A Phase 3 Study to Evaluate the Safety and Pharmacokinetics of Berotralstat Prophylaxis in Children With Hereditary Angioedema Who Are 2 to < 12 Years of Age

The purpose of this study is to evaluate the pharmacokinetics (PK) and safety of berotralstat to determine the appropriate weight-based dose for pediatric participants 2 to < 12 years old for prophylactic treatment to prevent attacks of hereditary angioedema (HAE).

Start Date25 Oct 2022

Sponsor / Collaborator

BioCryst Pharmaceuticals, Inc.

NCT04933721 / Active, not recruitingPhase 3

An Open-label Study to Provide Berotralstat Access to Subjects With Type 1 and 2 Hereditary Angioedema Who Were Previously Enrolled in Berotralstat Studies

This is a phase 3b open-label study providing access to berotralstat for HAE patients who were previously enrolled in berotralstat studies.

Start Date23 Jul 2021

Sponsor / Collaborator

BioCryst Pharmaceuticals, Inc.

NCT03873116 / CompletedPhase 3

A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Two Dose Levels of BCX7353 as an Oral Treatment for the Prevention of Attacks in Subjects With Hereditary Angioedema

This is a phase 3, multi-center, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of oral BCX7353 in preventing acute angioedema attacks in patients with Type I and Type II HAE who live in Japan.

Start Date27 Dec 2018

Sponsor / Collaborator

BioCryst Pharmaceuticals, Inc.

100 Clinical Results associated with Berotralstat Hydrochloride

100 Translational Medicine associated with Berotralstat Hydrochloride

100 Patents (Medical) associated with Berotralstat Hydrochloride

Literatures (Medical) associated with Berotralstat Hydrochloride

01 Dec 2024·PEDIATRIC ALLERGY AND IMMUNOLOGY

Hereditary angioedema in children: Review and practical perspective for clinical management

Review

Author: Blanc, Sibylle ; Boccon‐Gibod, Isabelle ; Bouillet, Laurence ; Villedieu, Mona ; Carbasse, Aurélia ; Nugues, Frédérique ; Bourgoin‐Heck, Mélisande ; Audouin‐Pajot, Christine ; Hoarau, Cyrille ; Dermesropian, Angelina ; Pagnier, Anne ; Voidey, Mélanie ; Jurquet, Anne‐Laure ; Kevorkian‐Verguet, Charlotte ; Reumaux, Héloïse

Abstract:

Background:

Hereditary angioedema (HAE) in children has specific features and requires multidisciplinary management.

Methods:

We performed a literature search and underwent in‐depth discussions to provide practical tools for physicians.

Results:

HAE is a rare, life‐threatening genetic disorder. Its epidemiology is poorly documented in children. Clinical manifestations usually appear during childhood or early adolescence. Classical signs, often preceded by prodromal symptoms, include transient, localized, non‐pitting, non‐pruritic swelling of deep dermal/subcutaneous or mucosal/submucosal tissues, leading to oedema of the extremities, face, lips, tongue, trunk and genitals, recurring gastrointestinal symptoms and laryngeal edema possibly causing asphyxiation and death. Diagnosis is often delayed due to low awareness in the medical community, and particularly challenging in case of isolated abdominal crises or atypical presentation and in neonates or infants. It relies on biological tests (measurement of serum/plasma levels of C1INH function, C1INH protein, and C4), genetic testing in selected cases, and imaging for differential diagnosis of acute abdominal crises. Main differential diagnosis for peripheral oedema is mast cell‐mediated oedema that accounts for 95% of angioedema in clinical practice. Quality of life can be significantly impaired. Disease management includes treatment of attacks, short‐term and long‐term prophylaxis, psychological support, avoidance of triggers, patients’ and parents’ education and coordination of all stakeholders, ideally within a specialized healthcare network. New plasma kallikrein inhibitors, namely lanadelumab (subcutaneous route) and berotralstat (oral route) have facilitated long‐term prophylaxis thanks to improved usability.

Conclusion:

Diagnostic and treatment of HAE are particularly challenging in children and require specific management by multiple stakeholders.

01 Sep 2024·Clinical and Translational Allergy

Advent of oral medications for the treatment of hereditary angioedema

Review

Author: Caballero, Teresa ; Frade, Joao P. ; Audhya, Paul K. ; Valerieva, Anna ; Magerl, Markus ; Craig, Timothy

Abstract:

Background:

Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable, debilitating episodes of submucosal and/or subcutaneous tissue swelling, which may be life‐threatening depending on anatomic location. The two primary management strategies for HAE are ready access to effective on‐demand treatment in all patients and the prevention of attacks (short‐term prophylaxis [STP] and long‐term prophylaxis [LTP]) in appropriate patients. All approved on‐demand and most LTP medications require subcutaneous or intravenous administration. Injection‐related challenges include trypanophobia (fear of needles), difficulty with self‐administration, injection‐site reactions (e.g., pain, erythema, bleeding, bruising), and anxiety—all contributing to poor compliance and administration delays. Oral HAE treatments may improve outcomes by reducing treatment barriers.

Aim:

To review oral therapies, approved or in development, for on‐demand treatment and/or prevention of HAE attacks.

Materials and Methods:

To provide a comprehensive review, data was obtained from publicly available resources through a targeted PubMed literature review and supplemented by information provided on company websites (search cutoff of May 31, 2024).

Results:

Berotralstat, an oral plasma kallikrein (PKa) inhibitor, is approved for LTP. Sebetralstat, another PKa inhibitor, is the investigational first oral on‐demand HAE treatment to complete a phase 3 trial. Deucrictibant, an oral bradykinin B2 receptor antagonist, has completed phase 2 trials for on‐demand therapy and LTP. Several other oral PKa inhibitors (ATN249, VE‐4666, and VE‐4062) are in early development for LTP.

Conclusion:

Substantial advances have been made in the development of oral treatments for HAE. These treatments have the potential to improve and optimize clinical outcomes, satisfaction, and quality of life among patients with HAE.

01 Jun 2024·CELL BIOCHEMISTRY AND BIOPHYSICS

Unveiling therapeutic frontiers: DON/DRP-104 as innovative Plasma kallikrein inhibitors against carcinoma-associated hereditary angioedema shocks - a comprehensive molecular dynamics exploration

Article

Author: Oduro-Kwateng, Ernest ; Soliman, Mahmoud E S

Abstract:

Human plasma kallikrein (PKa) is a member of the serine protease family and serves as a key mediator of the kallikrein-kinin system (KKS), which is known for its regulatory roles in inflammation, vasodilation, blood pressure, and coagulation. Genetic dysregulation of KKS leads to Hereditary Angioedema (HAE), which is characterized by spontaneous, painful swelling in various body regions. Importantly, HAE frequently coexists with various cancers. Despite substantial efforts towards the development of PKa inhibitors for HAE, there remains a need for bifunctional agents addressing both anti-cancer and anti-HAE aspects, especially against carcinoma-associated comorbid HAE conditions. Consequently, we investigated the therapeutic potential of the anti-glutamine prodrug, isopropyl(S)-2-((S)-2-acetamido-3-(1H-indol-3-yl)-propanamido)-6-diazo-5-oxo-hexanoate (DRP-104), and its active form, 6-Diazo-5-oxo-l-norleucine (DON), recognized for their anti-cancer properties, as novel PKa inhibitors. Utilizing structure-based in silico methods, we conducted a comparative analysis with berotralstat, a clinically approved HAE prophylactic, and sebetralstat, an investigational HAE therapeutic agent, in Phase 3 clinical trials. Inhibiting PKa with DON resulted in relatively heightened structural stability, rigidity, restricted protein folding, and solvent-accessible loop exposure, contributing to increased intra-atomic hydrogen bond formation. Conversely, PKa inhibition with DRP-104 induced restricted residue flexibility and significantly disrupted the critical SER195-HIS57 arrangement in the catalytic triad. Both DON and DRP-104, along with the reference drugs, induced strong cooperative intra-residue motion and bidirectional displacement in the PKa architecture. The results revealed favorable binding kinetics of DON/DRP-104, showing thermodynamic profiles that were either superior or comparable to those of the reference drugs. These findings support their consideration for clinical investigations into the management of carcinoma-associated HAE.

196

News (Medical) associated with Berotralstat Hydrochloride

04 Dec 2024

·www.globenewswire.com

BioCryst Reports Inducement Grants Under Nasdaq Listing Rule 5635(c)(4)

RESEARCH TRIANGLE PARK, N.C., Dec. 04, 2024 (GLOBE NEWSWIRE) -- BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) today announced that the compensation committee of BioCryst’s board of directors granted five newly-hired employees stock options to purchase an aggregate of 17,400 shares, and restricted stock units (RSUs) covering an aggregate of 12,150 shares, of BioCryst common stock. The options and RSUs were granted as of November 29, 2024, as inducements material to each employee entering into employment with BioCryst. The options and RSUs were granted in accordance with Nasdaq Listing Rule 5635(c)(4). The options have an exercise price of $7.50 per share, which is equal to the closing price of BioCryst common stock on the grant date. The options and RSUs vest in four equal annual installments beginning on the one-year anniversary of the grant date, in each case subject to the new employee’s continued service with the company. Each stock option has a 10-year term. The options and RSUs are subject to the terms and conditions of BioCryst’s Inducement Equity Incentive Plan and a stock option agreement or restricted stock unit agreement, as applicable, covering the grant. About BioCryst PharmaceuticalsBioCryst Pharmaceuticals is a global biotechnology company with a deep commitment to improving the lives of people living with hereditary angioedema and other rare diseases. BioCryst leverages its expertise in structure-guided drug design to develop first-in-class or best-in-class oral small-molecule and protein therapeutics to target difficult-to-treat diseases. BioCryst has commercialized ORLADEYO® (berotralstat), the first oral, once-daily plasma kallikrein inhibitor, and is advancing a pipeline of small-molecule and protein therapies. For more information, please visit www.biocryst.com or follow us on LinkedIn. BCRXW Contact:John Bluth+1 919 859 7910jbluth@biocryst.com

PROTACs

18 Nov 2024

·www.globenewswire.com

BioCryst Launches ORLADEYO® (berotralstat) in Ireland

RESEARCH TRIANGLE PARK, N.C., Nov. 18, 2024 (GLOBE NEWSWIRE) -- BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) today announced that the Health Services Executive (HSE) in Ireland has recommended ORLADEYO® (berotralstat) for the routine prevention of recurrent attacks of hereditary angioedema (HAE) in eligible patients 12 years and older. With this recommendation, HAE patients in Ireland will have access to the first oral, once-daily therapy for the reduction of recurrent HAE attacks. “The positive HSE recommendation of ORLADEYO broadens access to modern prophylaxis, providing greater choice for prescribing physicians and potentially a better quality of life for HAE patients in Ireland,” said Charlie Gayer, chief commercial officer of BioCryst. The HSE decision in Ireland follows the European Commission marketing authorization of ORLADEYO in April 2021. To date, ORLADEYO is licensed in 44 countries. About ORLADEYO® (berotralstat)ORLADEYO® (berotralstat) is the first and only oral therapy designed specifically to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years and older. One capsule of ORLADEYO per day works to prevent HAE attacks by decreasing the activity of plasma kallikrein. U.S. Indication and Important Safety Information INDICATIONORLADEYO® (berotralstat) is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 12 years and older. Limitations of useThe safety and effectiveness of ORLADEYO for the treatment of acute HAE attacks have not been established. ORLADEYO should not be used for the treatment of acute HAE attacks. Additional doses or dosages of ORLADEYO higher than 150 mg once daily are not recommended due to the potential for QT prolongation. IMPORTANT SAFETY INFORMATIONAn increase in QT prolongation was observed at dosages higher than the recommended 150 mg once-daily dosage and was concentration dependent. The most common adverse reactions (≥10% and higher than placebo) in patients receiving ORLADEYO were abdominal pain, vomiting, diarrhea, back pain, and gastroesophageal reflux disease. A reduced dosage of 110 mg taken orally once daily with food is recommended in patients with moderate or severe hepatic impairment (Child-Pugh B or C). Berotralstat is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein. P-gp inducers (eg, rifampin, St. John’s wort) may decrease berotralstat plasma concentration, leading to reduced efficacy of ORLADEYO. The use of P-gp inducers is not recommended with ORLADEYO. ORLADEYO at a dose of 150 mg is a moderate inhibitor of CYP2D6 and CYP3A4. For concomitant medications with a narrow therapeutic index that are predominantly metabolized by CYP2D6 or CYP3A4, appropriate monitoring and dose titration is recommended. ORLADEYO at a dose of 300 mg is a P-gp inhibitor. Appropriate monitoring and dose titration is recommended for P-gp substrates (eg, digoxin) when coadministering with ORLADEYO. The safety and effectiveness of ORLADEYO in pediatric patients <12 years of age have not been established. There are insufficient data available to inform drug-related risks with ORLADEYO use in pregnancy. There are no data on the presence of berotralstat in human milk, its effects on the breastfed infant, or its effects on milk production. To report SUSPECTED ADVERSE REACTIONS, contact BioCryst Pharmaceuticals, Inc. at 1-833-633-2279 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch/ Please see full Prescribing Information. The Irish Summary of Product Characteristics (SPC) and Patient Information Leaflet (PIL) for ORLADEYO (berotralstat) can be found through medicines.ie. Anyone can report suspected side effects to the HPRA. You can submit a report by visiting the HPRA’s reporting webpage to complete an online form hpra.ie/report. Adverse events should also be reported to BioCryst Pharmaceuticals at medinfoeurope@biocryst.com or +353 1 699 4405. About BioCryst Pharmaceuticals BioCryst Pharmaceuticals is a global biotechnology company with a deep commitment to improving the lives of people living with hereditary angioedema and other rare diseases. BioCryst leverages its expertise in structure-guided drug design to develop first-in-class or best-in-class oral small-molecule and protein therapeutics to target difficult-to-treat diseases. BioCryst has commercialized ORLADEYO® (berotralstat), the first oral, once-daily plasma kallikrein inhibitor, and is advancing a pipeline of small-molecule and protein therapies. For more information, please visit www.biocryst.com or follow us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements, including statements regarding BioCryst’s plans and expectations for ORLADEYO. These statements involve known and unknown risks, uncertainties and other factors which may cause BioCryst’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and are subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Some of the factors that could affect the forward-looking statements contained herein include: BioCryst’s ability to successfully implement or maintain its commercialization plans for ORLADEYO; risks related to government actions, including that decisions and other actions, including as they relate to pricing, may not be taken when expected or at all, or that the outcomes of such decisions and other actions may not be in line with BioCryst’s current expectations; the commercial viability of ORLADEYO, including its ability to achieve sustained market acceptance and demand; the FDA, HSE, or other applicable regulatory agency may require additional studies beyond the studies planned for products and product candidates, may not provide regulatory clearances which may result in delay of planned clinical trials, may impose certain restrictions, warnings, or other requirements on products and product candidates, may impose a clinical hold with respect to product candidates, or may withhold, delay or withdraw market approval for products and product candidates; BioCryst’s ability to successfully manage its growth and compete effectively; and risks related to the international expansion of BioCryst’s business. Please refer to the documents BioCryst files periodically with the Securities and Exchange Commission, specifically BioCryst’s most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K, which identify important factors that could cause actual results to differ materially from those contained in BioCryst’s projections and forward-looking statements. BCRXW Contact: John Bluth+1 919 859 7910jbluth@biocryst.com Niamh Lyons+353 87 639 7083nlyons@biocryst.com

Drug Approval

06 Nov 2024

·www.globenewswire.com

BioCryst to Present at Upcoming Investor Conferences

RESEARCH TRIANGLE PARK, N.C., Nov. 06, 2024 (GLOBE NEWSWIRE) -- BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) today announced that the company plans to present at the following conferences: 2024 Jefferies London Healthcare Conference on Wednesday, November 20, 2024, at 5:00 a.m. ET.7th Annual Evercore HealthCONx Conference in Coral Gables on Wednesday, December 4, 2024, at 2:35 p.m. ET.Piper Sandler 36th Annual Healthcare Conference in New York on Thursday, December 5, 2024, at 8:30 a.m. ET. Links to the live audio webcasts and replays of the presentations may be accessed in the Investors & Media section of BioCryst’s website at http://www.biocryst.com. About BioCryst Pharmaceuticals BioCryst Pharmaceuticals is a global biotechnology company with a deep commitment to improving the lives of people living with hereditary angioedema and other rare diseases. BioCryst leverages its expertise in structure-guided drug design to develop first-in-class or best-in-class oral small-molecule and protein therapeutics to target difficult-to-treat diseases. BioCryst has commercialized ORLADEYO® (berotralstat), the first oral, once-daily plasma kallikrein inhibitor, and is advancing a pipeline of small-molecule and protein therapies. For more information, please visit www.biocryst.com or follow us on LinkedIn. BCRXW Contact:John Bluth+1 919 859 7910jbluth@biocryst.com

100 Deals associated with Berotralstat Hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
D11673 D11674	-	B06AC	DB15982

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hereditary Angioedema	US	BioCryst Pharmaceuticals, Inc.	03 Dec 2020

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hereditary Angioedema Types I and II	Phase 3	US	BioCryst Pharmaceuticals, Inc.	16 Feb 2018
Hereditary Angioedema Types I and II	Phase 3	AU	BioCryst Pharmaceuticals, Inc.	16 Feb 2018
Hereditary Angioedema Types I and II	Phase 3	DK	BioCryst Pharmaceuticals, Inc.	16 Feb 2018
Hereditary Angioedema Types I and II	Phase 3	DE	BioCryst Pharmaceuticals, Inc.	16 Feb 2018
Hereditary Angioedema Types I and II	Phase 3	IL	BioCryst Pharmaceuticals, Inc.	16 Feb 2018
Hereditary Angioedema Types I and II	Phase 3	IT	BioCryst Pharmaceuticals, Inc.	16 Feb 2018
Hereditary Angioedema Types I and II	Phase 3	ES	BioCryst Pharmaceuticals, Inc.	16 Feb 2018
Hereditary Angioedema Types I and II	Phase 3	CH	BioCryst Pharmaceuticals, Inc.	16 Feb 2018
Hereditary Angioedema Types I and II	Phase 3	GB	BioCryst Pharmaceuticals, Inc.	16 Feb 2018

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ACAAI2024 Manual	Not Applicable	Hereditary Angioedema	353	Berotralstat (HAE-nl-C1-INH)	yeohjypzrh(mubdffnwsr) = vhujmerwkm anwxgwbnpq (kqdjgaqwjt ) View more	Positive	24 Oct 2024
ACAAI2024 Manual	Not Applicable	Hereditary Angioedema	257	Berotralstat	wwlfluonog(lckqflalkv) = poczlietyo zrshkggnxb (upwuhjodju ) View more	Positive	24 Oct 2024
				Lanadelumab	wwlfluonog(lckqflalkv) = rubznvscfe zrshkggnxb (upwuhjodju ) View more
ACAAI2024 Manual	Not Applicable	Hereditary Angioedema	466	Berotralstat (patients with C1-inhibitor deficiency)	jyaejbjtxj(igftzzszlu) = fbbcrhyjvh fvzkxuscjp (fbdsmstiub ) View more	Positive	24 Oct 2024
ACAAI2024	Not Applicable	Hereditary Angioedema	357	Berotralstat	lnyeefjpmt(jnmjgomqjk) = kwssoyiptd mgcbaumnil (ffzqdgjgtj )	Positive	24 Oct 2024
				Lanadelumab	lnyeefjpmt(jnmjgomqjk) = rtzamqzlcp mgcbaumnil (ffzqdgjgtj )
Optime Care Specialty Pharmacy (ACAAI2024)	Not Applicable	Hereditary Angioedema C1-inhibitor levels/function within normal laboratory reference range(s)-	353	Berotralstat	gshjwylivs(ptfivoyfkd) = flmvtgnmzb xwbyhnxlyo (uqqbozzzjs, -3.10 to -1.85)	Positive	24 Oct 2024
ACAAI2024	Not Applicable	Hereditary Angioedema C1-inhibitor deficiency-	466	Berotralstat	dcncrexqrn(johgmjfjdo) = cienewqayr utmzkkyouc (apspxciczc, -1.92 to -1.18)	Positive	24 Oct 2024
GlobeNewswire Manual	Not Applicable	Hereditary Angioedema	260	ORLADEYO® (berotralstat)	tokisvgfvi(azfzacfbnr) = psmixjqlfc gaiwnauesw (kaxvrejmak ) View more	Positive	09 May 2024
				ORLADEYO® (berotralstat) (long-term prophylaxis)	tokisvgfvi(azfzacfbnr) = xczyqvqpel gaiwnauesw (kaxvrejmak ) View more
NCT03873116 (APeX-J, Pubmed \| World Allergy Organ J)	Phase 3	Hereditary Angioedema	17	Berotralstat 150 mg	witgunrlhi(dwafbazxik) = hxovfodkna qnyysqyham (atubrzvetk, 0.09) View more	Positive	01 Mar 2024
AAAAI2024	Not Applicable	Hereditary Angioedema Type III First line C1-inhibitor deficiency	-	Berotralstat (HAE-C1INH)	vljfbworbj(tqewvnrrgb) = pglwmrcwxt ypycxjruun (foeuisagbf, 0.33 - 3.33) View more	Positive	23 Feb 2024
				Berotralstat (HAE-nl-C1INH)	vljfbworbj(tqewvnrrgb) = luqnzngocy ypycxjruun (foeuisagbf, 1.33 - >3.33) View more
AAAAI2024	Not Applicable	HAE Type I/II	335	Berotralstat 110 mg	wazktfxrhx(kcxpqpprsd) = irxajkfbwr afpmrnwdbg (zjsvayrjrr )	Positive	23 Feb 2024
				Berotralstat 150 mg	wazktfxrhx(kcxpqpprsd) = hdrkggeijk afpmrnwdbg (zjsvayrjrr )

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