Delving into the Latest Updates on Pegvorhyaluronidase alfa with Synapse

Overview

Basic Info

Drug Type

Enzyme

Synonyms

Pegvorhyaluronidase alfa (USAN/INN), Pegylated hyaluronidase, Pegylated recombinant human hyaluronidase

+ [8]

Target

Hyaluronic acid

Action

modulators

Mechanism

Hyaluronic acid modulators

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication

Pancreatic adenocarcinoma metastaticProstatic Cancer

Inactive Indication

Advanced Malignant Solid NeoplasmAnophthalmia With Pulmonary HypoplasiaGallbladder adenocarcinoma+ [7]

Originator Organization

Halozyme Therapeutics, Inc.

Active Organization

Halozyme Therapeutics, Inc.

Inactive Organization

The University of California, San Francisco

License Organization

Nektar Therapeutics

Merck & Co., Inc.

Halozyme Therapeutics, Inc.

Drug Highest PhasePhase 1/2

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 136165

Source: *****

This study is the study of the combination of PEGPH20 and Pembrolizumab (MK-3475) for patients with previously treated Hyaluronan High (HA-high) metastatic pancreatic ductal adenocarcinoma. This study is an interventional, unblinded, open label study. Approximately 35 subjects will be enrolled. The trial will require approximately a total of 18 months, including 12 months for enrollment, with an additional 6 months for patient follow-up, data collection and study closure.
Each subject will participate in the trial from the time the subject signs the Informed Consent Form (ICF) through the final contact. After a screening phase of up to 21 days, eligible subjects will receive PEGPH20 beginning with Cycle 1 Day 1, on Days 1, 8 15 of every 3 week-cycles and pembrolizumab beginning on Cycle 1 Day 1 (2-4 hrs after PEGPH20), every 3-week-cycles.
Treatment with PEGPH20 and pembrolizumab will continue until progressive disease (PD), unacceptable adverse events (AEs), intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the subject, subject withdraws consent, pregnancy of the subject, noncompliance with trial treatment or procedure requirements, subject receives 35 treatments (approximately 24 months) of pembrolizumab, or administrative reasons requiring cessation of treatment. Subjects who discontinue for reasons other than PD will have post-treatment follow-up for disease status until PD, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. All subjects will be followed by telephone for overall survival (OS) until death, withdrawal of consent, or the end of the study.
After the end of treatment, each subject will be followed for 30 days for AE monitoring. Serious adverse events (SAE) and events of clinical interest (ECI) will be collected for 90 days after the end of treatment or for 30 days after the end of treatment if the subject initiates new anticancer therapy, whichever is earlier.

Start Date01 May 2019

Sponsor / Collaborator

Pancreatic Cancer Research Team

[+3]

100 Clinical Results associated with Pegvorhyaluronidase alfa

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100 Translational Medicine associated with Pegvorhyaluronidase alfa

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100 Patents (Medical) associated with Pegvorhyaluronidase alfa

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61

Literatures (Medical) associated with Pegvorhyaluronidase alfa

01 Apr 2025·Clinical Pharmacology & Therapeutics

Investigational Use of Real‐World Data as a Hybrid Control in Pancreatic Ductal Adenocarcinoma From the Randomized Phase Ib/II MORPHEUS Trial

Article

Author: Ponz‐Sarvise, Mariano ; Mhatre, Shivani K. ; Machado, Robson ; Bretscher, Michael T. ; Ci, Bo ; Zhu, Jiawen ; Lau, Janet ; Zhang, Xiaosong ; Li, Shi ; Oh, Do‐Youn ; Reyes‐Rivera, Irmarie ; Patel, Jilpa ; Ko, Andrew H. ; Psioda, Matthew A.

Enrolling adequate numbers of patients into the control arm of randomized controlled trials (RCTs) often presents barriers. There is interest in leveraging real‐world data (RWD) from electronic health records (EHRs) to construct external control (EC) arms to supplement RCT control arms and form hybrid control (HC) arms. This investigation showed the use of an HC arm in second‐line metastatic pancreatic ductal adenocarcinoma (PDAC). The RCT experimental arm (atezolizumab + PEGylated recombinant human hyaluronidase (Atezo + PEGPH20)) was compared with an HC arm consisting of patients treated with modified FOLFOX6 or gemcitabine/nab‐paclitaxel from the MORPHEUS PDAC internal control arm supplemented with data from a nationwide EHR‐derived de‐identified database as the EC arm. The EC arm was constructed by applying key inclusion/exclusion criteria from the MORPHEUS PDAC trial to patients from the real‐world cohort. Baseline variables were balanced using propensity score matching and covariate adjustment. Three analysis approaches—Cox model with pooled‐control data, Cox model with control arm‐specific frailty, and Bayesian analysis using a commensurate prior—were assessed. Overall survival was similar between the treatment arms. The direction and magnitude of hazard ratios (HRs) from the multiple HC analyses (HRs ranged from 1.02 to 1.06) were comparable with the reported trial HR (HR 0.91; 95% CI: 0.56, 1.49). This analysis demonstrates the feasibility and applicability of leveraging RWD in clinical trial design to supplement clinical trial control arms.

02 Dec 2024·Molecular Pharmaceutics

Pathophysiology-Driven Approaches for Overcoming Nanomedicine Resistance in Pancreatic Cancer

Review

Author: Nair, Sreejith Thrivikraman ; Unni, Ashok R. ; Mangalanandan, T S ; Pavithran, K. ; Sarma, Manjit ; Kamalasanan, Kaladhar ; Sithara, MS ; Abhi, C

Tumor heterogeneity poses a significant challenge in cancer therapy. To address this, we analyze pharmacotherapeutic challenges by categorizing them into static and dynamic barriers, reframing these challenges to improve drug delivery, efficacy, and the development of controlled-release nanomedicines (CRNMs). This pathophysiology-driven approach facilitates the design of novel therapeutics tailored to overcome obstacles in pancreatic ductal adenocarcinoma (PDAC) using nanotechnology. Advanced biomaterials in nanodrug delivery systems offer innovative solutions by combining controlled release, stimuli sensitivity, and smart design strategies. CRNMs are engineered to modulate spatiotemporal signaling and control drug release in PDAC, where resistance to conventional therapies is particularly high. This review explores pharmacokinetic considerations for nanomedicine design, RNA interference (RNAi) for stromal modulation, and the development of targeted nanomedicine strategies. Additionally, we highlight the limitations of current animal models in capturing the complexities of PDAC and discuss notable clinical failures, such as PEGylated hyaluronidase (Phase III HALO 109-301 trial) and evofosfamide (TH-302) with gemcitabine (MAESTRO trial), underscoring the need for improved models and treatment strategies. By targeting pathways like Notch and Hedgehog and incorporating stimuli-sensitive and pathway-modulating agents, CRNMs offer a promising avenue to enhance drug penetration and efficacy, reshaping the paradigm of pancreatic cancer treatment.

01 Sep 2024·Biomedicine & Pharmacotherapy

Hyaluronidase improves the efficacy of nab-paclitaxel after prolonged angiogenesis inhibition in preclinical models for esophagogastric cancer

Article

Author: Waasdorp, Cynthia ; Bijlsma, Maarten F ; Bootsma, Sanne ; Liu, Dajia ; Meijer, Sybren L ; Guo, Lihui ; van Laarhoven, Hanneke W M ; Oyarce, Cesar

BACKGROUNDLong-term anti-angiogenesis leads to pruned vasculature, densely deposited extracellular matrix (ECM), and consequently reduced chemotherapy delivery in esophagogastric cancer (EGC). To address this issue, we evaluated the efficacy of adding a hyaluronidase or a NO-donor to the regimen of chemotherapy and anti-angiogenic drugs.METHODSA patient-derived EGC xenograft model was developed. Grafted mice were randomly assigned to four experimental groups and one control group. The experimental groups received DC101, a murine angiogenesis inhibitor, and nab-paclitaxel (NPTX), with the addition of hyaluronidase (PEGPH20), or NO-donor (nitroglycerine, NTG), or their combination, respectively. We compared tumor growth during 17 days of treatment. We performed immunohistochemistry for ECM components hyaluronan (HA) and collagen, CD31 for endothelial cells, and γH2AX for DNA damage. The positively stained areas were quantified, and vessel diameters were measured using QuPath software.RESULTSProlonged DC101 treatment induced deposition of HA (p<0.01) and collagen (p<0.01). HA was effectively degraded by PEGPH20 (p<0.001), but not by NTG as expected. Both PEGPH20 (p<0.05) and NTG (p<0.01) dilated vessels collapsed in response to long-term DC101 treatment. However, only PEGPH20 (rather than NTG) was found to significantly inhibit tumor growth (p<0.05) in combination with NPTX and DC101.CONCLUSIONSThese findings suggest that the mechanical barrier of HA is the major reason responsible for the resistance developed during prolonged anti-angiogenesis in EGC. Incorporating PEGPH20 into the existing treatment regimen is promising to improve outcomes for patients with EGC.

10

News (Medical) associated with Pegvorhyaluronidase alfa

08 Sep 2023

·www.pmlive.com

ICR study finds way to determine efficacy of experimental breast cancer drugs

Researchers at The Institute of Cancer Research (ICR), London, have discovered a way to use a simple, non-invasive MRI scan to determine whether an experimental approach to enhance treatment for breast cancer is effective. New research from the study, funded by Cancer Research UK, could help doctors visualise tumours and speed up the development of targeted therapies for breast cancer. If successful, these drugs could enhance the effectiveness of other drugs administered in combination. Common features of breast cancer include excessive connective tissue, which consists of cells and fibres that provide a scaffold, known as the extracellular matrix (ECM), where tumours can grow. Hyaluronic acid, which works by absorbing water, is naturally present inside the tumour ECM and causes cancer tumours to swell, making it challenging for drugs to penetrate, reach and destroy cancer cells. Researchers are able to use experimental drugs that target and degrade a chemical called hyaluronic acid to dissolve some of the dense ECM and improve drug delivery to tumours. However, when using experimental drugs targeting the chemical in this way, it can be difficult for researchers to identify the exact time when the acid has been degraded, and therefore, it is a challenge to determine the best time to administer other drugs. The researchers performed multi-parametric MRI scans on mice with breast tumours to track the efforts of PEGPH20, an investigational drug targeting hyaluronic acid, to gain measurements that provide additional information about the tissue being analysed. Study leader, Simon Robinson, professor, magnetic resonance imaging of cancer, ICR, London, said: "Diffusion-weighted MRI can be performed on conventional clinical MRI scanners. Our new research shows that we can use such scans to check if [experimental] drugs like PEGPH20 are working, helping guide treatment in a more targeted and non-invasive way." For example, after using diffusion-weighted imaging to understand how water molecules moved within tissue, the researchers found that a measurement of water’s ability to move or spread, called the apparent diffusion coefficient (ADC), was reduced by up to 38% following administration of PEGPH20. The results suggest that PEGPH20 could make breast cancer tissue more accessible to chemotherapy drugs and could potentially improve treatment outcomes. Upon further necessary testing, the researchers hope to improve the development of targeted therapies for breast cancer and potentially other tumours.

13 Apr 2022

·www.biospace.com

Halozyme Picks Up Antares’ Drug Delivery Tech for Nearly $1B

Halozyme Therapeutics announced that it is acquiring Antares Pharma for $960 million in cash. The news caused Antares stock to rocket 47% in premarket trading. Halozyme Therapeutics announced Wednesday morning that it is acquiring Antares Pharma for $960 million in cash. The news caused Antares stock to rocket 47% in premarket trading. “The addition of Antares with its best-in-class auto injector platform and specialty commercial business, augments Halozyme’s strategy, further strengthens our position as a leading drug delivery company and extends our strategy to include specialty products,” said Dr. Helen Torley, president and chief executive officer of Halozyme. Torley added, “The acquisition of Antares fits well with our previously discussed strategic priorities and provides substantial financial growth potential and disruptive solutions to significantly improve patient experiences and outcomes for emerging and established therapies. Halozyme is well-positioned to leverage Antares’ value proposition, driven by a strong balance sheet, established industry relationships and business development experience.” On March 24, Halozyme inked a global collaboration and license deal with Roche subsidiary Chugai Pharmaceuticals, giving Chugai access to Halozyme’s ENHANZE drug delivery technology recombinant human hyaluronidase PH20 enzyme (rHuPH20). The target was not disclosed. Under the deal, Chugai paid Halozyme $25 million up front with potential milestones of up to $160 million. Halozyme will also be eligible for royalties on sales of any commercialized products using the ENHANZE technology. ENHANZE removes traditional limitations on the volume of biologics that can be injected subcutaneously, allowing biologics that could only be dosed intravenously to be delivered subcutaneously. Halozyme has deals with several companies for its ENHANZE technology, including Roche , Baxalta , Pfizer , AbbVie, Eli Lilly , Bristol-Myers Squibb, Alexion , argenx, Horizon Therapeutics, ViiV Healthcare and now Chugai. Antares is a specialty pharmaceutical company that develops and commercializes drugs and technologies for targeted therapeutic areas using its advanced drug delivery systems. Most recently, on March 29, it announced the U.S. Food and Drug Administration granted final approval for Tlando (testosterone undecanoate), an oral drug for testosterone replacement therapy indicated for disorders linked to a deficiency or absence of endogenous testosterone or hypogonadism in adult males. The company’s products include Xyosted, a weekly auto-injector testosterone therapy, Tlando, Nocdurna, a sublingual tablet for the treatment of nocturia due to nocturnal polyuria in adults who wake up at least twice a night to urinate, and Sumatriptan, a generic of Imitrex (sumatriptan succinate) to treat acute migraine with or without aura, and acute cluster headaches in adults. Halozyme has a market value of approximately $5.7 billion. In 2019, the company restructured after the failure of a metastatic pancreatic cancer drug in Phase III. In November 2019, Torley said the company would discontinue clinical development of the drug, PEGPH20, as well as its entire oncology operation. It intended to focus entirely on its ENHANZE technology. It also markets a range of custom drug delivery devices. Of the acquisition, Robert F. Apple, president and chief executive office of Antares, stated, “We are pleased to have reached this agreement with Halozyme, as this transaction showcases the value of Antares’ highly complementary business, provides our shareholders with attractive and certain value, and brings together industry-leading expertise and drug delivery platforms to accelerate growth and create new opportunities. As we remain committed to continuing to serve our partners, I would like to thank our employees for their hard work and dedication to this mission. We look forward to working with the Halozyme team to complete the transaction and deliver best-in-class therapies and drug delivery solutions.”

Drug ApprovalAcquisitionLicense out/inPhase 3

05 Nov 2019

·www.bioportfolio.com

Theramex Buys Janssen’s Evorel Amid Ongoing HRT Shortages

Amid ongoing manufacturing issues with its own HRT patches, women’s health spin-out Theramex acquires global rights to Janssen’s Evorel patches... Related Stories Turkey’s Domestic Vaccine Production Drive Prompts New Partnerships Takeda Sheds Products, Employees To Stada In $660m Move Halozyme’s Spotlight Shifts To Enhanze Exclusively After PEGPH20 Fails In Phase III

Vaccine

100 Deals associated with Pegvorhyaluronidase alfa

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External Link

KEGG	Wiki	ATC	Drug Bank
D11201	-	-	DB14912

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Pancreatic Ductal Adenocarcinoma	Phase 2	Denmark	Halozyme Therapeutics, Inc.	14 Mar 2016
Pancreatic Ductal Adenocarcinoma	Phase 2	Germany	Halozyme Therapeutics, Inc.	14 Mar 2016
Pancreatic Ductal Adenocarcinoma	Phase 2	United Kingdom	Halozyme Therapeutics, Inc.	14 Mar 2016
Pancreatic Ductal Adenocarcinoma	Phase 2	Spain	Halozyme Therapeutics, Inc.	14 Mar 2016
Pancreatic Ductal Adenocarcinoma	Phase 2	Croatia	Halozyme Therapeutics, Inc.	14 Mar 2016
Pancreatic Ductal Adenocarcinoma	Preclinical	Croatia	Halozyme Therapeutics, Inc.	14 Mar 2016
Pancreatic Ductal Adenocarcinoma	Preclinical	Denmark	Halozyme Therapeutics, Inc.	14 Mar 2016
Pancreatic Ductal Adenocarcinoma	Preclinical	Spain	Halozyme Therapeutics, Inc.	14 Mar 2016
Pancreatic Ductal Adenocarcinoma	Preclinical	United Kingdom	Halozyme Therapeutics, Inc.	14 Mar 2016
Pancreatic Ductal Adenocarcinoma	Preclinical	Germany	Halozyme Therapeutics, Inc.	14 Mar 2016

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EASD2022	Not Applicable	Glomerular disease HA \| CD44 +	-	PEGPH20	oanjiavixa(sdoixqfppn) = mkawzxhwvd nbgngdvuvn (otyoiulbfg ) View more	Positive	22 Sep 2022
				Vehicle	oanjiavixa(sdoixqfppn) = fwaijbecvv nbgngdvuvn (otyoiulbfg ) View more
NCT01839487 (HALO109-202, Pubmed \| J Transl Med)	Phase 2	Metastatic Pancreatic Ductal Adenocarcinoma	279	Pegvorhyaluronidase alfa plus nab-paclitaxel/gemcitabine	(aecqcmfvtp) = jkmnyakscm szqowuoelz (ohdtjfyjnq ) View more	Positive	21 Jan 2021
				Nab-paclitaxel/gemcitabine	(aecqcmfvtp) = jyusqnjhgg szqowuoelz (ohdtjfyjnq ) View more
NCT03979066 (NEOiPANC, CTgov)	Phase 2	Pancreatic Ductal Adenocarcinoma	1	atezolizumab (Atezolizumab)	glcpprtuvk(rxwjygcpse) = fqpwavahfv qhvjihfcky (klryayicuv, hzopcopvod - uidsvmhzib) View more	-	23 Dec 2020
				atezolizumab+PEGPH20 (Atezolizumab in Combination With PEGPH20)	glcpprtuvk(rxwjygcpse) = mrbqmjltwn qhvjihfcky (klryayicuv, zbwpgjugqt - gefnuiqqbu) View more
NCT02715804 (HALO 109-301, Pubmed \| J Urol) Manual	Phase 3	Pancreatic adenocarcinoma metastatic First line	492	Nab-Paclitaxel+Gemcitabine+Pegvorhyaluronidase Alfa	(neehkkueyg) = gieplakxgc anelmcbunk (wlvfmbipbo ) View more	Negative	20 Sep 2020
				Nab-Paclitaxel+Gemcitabine+Placebo	(neehkkueyg) = fvhtfufvev anelmcbunk (wlvfmbipbo ) View more
NCT02715804 (HALO 109-301, CTgov)	Phase 3	Pancreatic Ductal Adenocarcinoma	492	nab-Paclitaxel+Gemcitabine+PEGPH20 (PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine)	(zkpyqkrsgx) = miziyrxcit jtyxuahhze (pvmqzbkebk, tafgjzglpt - rvruudpfkj) View more	-	14 Jul 2020
				Placebo+nab-Paclitaxel+Gemcitabine (AG: Placebo + Nab-Paclitaxel + Gemcitabine)	(zkpyqkrsgx) = qndfenaafv jtyxuahhze (pvmqzbkebk, lapbccbqsm - wxpgisslnn) View more
NCT03193190 \| NCT03281369 (ASCO 12020 \| ASCO 22020) Manual	Phase 1/2	Pancreatic Ductal Adenocarcinoma \| Stomach Cancer Second line	133	atezolizumab+PEGPH20 (M-PDAC)	(yriylslukq) = niwidpqskf zxdzpzvbyy (jwdlafiayb ) View more	Negative	25 May 2020
				mFOLFOX6 or gemcitabine + nab-paclitaxel (M-PDAC)	(yriylslukq) = zrnhckcork zxdzpzvbyy (jwdlafiayb ) View more
NCT01959139 (SWOG S1313 \| S1313, CTgov)	Phase 1/2	Pancreatic adenocarcinoma metastatic \| Metastatic Pancreatic Cancer	126	Leucovorin+Irinotecan+Oxaliplatin+5-fluorouracil (Phase II: mFOLFIRINOX)	jcffeuahix(hbsttfvnyc) = dibxhjojsx shxouaijon (climtwauda, vieaygskov - glzsxsfngs) View more	-	12 Feb 2020
				Leucovorin+Irinotecan+Oxaliplatin+PEGPH20+5-fluorouracil (Phase II: mFOLFIRINOX + PEGPH20)	jcffeuahix(hbsttfvnyc) = genebpiprq shxouaijon (climtwauda, htuqyeyvbf - njwrdntikx) View more
NCT03267940 (CTgov)	Phase 1	Intrahepatic Cholangiocarcinoma \| Unresectable Intrahepatic Cholangiocarcinoma \| Gallbladder adenocarcinoma	85	GEM+CIS+PEGPH20 (Run-in Portion: PEGCISGEM)	rlxquxhyws(oxuemnommw) = gzuywtgrko zstymbrngg (cpijvnmhmo, xwolwbfpnx - awhiskmkup) View more	-	07 Feb 2020
				GEM+atezolizumab+CIS+PEGPH20 (Run-in Portion: PEGCISGEMATEZO)	rlxquxhyws(oxuemnommw) = ulvcsbhvdy zstymbrngg (cpijvnmhmo, wnevzhitux - zkbcektheo) View more
NCT02715804 (HALO 109-301, ASCO_GI2020)	Phase 3	Metastatic Pancreatic Ductal Adenocarcinoma	494	PEGPH20 + nab-paclitaxel/gemcitabine	ofuqitlqef(evqpgmcnkb) = neutropenia (44% vs 47%), thrombocytopenia (21% vs 16%) and fatigue (16% vs 10%); G3+ rates were 6% vs 7% for TE events, 5% vs 2% for bleeding events and 13% vs 5% for musculoskeletal events. ewvwaqespo (kigbeiiuoo ) View more	Negative	04 Feb 2020
				Placebo + nab-paclitaxel/gemcitabine

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