Delving into the Latest Updates on Recombinant alkaline phosphatase(AM-Pharma Holding BV) with Synapse

Overview

Basic Info

Drug Type

Enzyme

Synonyms

Human recombinant alkaline phosphatase, recAP, Recombinant alkaline phosphatase

+ [1]

Target-

Mechanism-

Therapeutic Areas

Infectious DiseasesUrogenital DiseasesOther Diseases

Active Indication-

Inactive Indication

Acute Kidney InjurySepsis

Originator Organization

AM-Pharma Holding BV

Active Organization-

Inactive Organization

AM-Pharma Holding BV

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Ilofotase alfa is a human recombinant alkaline phosphatase with reno-protective effects that showed improved survival and reduced Major Adverse Kidney Events by 90 days (MAKE90) in sepsis-associated acute kidney injury (SA-AKI) patients. REVIVAL, was a phase-3 trial conducted to confirm its efficacy and safety.

METHODS:

In this international double-blinded randomized-controlled trial, SA-AKI patients were enrolled < 72 h on vasopressor and < 24 h of AKI. The primary endpoint was 28-day all-cause mortality. The main secondary endpoint was MAKE90, other secondary endpoints were (i) days alive and free of organ support through day 28, (ii) days alive and out of the intensive care unit (ICU) through day 28, and (iii) time to death through day 90. Prior to unblinding, the statistical analysis plan was amended, including an updated MAKE90 definition.

RESULTS:

Six hundred fifty patients were treated and analyzed for safety; and 649 for efficacy data (ilofotase alfa n = 330; placebo n = 319). The observed mortality rates in the ilofotase alfa and placebo groups were 27.9% and 27.9% at 28 days, and 33.9% and 34.8% at 90 days. The trial was stopped for futility on the primary endpoint. The observed proportion of patients with MAKE90A and MAKE90B were 56.7% and 37.4% in the ilofotase alfa group vs. 64.6% and 42.8% in the placebo group. Median [interquartile range (IQR)] days alive and free of organ support were 17 [0-24] and 14 [0-24], number of days alive and discharged from the ICU through day 28 were 15 [0-22] and 10 [0-22] in the ilofotase alfa and placebo groups, respectively. Adverse events were reported in 67.9% and 75% patients in the ilofotase and placebo group.

CONCLUSION:

Among critically ill patients with SA-AKI, ilofotase alfa did not improve day 28 survival. There may, however, be reduced MAKE90 events. No safety concerns were identified.

14 Mar 2022·Cureus

Not Your Typical Bisphosphonate Intolerance: A Case of Unusual Bone Pain With Low Alkaline Phosphatase

Author: Bickford, Brant W ; Bennett, Sonia ; Markert, Ronald J

Bisphosphonates, first-line medications for osteoporosis, are often not tolerated or discontinued for multiple reasons. Hypophosphatasia (HPP) is a genetic deficiency with the enzyme activity of tissue-nonspecific alkaline phosphatase (TNSALP). The symptoms of adult HPP are often non-specific, and the diagnosis may be delayed for years. Low serum alkaline phosphatase, a hallmark feature of HPP, is often overlooked. Genetic testing is recommended to confirm diagnosis, and treatment with asfotase alfa, a recombinant alkaline phosphatase, is available for patients with HPP. We report a case of HPP in a 71-year-old female with recurrent skeletal pain and bisphosphonate intolerance who ultimately was diagnosed with HPP.

01 Jan 2020·Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology

Clinical Practice Guidelines for Hypophosphatasia*

Article

Author: Kubota, Takuo ; Kitaoka, Taichi ; Namba, Noriyuki ; Mochizuki, Hiroshi ; Sawai, Hideaki ; Ozono, Keiichi ; Adachi, Masanori ; Ohata, Yasuhisa ; Fujiwara, Ikuma ; Michigami, Toshimi ; Fujiwara, Makoto ; Hasegawa, Kosei

Hypophosphatasia (HPP) is a rare bone disease caused by inactivating mutations in the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase (TNSALP). Patients with HPP have varied clinical manifestations and are classified based on the age of onset and severity. Recently, enzyme replacement therapy using bone-targeted recombinant alkaline phosphatase (ALP) has been developed, leading to improvement in the prognosis of patients with life-threatening HPP. Considering these recent advances, clinical practice guidelines have been generated to provide physicians with guides for standard medical care for HPP and to support their clinical decisions. A task force was convened for this purpose, and twenty-one clinical questions (CQs) were formulated, addressing the issues of clinical manifestations and diagnosis (7 CQs) and those of management and treatment (14 CQs). A systematic literature search was conducted using PubMed/MEDLINE, and evidence-based recommendations were developed. The guidelines have been modified according to the evaluations and suggestions from the Clinical Guideline Committee of The Japanese Society for Pediatric Endocrinology (JSPE) and public comments obtained from the members of the JSPE and a Japanese HPP patient group, and then approved by the Board of Councils of the JSPE. We anticipate that the guidelines will be revised regularly and updated.

100 Deals associated with Recombinant alkaline phosphatase(AM-Pharma Holding BV)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Kidney Injury	Phase 2	US	AM-Pharma Holding BV	18 Dec 2014
Acute Kidney Injury	Phase 2	AT	AM-Pharma Holding BV	18 Dec 2014
Acute Kidney Injury	Phase 2	BE	AM-Pharma Holding BV	18 Dec 2014
Acute Kidney Injury	Phase 2	CZ	AM-Pharma Holding BV	18 Dec 2014
Acute Kidney Injury	Phase 2	FI	AM-Pharma Holding BV	18 Dec 2014
Acute Kidney Injury	Phase 2	FR	AM-Pharma Holding BV	18 Dec 2014
Acute Kidney Injury	Phase 2	DE	AM-Pharma Holding BV	18 Dec 2014
Acute Kidney Injury	Phase 2	IE	AM-Pharma Holding BV	18 Dec 2014
Acute Kidney Injury	Phase 2	NL	AM-Pharma Holding BV	18 Dec 2014
Acute Kidney Injury	Phase 2	ES	AM-Pharma Holding BV	18 Dec 2014

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02182440 (STOP-AKI, CTgov)	Phase 2	Acute Kidney Injury \| Sepsis	301	Placebo (Placebo)	sbnzestpru(fwjyjpwrzk) = zouldjhxxa qcvyrqjzjn (tldulvmtqs, nscbfltflo - xgyjqxavgh) View more	-	23 Mar 2020
				recAP (0.4 mg/kg (250 U/kg) recAP)	sbnzestpru(fwjyjpwrzk) = xmihspihar qcvyrqjzjn (tldulvmtqs, yrgmshxglc - sjhpsfapsh) View more
ASN2014	Phase 2	-	-	Human recombinant Alkaline Phosphatase	mrkvsjlthi(mjdsmsauty) = eqxhsmkklb yjdcmnfruv (uowsxrievl ) View more	Positive	11 Nov 2014
				Placebo	mrkvsjlthi(mjdsmsauty) = wwvmfbrzpb yjdcmnfruv (uowsxrievl ) View more