A Phase 1, Open-label Study in Healthy Participants to Investigate the Effect of Multiple-dose JNJ-56136379 on the Single-dose Pharmacokinetics of Bictegravir, Emtricitabine, and Tenofovir Alafenamide

The purpose of this study is to evaluate the effect of multiple-dose JNJ-56136379 on the single-dose pharmacokinetics (PK) of the combination of bictegravir (BIC), emtricitabine (FTC), tenofovir alafenamide (TAF) in healthy adult participants.

Start Date06 May 2021

Sponsor / Collaborator

Janssen Research & Development LLC

NCT04585789 / CompletedPhase 2

A Phase 2 Randomized, Open-label, Parallel-group, Multicenter Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Response to Combination Regimens Containing JNJ-73763989 and Nucleos(t)Ide Analog With or Without JNJ-56136379 in Patients With Chronic Hepatitis B Virus Infection

The purpose of this study is to assess changes in intrahepatic hepatitis B surface antigen (HBsAg) between baseline and on-treatment liver biopsy in response to JNJ-3989-based combination treatment.

Start Date11 Mar 2021

Sponsor / Collaborator

Janssen Research & Development LLC

EUCTR2019-004475-39-BE / Not yet recruitingPhase 2

A Phase 2 Randomized, Open-label, Parallel-group, Multicenter Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Response to Combination Regimens Containing JNJ-73763989 and Nucleos(t)ide Analog With or Without JNJ-56136379 in Patients With Chronic Hepatitis B Virus Infection. - INSIGHT

Start Date21 Sep 2020

Sponsor / Collaborator

Janssen Sciences Ireland Unlimited Co.

100 Clinical Results associated with Bersacapavir

100 Translational Medicine associated with Bersacapavir

100 Patents (Medical) associated with Bersacapavir

Literatures (Medical) associated with Bersacapavir

RSC advances

Binding characteristics of pyrrole-scaffold hepatitis B virus capsid inhibitors and identification of novel potent compounds

Article

Author: Meeprasert, Arthitaya ; Chuaypen, Natthaya ; Dunkoksung, Wilasinee ; Deesiri, Sirikan ; Ruengsatra, Tanachote ; Pudhom, Khanitha ; Srisa, Jakkrit ; Prueksaritanont, Thomayant ; Vimolmangkang, Sornkanok ; Udomnilobol, Udomsak ; Kiatbumrung, Rattanaporn ; Tangkijvanich, Pisit ; Rattanangkool, Eakkaphon

Using computational approaches to analyze the binding characteristics of pyrrole-scaffold inhibitors, leading to the discovery of a novel structural series and the identification of a promising lead compound.

01 Sep 2023·The lancet. Gastroenterology & hepatology

Efficacy and safety of the siRNA JNJ-73763989 and the capsid assembly modulator JNJ-56136379 (bersacapavir) with nucleos(t)ide analogues for the treatment of chronic hepatitis B virus infection (REEF-1): a multicentre, double-blind, active-controlled, randomised, phase 2b trial

Article

BACKGROUND:

JNJ-73763989 (JNJ-3989), a small interfering RNA, targets all hepatitis B virus (HBV) RNAs, reducing all HBV proteins. JNJ-56136379 (JNJ-6379; also known as bersacapavir), a capsid assembly modulator, inhibits HBV replication. We aimed to evaluate the efficacy (ie, antiviral activity) and safety of these therapeutics in combination with nucleos(t)ide analogues in patients with chronic hepatitis B.

METHODS:

The REEF-1 multicentre, double-blind, active-controlled, randomised, phase 2b study was done at 108 hospitals or outpatient centres across 19 countries in Asia, Europe, and North and South America. We included patients aged 18-65 years with chronic hepatitis B (defined as HBsAg positivity at screening and at least 6 months before screening or alternative markers of chronicity [eg, HBV DNA]), including those not currently treated, virologically suppressed, HBeAg positive, and HBeAg negative. Patients were randomly assigned (1:1:2:2:2:2) via permuted block randomisation according to a computer-generated schedule to receive oral nucleos(t)ide analogues once per day plus placebo (control group); oral JNJ-6379 250 mg daily plus nucleos(t)ide analogues (JNJ-6379 dual group); nucleos(t)ide analogues plus subcutaneously injected JNJ-3989 at doses of 40 mg (JNJ-3989 dual 40 mg group), 100 mg (JNJ-3989 dual 100 mg group), or 200 mg (JNJ-3989 dual 200 mg group) every 4 weeks; or JNJ-6379 250 mg plus JNJ-3989 100 mg every 4 weeks plus nucleos(t)ide analogues (triple group) for 48 weeks followed by a follow-up phase. An interactive web response system provided concealed treatment allocation, and investigators remained masked to the intervention groups until the primary analysis at week 48. The primary endpoint was the proportion of patients meeting predefined nucleos(t)ide analogue-stopping criteria (alanine aminotransferase <3 × upper limit of normal, HBV DNA below the lower limit of quantitation, HBeAg negative, and HBsAg <10 IU/mL) at week 48. All patients who received at least one dose of study drug were included in the analysis population used for primary efficacy assessment, excluding those who withdrew because of COVID-19-related reasons, withdrew before week 44, or had no efficacy data (ie, the modified intention-to-treat population). Safety was assessed in all participants who received at least one dose of study drugs. This trial is registered with ClinicalTrials.gov, NCT03982186. The study has been completed.

FINDINGS:

Between Aug 1, 2019, and April 26, 2022, 470 patients (310 [66%] male and 244 [52%] White) were randomly assigned: 45 to the control group, 48 to the JNJ-6379 dual group, 93 to the JNJ-3989 dual 40 mg group, 93 to the JNJ-3989 dual 100 mg group, 96 to the JNJ-3989 dual 200 mg group, and 95 to the triple group. At week 48, five (5%; 90% CI 2-11) of 91 patients in the JNJ-3989 dual 40 mg group, 15 (16%; 10-24) of 92 in the JNJ-3989 dual 100 mg group, 18 (19%; 13-27) of 94 in the JNJ-3989 dual 200 mg group, eight (9%; 4-15) of 94 in the triple group, and one (2%; 0-10) of 45 in the control group met nucleos(t)ide analogue stopping criteria. No patients in the JNJ-6379 dual group met stopping criteria. 38 (81%) patients who met nucleos(t)ide analogue-stopping criteria at week 48 were virologically suppressed and HBeAg negative at baseline. Ten (2%) of 470 patients had serious adverse events during the treatment phase, and two patients (one each from the JNJ-3989 dual 200 mg group [exercise-related rhabdomyolysis] and the triple group [increase in ALT or AST]) had serious adverse events related to study treatment. During follow-up, 12 (3%) of 460 patients had a serious adverse event; one (<1%), a gastric ulcer, was considered to be related to nucleos(t)ide analogues and occurred in a patient from the JNJ-3989 dual 200 mg group. 29 (6%) of 460 patients in the treatment phase and in ten (2%) of 460 patients in the follow-up phase had grade 3 or 4 adverse events. Five (1%) of 470 patients discontinued treatment due to adverse events, and there were no deaths.

INTERPRETATION:

Although treatment with JNJ-3989 led to a dose-dependent response for meeting nucleos(t)ide analogue-stopping criteria, it rarely led to HBsAg seroclearance. However, most patients treated with JNJ-3989 had clinically meaningful reductions in HBsAg that might contribute to a liver environment conducive to better immune control and, in turn, might improve the response to immune-modulating therapies.

FUNDING:

Janssen Research and Development.

01 Jul 2023·Gut

Randomised phase 2 study (JADE) of the HBV capsid assembly modulator JNJ-56136379 with or without a nucleos(t)ide analogue in patients with chronic hepatitis B infection

Article

Author: Talloen, Willem ; Beumont, Maria ; Bourgeois, Stefan ; Buti, Maria ; Chan, Henry L Y ; Asselah, Tarik ; Zoulim, Fabien ; Biermer, Michael ; Lampertico, Pietro ; Kalmeijer, Ronald ; Janssen, Harry L A ; Nahass, Ronald G ; Lenz, Oliver ; Vandenbossche, Joris ; Verbinnen, Thierry ; Janczewska, Ewa ; Shukla, Umesh ; Tanaka, Yasuhito ; Hou, Jinlin

Objective:

We present the final analysis results of the phase 2 JADE study (ClinicalTrials.gov Identifier:NCT03361956).

Design:

232 patients with chronic hepatitis B (CHB) not currently treated at study start (NCT) at study start or virologically suppressed were randomised to receive 75 mg (part 1) or 250 mg (part 2) JNJ-56136379, a hepatitis B virus (HBV)–capsid assembly modulator, one time per day or placebo with nucleos(t)ide analogue (NA) (tenofovir disoproxil fumarate/entecavir) or JNJ-56136379 alone (NCT-only) for ≥24 and ≤48 weeks.

Results:

In patients who are NCT hepatitis B e-antigen (HBeAg) positive, JNJ-56136379 75 mg+NA and 250 mg+NA showed limited mean (SE) hepatitis B surface antigen (HBsAg) declines (0.14 (0.10) and 0.41 (0.15), respectively) from baseline at Week 24 (primary endpoint; placebo+NA: 0.25 (0.11) log10international unit (IU)/mL).In patients who are NCT HBeAg positive, mean (SE) HBV DNA declines at Week 24 were 5.53 (0.23) and 5.88 (0.34) for JNJ-56136379 75 mg+NA and 250 mg+NA, respectively, versus 5.21 (0.42) log10IU/mL for placebo+NA. In NCT patients, mean (SE) HBV RNA declines were 2.96 (0.23) and 3.15 (0.33) versus 1.33 (0.32) log10copies/mL, respectively.Patients with HBsAg declines had HBeAg and hepatitis B core-related antigen (HBcrAg) declines and some early on-treatment isolated alanine aminotransferase flares. Viral breakthrough occurred with JNJ-56136379 monotherapy with the emerging resistant-variant T33N, but not with JNJ-56136379+NA. JNJ-56136379 treatment beyond Week 24 had a generally small additional effect on viral markers.No study treatment-related serious adverse events or clinically significant changes in laboratory parameters occurred.

Conclusions:

In patients with non-cirrhotic CHB, JNJ-56136379+NA showed pronounced reductions in HBV DNA and HBV RNA, limited HBsAg or HBeAg declines in patients who are NCT HBeAg positive, and was well tolerated, but no clear benefit with regards to efficacy of JNJ-56136379 over NA was observed.

News (Medical) associated with Bersacapavir

07 Jun 2022

·www.biospace.com

Arrowhead Pharmaceuticals to Participate in Upcoming June 2022 Conferences

June 7, 2022 11:30 UTC PASADENA, Calif.--(BUSINESS WIRE)-- Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced that it is scheduled to participate in the following upcoming events: Jefferies Healthcare Conference – June 8-10, 2022 Type: Fireside chat presentation Presenter: Vincent Anzalone, Vice President Finance and Investor Relations, Arrowhead Pharmaceuticals Goldman Sachs 43rd Annual Global Healthcare Conference – June 13-16, 2022 Type: Fireside chat presentation Presenter: Vincent Anzalone, Vice President Finance and Investor Relations, Arrowhead Pharmaceuticals The International Liver Congress™ 2022 - The Annual Meeting of the European Association for the Study of the Liver (EASL) – June 22-26, 2022 Title: Effects of the siRNA JNJ-3989 and/or the Capsid Assembly Modulator JNJ-6379 on Viral Markers of Chronic Hepatitis B: Results From the REEF-1 Study Presenter: Man-Fung Yuen, Department of Medicine & State Key Laboratory of Liver Research, Queen Mary Hospital, The University of Hong Kong Title: Understanding the Dynamics of HBsAg Decline Through Model-informed Drug Development (MIDD) of siRNA and CAM-N for the Treatment of Chronic Hepatitis B (CHB) Virus Infection Presenter: Huybrecht T’jollyn, Janssen Research & Development Title: Efficacy and Safety of Finite 48-week Treatment With the siRNA JNJ-3989 and the Capsid Assembly Modulator JNJ-6379 in HBeAg Negative Virologically Suppressed Chronic Hepatitis B Patients: Results from the REEF-2 Study Presenter: Kosh Agarwal, Institute of Liver Studies, King’s College Hospital Title: Reduction of Intra-hepatic Z-AAT Synthesis by Fazirsiran Decreases Globule Burden and Improves Histological Measures of Liver Disease in Adults with Alpha-1 Antitrypsin Deficiency Presenter: Pavel Strnad, Department of Internal Medicine III, University Hospital, Rwth Aachen A copy of the presentation materials and webcast links may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website. About Arrowhead Pharmaceuticals Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing. For more information, please visit , or follow us on Twitter @ArrowheadPharma. To be added to the Company's email list and receive news directly, please visit . Safe Harbor Statement under the Private Securities Litigation Reform Act: This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Any statements contained in this release except for historical information may be deemed to be forward-looking statements. Without limiting the generality of the foregoing, words such as “may,” “will,” “expect,” “believe,” “anticipate,” “hope,” “intend,” “plan,” “project,” “could,” “estimate,” or “continue” are intended to identify such forward-looking statements. In addition, any statements that refer to projections of our future financial performance, trends in our business, expectations for our product pipeline or product candidates, including anticipated regulatory submissions and clinical program results, prospects or benefits of our collaborations with other companies, or other characterizations of future events or circumstances are forward-looking statements. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of numerous factors and uncertainties, including the impact of the ongoing COVID-19 pandemic on our business, the safety and efficacy of our product candidates, decisions of regulatory authorities and the timing thereof, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the likelihood and timing of the receipt of future milestone and licensing fees, the future success of our scientific studies, our ability to successfully develop and commercialize drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, the enforcement of our intellectual property rights, and the other risks and uncertainties described in our most recent Annual Report on Form 10-K, subsequent Quarterly Reports on Form 10-Q and other documents filed with the Securities and Exchange Commission from time to time. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances. Source: Arrowhead Pharmaceuticals, Inc.

CollaboratesiRNA

09 Apr 2021

·www.globenewswire.com

Hepatitis B Virus Infection - Global Drug Forecast and Market Analysis to 2029

New York, April 09, 2021 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Hepatitis B Virus Infection - Global Drug Forecast and Market Analysis to 2029" - For most patients, CHB is a lifelong disease that cannot be cured, with only a very small number of patients entering remission each year.Patients with CHB have a 20% risk of developing life-threatening liver disease, such as cirrhosis and hepatocellular carcinoma (HCC) as a result of their condition.Guidelines by the American Association of the Study of Liver Diseases (AASLD) and the European Association for the Study of Liver (EASL) have recommended CHB to be treated with nucleotide analogs (NA).Gilead Sciences and Bristol Myers Squibb (BMS) are the major players within the CHB market with their nucleotide analogs Viread (TDF, Gilead), Vemlidy (TAF, Gilead) and Baraclude (entecavir, BMS).However, generic versions of TDF and entecavir dominate the 9MM.The CHB treatment pipeline is predominantly in early stages.Gilead’s TLR-8 agonist selgantolimod, J&J’s capsid assembly modulator JNJ-6379, and antisense nucleotide JNJ-3898 could significantly impact the CHB market across the 9MM.Also Replicor, Assembly Biosciences, and Ionis Pharmaceuticals are developing CHB therapies. A major unmet for CHB treatment remains the potential to achieve functional cure.Key Highlights- During the 10-year forecast period, there are six major pipeline products that are on track to launch, driving a forecast growth in the 9MM from $3.8B in 2019 to $5.2B in 2029, which represents a CAGR of 3.1%.- To combat the unmet need of a functional cure, companies such as Gilead, J&J, Replicor, Ionis, and Assembly Biosciences are developing pipeline products with novel mechanism of action, with the potential of being used as a combination therapy either with current nucleotide analogs or with emerging products.- The pipeline products are expected to launch in the second half of the forecast period in 2029. Antisense nucleotides are expected to gain a market share of 14.7% and sales of $761M in the 9MM by 2029. However, capsid assembly modulators from J&J and a toll-like receptor 8 agonist from Gilead are expected to compete with antisense nucleotides for market shares in the 9MM by the end of the forecast period.Key Questions Answered- How will the CHB market landscape in the 9MM (US, France, Germany, Italy, Spain, UK, Japan, Brazil, China) change from 2019-2029?- What are the most promising late-stage pipeline products for CHB treatment?- How do the clinical and commercial attributes of late-stage pipeline products compare with one another, and against existing CHB treatment options?- What are the remaining unmet needs in CHB treatment?- What drivers and barriers will affect CHB treatment sales in the 9MM over the forecast period?Scope- Overview of CHB, including epidemiology, etiology, pathophysiology, symptoms, diagnosis, and current management strategies.- Topline CHB treatment market revenue from 2019-2029. Annual cost of therapy and major pipeline product sales in this forecast period are included.- Key topics covered include current CHB treatment, unmet needs and opportunities, and the drivers and barriers affecting CHB treatment sales in the 9MM.- Pipeline analysis: comprehensive data split across different phases, emerging novel trends under development, synopses of innovative early-stage projects, and detailed analysis of late-stage pipeline products.- Analysis of the current and future market competition in the global CHB treatment market. Insightful review of the key industry drivers, constraints, and challenges. Each trend is independently researched to provide qualitative analysis of its implications.Reasons to BuyThe report will enable you to -- Develop and design your in-licensing and out-licensing strategies through a review of pipeline products and technologies, and by identifying the companies with the most robust pipeline.- Develop business strategies by understanding the trends shaping and driving the global Hepatitis B Virus Infection market.- Drive revenues by understanding the key trends, innovative products and technologies, market segments, and companies likely to impact the Hepatitis B Virus Infection market in the future.- Formulate effective sales and marketing strategies by understanding the competitive landscape and by analyzing the performance of various competitors.- Identify emerging players with potentially strong product portfolios and create effective counter-strategies to gain a competitive advantage.- Organize your sales and marketing efforts by identifying the market categories and segments that present maximum opportunities for consolidations, investments, and strategic partnerships.Read the full report: ReportlinkerReportLinker is an award-winning market research solution. Reportlinker finds and organizes the latest industry data so you get all the market research you need - instantly, in one place.__________________________

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis B, Chronic	Phase 2	US	Janssen Sciences Ireland Uc	13 Feb 2018
Hepatitis B, Chronic	Phase 2	US	Janssen Research & Development LLC	13 Feb 2018
Hepatitis B, Chronic	Phase 2	CN	Janssen Sciences Ireland Uc	13 Feb 2018
Hepatitis B, Chronic	Phase 2	JP	Janssen Sciences Ireland Uc	13 Feb 2018
Hepatitis B, Chronic	Phase 2	JP	Janssen Research & Development LLC	13 Feb 2018
Hepatitis B, Chronic	Phase 2	BE	Janssen Sciences Ireland Uc	13 Feb 2018
Hepatitis B, Chronic	Phase 2	BE	Janssen Research & Development LLC	13 Feb 2018
Hepatitis B, Chronic	Phase 2	BE	Xian Janssen Pharmaceutical Ltd.	13 Feb 2018
Hepatitis B, Chronic	Phase 2	CA	Janssen Research & Development LLC	13 Feb 2018
Hepatitis B, Chronic	Phase 2	CA	Janssen Sciences Ireland Uc	13 Feb 2018

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03982186 (REEF-1, Pubmed) Manual	Phase 2	Hepatitis B, Chronic First line	470	JNJ-6379+JNJ-3989 (JNJ-3989 dual 40 mg group)	tlqxrknnhj(vbdcxplpeh) = pppcyhsfag azojauiytp (wvcikryisx, 2 - 11)	Positive	10 Jul 2023
				JNJ-6379+JNJ-3989 (JNJ-3989 dual 100 mg group)	tlqxrknnhj(vbdcxplpeh) = sbqfdbyviv azojauiytp (wvcikryisx, 10 - 24)
NCT03361956 (JADE, Pubmed)	Phase 2	Hepatitis B, Chronic	232	JNJ-56136379 75 mg+NA	jionnzaovt(oqqtdtebzy) = rqyqfwzvuk mhrerwrxfc (ixrmbjuput ) View more	Positive	25 Jan 2023
				JNJ-56136379 250 mg+NA	jionnzaovt(oqqtdtebzy) = yzxquidyij mhrerwrxfc (ixrmbjuput ) View more
NCT04129554 (REEF-2, Corporate Publications) Manual	Phase 2	Hepatitis B, Chronic HBeAg Negative	130	ETV/TDF/TAF+JNJ 73763989+JNJ 56136379	ywzwysvzfe(fvltpkmkta) = rxufzlhxjz tsrpvsdwni (yqhzevauwa ) View more	Negative	27 Jun 2022
				ETV/TDF/TAF+Placebo+Placebo	ywzwysvzfe(fvltpkmkta) = zrfyvosxas tsrpvsdwni (yqhzevauwa ) View more
NCT03982186 (REEF-1, EASL2022)	Phase 2	Hepatitis B, Chronic HBeAg+ \| HBeAg-	470	JNJ-3989 100 mg	nfyjopnhof(hlxsmnzflz) = tyzkqpdwfx xzgqhuywmp (gymvgcucvm )	-	25 Jun 2022
				JNJ-3989 200 mg	nfyjopnhof(hlxsmnzflz) = wpvtxigvoq xzgqhuywmp (gymvgcucvm ) View more
EASL2022	Phase 2	Hepatitis B, Chronic Add-on	130	JNJ-3989 200 mg SC Q4W	uoqjrlpsls(miixupanls) = eprvakujsx vefemimtrc (kpuaxfzvct ) View more	Positive	24 Jun 2022
				Placebo	uoqjrlpsls(miixupanls) = tvhswhslvo vefemimtrc (kpuaxfzvct ) View more
NCT02662712 (EASL2019)	Phase 1	Hepatitis B, Chronic HBcrAg \| HBeAg-positive \| HBsAg	57	JNJ-6379 25 mg	qwqfyawmrh(wwnlpvymum) = dfekdetlrn pqoizzlrbv (yimtnuodny, 1.3)	-	12 Apr 2019
				JNJ-6379 75 mg	qwqfyawmrh(wwnlpvymum) = fdnjxmobil pqoizzlrbv (yimtnuodny, 1.5)
NCT02662712 (EASL2019)	Phase 2	Hepatitis B, Chronic	57	JNJ-6379 75 mg	xbskepqxzp(rllhgglawy) = oaalqvlpuc aykmuhggjb (oecvwtawhj )	-	12 Apr 2019

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