- |||||||||| Vyjuvek (beremagene geperpavec) / Krystal Biotech
Review, Journal, Gene therapy: Emerging Gene Therapeutics for Epidermolysis Bullosa under Development. (Pubmed Central) - Feb 28, 2024
The clinically more advanced gene replacement strategy was successfully applied in severe EB forms, leading to a ground-breaking in vivo gene therapy product named beremagene geperpavec (B-VEC) recently approved from the US Food and Drug Administration (FDA). In addition, the continuous innovations in both designer nucleases and gene editing technologies enable the efficient and potentially safe repair of mutations in EB in a potentially permanent manner, inspiring researchers in the field to define and reach new milestones in the therapy of EB.
- |||||||||| KB408 / Krystal Biotech
Murine Toxicology Study of Repeat-Dose Inhaled KB408, an HSV-1-Based Vector for the Treatment of Alpha-1 Antitrypsin Deficiency (San Diego Convention Center, Area F (Hall A-B2, Ground Level)) - Feb 20, 2024 - Abstract #ATS2024ATS_4208;
KB407 is able to transduce and deliver full-length CFTR to clinically relevant airway epithelial cell populations in vitro, including patient-derived apical-out organoids, supporting future clinical development of KB407 as an inhaled therapeutic for patients with CF. KB408 showed no adverse effects and limited biodistribution when delivered via inhalation to mice, supporting the initiation of a first-in-human Phase 1 single ascending dose study.
- |||||||||| Vyjuvek (beremagene geperpavec) / Krystal Biotech
Journal, Gene therapy: Ocular Gene Therapy in a Patient with Dystrophic Epidermolysis Bullosa. (Pubmed Central) - Feb 7, 2024
Beremagene geperpavec (B-VEC) is a replication-deficient herpes simplex virus type 1-based gene therapy engineered to deliver functional human type VII collagen. Here, we report the case of a patient with cicatrizing conjunctivitis in both eyes caused by dystrophic epidermolysis bullosa who received ophthalmic administration of B-VEC, which was associated with improved visual acuity after surgery.
- |||||||||| KB408 / Krystal Biotech
Enrollment open: Serpentine-1: A Study of KB408 for the Treatment of Alpha-1 Antitrypsin Deficiency (clinicaltrials.gov) - Feb 6, 2024
P1, N=12, Recruiting,
Here, we report the case of a patient with cicatrizing conjunctivitis in both eyes caused by dystrophic epidermolysis bullosa who received ophthalmic administration of B-VEC, which was associated with improved visual acuity after surgery. Not yet recruiting --> Recruiting
- |||||||||| Vyjuvek (beremagene geperpavec) / Krystal Biotech
Journal: Estimated Spending on Beremagene Geperpavec for Dystrophic Epidermolysis Bullosa. (Pubmed Central) - Jan 31, 2024
Estimated lifetime total costs per patient were $15 million (range, $10 million-$20 million) per patient with autosomal recessive DEB and $17 million (range, $11 million-$22 million) for patients with autosomal dominant DEB. Results of this economic evaluation suggest that the FDA's broad indication for the use of B-VEC in treating both autosomal recessive and autosomal dominant DEB will have significant implications for payers.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen, Vyjuvek (beremagene geperpavec) / Krystal Biotech
Preclinical, Journal, Gene therapy: Attenuated Replication-Competent Herpes Simplex Virus Expressing an ECM-Modifying Transgene Hyaluronan Synthase 2 of Naked Mole Rat in Oncolytic Gene Therapy. (Pubmed Central) - Nov 25, 2023
Another HSV-based drug, beremagene geperpavec (B-VEC), received approval in 2023 to treat the rare genetic disease dystrophic epidermolysis bullosa, and was also the first clinically approved HSV vector carrying an extracellular matrix (ECM)-modifying transgene...The viral replication, transgene expression and cytotoxic effect of the novel vector was studied in glioma cells. Our results show that an attenuated, replication-competent HSV vector expressing a foreign ECM-modifying transgene, namely HAS2, provides an effective tool to study and combat cancer in humans.
- |||||||||| Vyjuvek (beremagene geperpavec) / Krystal Biotech
Journal, Gene therapy: Herpes simplex virus gene therapy for dystrophic epidermolysis bullosa (DEB). (Pubmed Central) - Aug 23, 2023
This represents a giant step, not only toward the treatment of this devastating disease, but also for the whole field of non-replicative (nr) recombinant HSV-1 vectors for gene therapy. To view this Bench to Bedside, open or download the PDF.
- |||||||||| Vyjuvek (beremagene geperpavec-svdt) / Krystal Biotech
Trial completion, Trial completion date, Trial primary completion date: A Long-term Treatment With B-VEC for Dystrophic Epidermolysis Bullosa (clinicaltrials.gov) - Aug 18, 2023
P3, N=47, Completed,
To view this Bench to Bedside, open or download the PDF. Enrolling by invitation --> Completed | Trial completion date: Dec 2023 --> Jul 2023 | Trial primary completion date: Dec 2023 --> Jul 2023
- |||||||||| KB407 / Krystal Biotech
Enrollment change, Trial withdrawal: A Study of Inhaled KB407 for the Treatment of Cystic Fibrosis (clinicaltrials.gov) - Aug 14, 2023
P1, N=0, Withdrawn,
Enrolling by invitation --> Completed | Trial completion date: Dec 2023 --> Jul 2023 | Trial primary completion date: Dec 2023 --> Jul 2023 N=13 --> 0 | Recruiting --> Withdrawn
- |||||||||| KB407 / Krystal Biotech
Enrollment change, Trial completion date, Trial primary completion date: CORAL-1: A Study Assessing KB407 for the Treatment of Cystic Fibrosis (clinicaltrials.gov) - Jul 28, 2023
P1, N=12, Recruiting,
N=13 --> 0 | Recruiting --> Withdrawn N=20 --> 12 | Trial completion date: Mar 2024 --> Jul 2024 | Trial primary completion date: Mar 2024 --> Jul 2024
- |||||||||| Vyjuvek (beremagene geperpavec) / Krystal Biotech
Review, Journal: Beremagene Geperpavec: First Approval. (Pubmed Central) - Jul 24, 2023
A Marketing Authorization Application for beremagene geperpavec in Europe is planned for the second half of 2023. This article summarizes the milestones in the development of beremagene geperpavec leading to this first approval for dystrophic epidermolysis bullosa.
- |||||||||| KB407 / Krystal Biotech
Enrollment open, Trial initiation date: CORAL-1: A Study Assessing KB407 for the Treatment of Cystic Fibrosis (clinicaltrials.gov) - Jun 5, 2023
P1, N=20, Recruiting,
This article summarizes the milestones in the development of beremagene geperpavec leading to this first approval for dystrophic epidermolysis bullosa. Not yet recruiting --> Recruiting | Initiation date: Nov 2022 --> Jun 2023
- |||||||||| Vyjuvek (beremagene geperpavec-svdt) / Krystal Biotech
Enrollment status, Enrollment change, Trial completion date, Trial primary completion date: A Long-term Treatment With B-VEC for Dystrophic Epidermolysis Bullosa (clinicaltrials.gov) - Apr 18, 2023
P3, N=45, Enrolling by invitation,
Not yet recruiting --> Recruiting | Initiation date: Nov 2022 --> Jun 2023 Recruiting --> Enrolling by invitation | N=30 --> 45 | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023
- |||||||||| KB301 / Krystal Biotech
Enrollment open, Enrollment change, Trial completion date, Trial primary completion date: PEARL-1: A Phase I Study of KB301, a Replication-Incompetent, Non-Integrating Vector Expressing Human Type III Collagen (COL3) for the Treatment of Superficial Skin Depressions (clinicaltrials.gov) - Apr 12, 2023
P1, N=64, Recruiting,
Recruiting --> Enrolling by invitation | N=30 --> 45 | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023 Active, not recruiting --> Recruiting | N=44 --> 64 | Trial completion date: Jun 2027 --> May 2028 | Trial primary completion date: Sep 2022 --> Aug 2023
- |||||||||| Vyjuvek (beremagene geperpavec-svdt) / Krystal Biotech
Trial completion, Phase classification: GEM-1: A Phase I/II Study of KB103, a Topical HSV1-COL7, on DEB Patients (clinicaltrials.gov) - Jan 31, 2023
P1/2, N=12, Completed,
In these two case reports, continued wound healing and evidence of systemic improvement were observed with long-term administration of B-VEC without significant related adverse events. Active, not recruiting --> Completed | Phase classification: P2 --> P1/2
- |||||||||| Vyjuvek (beremagene geperpavec) / Krystal Biotech
Clinical, Clinical Trial,Phase III, Journal: Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa. (Pubmed Central) - Dec 16, 2022
P3
Longer and larger trials are warranted to determine the durability and side effects of B-VEC for this disease. (Funded by Krystal Biotech; GEM-3 ClinicalTrials.gov number, NCT04491604.).
- |||||||||| KB301 / Krystal Biotech
Enrollment closed, Trial completion date, Trial primary completion date: PEARL-1: A Phase I Study of KB301, a Replication-Incompetent, Non-Integrating Vector Expressing Human Type III Collagen (COL3) for the Treatment of Superficial Skin Depressions (clinicaltrials.gov) - Dec 15, 2022
P1, N=44, Active, not recruiting,
(Funded by Krystal Biotech; GEM-3 ClinicalTrials.gov number, NCT04491604.). Recruiting --> Active, not recruiting | Trial completion date: Jan 2022 --> Jun 2027 | Trial primary completion date: Nov 2021 --> Sep 2022
- |||||||||| KB407 / Krystal Biotech
Respiratory cell-type affinity and absolute CFTR expression in the primate airway upon nebulization of KB407 (119 A) - Aug 5, 2022 - Abstract #NACFC2022NACFC_448;
Recruiting --> Active, not recruiting | Trial completion date: Jan 2022 --> Jun 2027 | Trial primary completion date: Nov 2021 --> Sep 2022 Taken together, these data indicate that KB407 capablytransduces multiple cell types that contribute to native CFTR function inprimate airways and expresses the transgene at physiologically relevantlevels, providing further support for the potential of KB407 as an inhalablegene therapy for the treatment of CF.
- |||||||||| Vyjuvek (beremagene geperpavec-svdt) / Krystal Biotech
Trial completion, Trial completion date: GEM-3: Ph 3 Efficacy and Safety of B-VEC for the Treatment of DEB (clinicaltrials.gov) - Aug 3, 2022
P3, N=31, Completed,
Taken together, these data indicate that KB407 capablytransduces multiple cell types that contribute to native CFTR function inprimate airways and expresses the transgene at physiologically relevantlevels, providing further support for the potential of KB407 as an inhalablegene therapy for the treatment of CF. Active, not recruiting --> Completed | Trial completion date: Oct 2021 --> Jan 2022
- |||||||||| KB407 / Krystal Biotech
Enrollment open, Trial completion date, Trial initiation date, Trial primary completion date: A Study of Inhaled KB407 for the Treatment of Cystic Fibrosis (clinicaltrials.gov) - Jun 8, 2022
P1, N=13, Recruiting,
Active, not recruiting --> Completed | Trial completion date: Oct 2021 --> Jan 2022 Not yet recruiting --> Recruiting | Trial completion date: May 2022 --> Oct 2024 | Initiation date: Oct 2021 --> Mar 2022 | Trial primary completion date: Mar 2022 --> Jul 2024
- |||||||||| KB105 / Krystal Biotech
Enrollment closed, Trial primary completion date, Gene therapy: Topical KB105 Gene Therapy for the Treatment of TGM1-deficient Autosomal Recessive Congenital Ichthyosis (ARCI) (clinicaltrials.gov) - Sep 12, 2021
P1/2, N=6, Active, not recruiting,
Overall, our results demonstrate that rescuing TGM1 deficiency in ARCI patients via topical KB105 application represents a promising strategy for safely and non-invasively treating this debilitating disease. Recruiting --> Active, not recruiting | Trial primary completion date: Mar 2020 --> Oct 2022
- |||||||||| Dovonex (calcipotriol) / Leo Pharma, Novartis
[VIRTUAL] Engineered Herpes Simplex Virus Type 1 (HSV-1)-Based Vectors as a Platform for Localized Delivery of Therapeutic Antibodies in the Treatment of Skin Disorders () - Apr 30, 2021 - Abstract #ASGCT2021ASGCT_822;
P1/2, P3
(Krystal) has leveraged its HSV-1-based STAR-D (Skin-Targeted Delivery) platform to deliver therapeutic transgenes to patients with debilitating diseases, including vectors beremagene geperpavec (“B-VEC”) - encoding human COL7A1 for the treatment of dystrophic epidermolysis bullosa (ClinicalTrials.gov Identifier: NCT04491604), and KB105 - encoding human TGM1 for the treatment of autosomal recessive congenital ichthyosis (Clinicaltrials.gov Identifier: NCT04047732)...To evaluate the ability of a vector-encoded antibody to reduce an AD-like phenotype on a macro-scale, KB502 was applied topically in an MC903-induced murine model of AD...At this time, Krystal has expanded its STAR-D-based antibody portfolio to at least 12 unique products, including vectors expressing anti-CD20, anti-IL-17, and anti-CCR4 antibodies. The studies described herein warrant the further investigation of STAR-D as a platform for localized delivery of therapeutic antibodies, including for the treatment of diseases of skin and other organ systems amenable to immunomodulatory therapeutics.
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