Ascendis Pharma Bone Diseases A/s

Ascendis Pharma A/s

Mathias Krusch

Thomas Wegge

Kennett Sprogøe

Guillaume Maitro

Joachim Zettler

Felix Cleemann

David Brian Karpf

Lars Holten-Andersen

Harald Rau

Ulrich Hersel

Dirk Vetter

Tobias Voigt

Julia Baron

Nora Kaluza

Kennett SprogØe

The present invention relates to pharmaceutical compositions comprising a controlled-release PTH compound or a pharmaceutically acceptable salt, hydrate, or solvate thereof, for use in a method of treating, controlling, delaying or preventing a condition which can be treated, controlled, delayed or prevented with PTH, wherein the pharmaceutical composition comprising the controlled-release PTH compound is administered in accordance with a dosage regimen in which dose adjustment in response to hypocalcemia or hypercalcemia is performed in increments of no more than 25%.

Incremental dose finding in controlled-release PTH compounds

The invention provides a method of treating or controlling hypoparathyroidism in a human patient by administering to the human patient a pharmaceutical composition comprising a controlled-release PTH compound or a pharmaceutically acceptable salt thereof. The controlled-release PTH compound comprises a PTH moiety reversibly conjugated to a branched polyethylene glycol carrier. The composition is administered by subcutaneous injection no more frequently than once every 24 hours with a dosage of the controlled-release PTH compound that corresponds to no more than 70% of the molar equivalent dose of PTH 1-84 administered by subcutaneous injection at the same dosing frequency required to maintain a serum albumin-adjusted calcium level in serum of above 8.5 mg/dL over a 24 hour period.

Controlled-release PTH compound

The present invention relates to PTH prodrugs, pharmaceutical compositions comprising such PTH prodrugs and their uses.

PTH prodrugs

The present invention relates to a controlled-release parathyroid hormone (PTH) compound in which PTH(1-34) is reversibly conjugated to a branched polyethylene glycol. The invention further relates to a pharmaceutical composition of the compound. The compound or pharmaceutical composition is useful for treatment, control, delay or prevention of a condition that can be treated, controlled, delayed or prevented with PTH.

The present invention relates to a pharmaceutical composition comprising a PTH compound, wherein after subcutaneous administration the pharmacokinetic profile of the PTH compound exhibits a peak to trough ratio of less than 4 within one injection interval.

PTH compounds with low peak-to-trough ratios

The present invention relates to biodegradable polyethylene glycol based water-insoluble hydrogels comprising backbone moieties which are interconnected by hydrolytically degradable bonds, the backbone moieties further comprising reactive functional groups, wherein the water-insoluble hydrogel is further characterized in that the ratio between the time period for the complete degradation of the hydrogel by hydrolysis of the degradable bonds into water-soluble degradation products comprising one or more backbone moieties and the time period for the release of the first 10 mol-% of water-soluble degradation products comprising one or more backbone moieties based on the total amount of backbone moieties in the hydrogel is greater than 1 and equal to or less than 2. The invention further relates to conjugates of such hydrogels with ligands or ligating groups, prodrugs and pharmaceutical compositions as well as their use in a medicament.

Biodegradable polyethylene glycol based water-insoluble hydrogels

The present invention relates to a prodrug or a pharmaceutically acceptable salt thereof comprising a drug linker conjugate D-L, wherein an aromatic amine containing biologically active moiety is connected (bound) by an amido bound to a linker. The invention also relates to pharmaceutical compositions comprising said prodrugs and their use as medicaments.

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Hirschhorn, Germany

Mathias Krusch