PMID- 34585991
OWN - NLM
STAT- MEDLINE
DCOM- 20211108
LR  - 20220531
IS  - 1744-7593 (Electronic)
IS  - 1742-5247 (Linking)
VI  - 18
IP  - 11
DP  - 2021 Nov
TI  - Safety of recombinant human hyaluronidase PH20 for subcutaneous drug delivery.
PG  - 1673-1685
LID - 10.1080/17425247.2021.1981286 [doi]
AB  - INTRODUCTION: The glycosaminoglycan hyaluronan forms a gel-like substance, which 
      presents a barrier to bulk fluid flow in the subcutaneous (SC) space, limiting SC 
      drug delivery volume and administration rates. Recombinant human hyaluronidase 
      PH20 (rHuPH20) acts locally to temporarily remove this barrier, facilitating 
      rapid SC delivery of large volumes and/or high doses of sequentially or 
      co-administered therapeutics. AREAS COVERED: An extensive clinical and 
      post-marketing dataset of safety and immunogenicity of rHuPH20 in its current 
      applications with approved therapeutics demonstrates that rHuPH20 acts locally, 
      without measurable systemic absorption at the SC doses used in the approved 
      products, and is well tolerated in combination with several co-administered 
      therapeutic agents across diverse patient groups. The immunogenicity profile 
      demonstrates no adverse effects associated with treatment-emergent rHuPH20 
      antibody responses. Immunogenicity to monoclonal antibodies co-formulated with 
      rHuPH20 shows no clinical difference between SC and intravenous administration. 
      Safety assessments of patient subsets for special populations, including 
      children, elderly patients, and pregnant women, raise no additional safety 
      concerns. EXPERT OPINION: The benefits of SC administration for patients and 
      healthcare systems often outweigh those of intravenous administration, driving 
      future initiation of SC-only drug development programs. Injection devices 
      allowing large-volume SC administration could be facilitated by incorporating 
      co-formulated biologics containing rHuPH20.
FAU - Knowles, Stephen P
AU  - Knowles SP
AD  - Halozyme Therapeutics, Inc, San Diego, CA, USA.
FAU - Printz, Marie A
AU  - Printz MA
AD  - Halozyme Therapeutics, Inc, San Diego, CA, USA.
FAU - Kang, David W
AU  - Kang DW
AD  - Halozyme Therapeutics, Inc, San Diego, CA, USA.
FAU - LaBarre, Michael J
AU  - LaBarre MJ
AD  - Halozyme Therapeutics, Inc, San Diego, CA, USA.
FAU - Tannenbaum, Renee P
AU  - Tannenbaum RP
AD  - Halozyme Therapeutics, Inc, San Diego, CA, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210929
PL  - England
TA  - Expert Opin Drug Deliv
JT  - Expert opinion on drug delivery
JID - 101228421
RN  - 0 (Pharmaceutical Preparations)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.2.1.35 (Hyaluronoglucosaminidase)
SB  - IM
MH  - Aged
MH  - Child
MH  - Drug Delivery Systems
MH  - Female
MH  - Humans
MH  - *Hyaluronoglucosaminidase
MH  - Injections, Subcutaneous
MH  - *Pharmaceutical Preparations
MH  - Pregnancy
MH  - Recombinant Proteins
OTO - NOTNLM
OT  - Immunogenicity
OT  - monoclonal antibody
OT  - recombinant human hyaluronidase PH20
OT  - safety
OT  - subcutaneous injection
EDAT- 2021/09/30 06:00
MHDA- 2021/11/09 06:00
CRDT- 2021/09/29 12:15
PHST- 2021/09/30 06:00 [pubmed]
PHST- 2021/11/09 06:00 [medline]
PHST- 2021/09/29 12:15 [entrez]
AID - 10.1080/17425247.2021.1981286 [doi]
PST - ppublish
SO  - Expert Opin Drug Deliv. 2021 Nov;18(11):1673-1685. doi: 
      10.1080/17425247.2021.1981286. Epub 2021 Sep 29.