blood levels of calcium or hypocalcemia, and in the kidneys, there is a high urinary calcium excretion (hypercalciuria) despite hypocalcemia. Calcium plays a central role in the activity of many physiological systems, including the health and function of the skeletal, muscular, nervous, urinary, and cardiovascular systems. Raising the patient’s serum calcium concentrations with supplementation of calcium and active metabolites of vitamin D does not treat the underlying physiological defect and can worsen hypercalciuria. Chronic hypercalciuria carries the risks of nephrocalcinosis, nephrolithiasis, and renal impairment. There is currently no approved treatment for ADHH.
About Calcilytics
Calcilytics are small molecule antagonists of the calcium receptor. Initially developed to stimulate parathyroid hormone secretion and bone formation for the treatment of osteoporosis and other bone metabolism disorders, they have been shown to increase serum calcium and decrease urinary calcium excretion in a Phase 2 study of patients with osteoporosis. Calcilytics could be a novel treatment for disorders involving increased calcium receptor activity.<<
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So no money changes hands, the lead calcilytic gets another shot on goal -- but has to skate from its own end -- and NPSP gets to blow some money on some compounds GSK had been stuck with. Don't know anything about them, since GSK probably had the P! results under wraps. But I can dig a bit. Still holding pending decision on GATTEX.
Edit: Here's a vague abstract on the compounds:
>> Bone. 2010 Feb;46(2):534-42. Epub 2009 Sep 26.An orally active calcium-sensing receptor antagonist that transiently increases plasma concentrations of PTH and stimulates bone formation.
Kumar S, Matheny CJ, Hoffman SJ, Marquis RW, Schultz M, Liang X, Vasko JA, Stroup GB, Vaden VR, Haley H, Fox J, DelMar EG, Nemeth EF, Lago AM, Callahan JF, Bhatnagar P, Huffman WF, Gowen M, Yi B, Danoff TM, Fitzpatrick LA.
SourceGlaxoSmithKline, UM 2230, 709 Swedeland Road, King of Prussia, PA 19406-2711, USA.
AbstractDaily subcutaneous administration of exogenous parathyroid hormone (PTH) promotes bone formation in patients with osteoporosis. Here we describe two novel, short-acting calcium-sensing receptor antagonists (SB-423562 and its orally bioavailable precursor, SB-423557) that elicit transient PTH release from the parathyroid gland in several preclinical species and in humans. In an ovariectomized rat model of bone loss, daily oral administration of SB-423557 promoted bone formation and improved parameters of bone strength at lumbar spine, proximal tibia and midshaft femur. Chronic administration of SB-423557 did not increase parathyroid cell proliferation in rats. In healthy human volunteers, single doses of intravenous SB-423562 and oral SB-423557 elicited transient elevations of endogenous PTH concentrations in a profile similar to that observed with subcutaneously administered PTH. Both agents were well tolerated in humans. Transient increases in serum calcium, an expected effect of increased parathyroid hormone concentrations, were observed post-dose at the higher doses of SB-423557 studied. These data constitute an early proof of principle in humans and provide the basis for further development of this class of compound as a novel, orally administered bone-forming treatment for osteoporosis.<<
Obviously not in the indications NPSP is going to study, but if the goal is raising serum calcium while lowering its excretion, well, these drugs seem to do that.
Meanwhile, NVS is apparently still pursuing a calcilytic program for osteoporosis. But that's not an issue for NPSP unless NVS decides to go after the same small markets. If NPS gets orphan designation first, that would further discourage NVS.
Cheers, Tuck |
