Monthly Archives: June 2022

Efficacy and Safety of Sintilimab in Combination with Concurrent Chemo | CMAR – Dove Medical Press

Posted: June 22, 2022 at 2:40 am

Introduction

Gastric and gastroesophageal junction (G/GEJ) cancer is the fifth most common cancer and the third most deadly cancer worldwide, with an estimated 1 million new cases and 783,000 death in 2018.1 In China, the incidence and mortality rate of G/GEJ cancer is substantially higher than that of the rest of the world. According to the data from Cancer Registry in China, the country has about 403,000 new cases and 291,000 death each year. Moreover, about 54% of patients are diagnosed with locally advanced (stage II and III) G/GEJ cancers2 which are characterized by tumor infiltration of the serosa and the presence of regional lymph node metastasis. At this stage, surgery alone might not be sufficient, and even with R0 surgical resection, the prognosis remains dismal.3 Regarding the patients developing T3-4 and N2-3 cancer, the 5-year survival rate after surgery is lower than 15%.4

Multimodality regimens, such as perioperative chemotherapy and adjuvant or neoadjuvant concurrent chemoradiotherapy (cCRT), have been developed to improve the poor prognosis in advanced G/GEJ cancers. Clinical trials have demonstrated that perioperative chemotherapy has specific advantages in degrading tumor stage, increasing R0 resection rate, and improving pathological complete response (pCR) rate. Thus, patients with operable stage III to IVa G/GEJ cancers can obtain significant survival benefits.57 The therapeutic benefits of preoperative cCRT, on the other hand, have been confirmed by the long-term follow-up results from CROSS and POET trials.8,9 In addition, the multidisciplinary team (MDT) guided cCRT has dominated the treatment for stage IIIIV inoperable tumors in western countries, which provides a therapeutic window for radical surgery to extend the overall survival.

In addition to surgery, chemotherapy and radiation therapy, immunotherapy has become a new pillar of cancer therapy, improving the prognosis across a wide variety of solid tumors. One main driver behind this success is the development of immune checkpoint inhibitors (ICIs). Immunotherapy targeting PD-1/PD-L1 signalling is the most widely investigated regimen, and emerging clinical evidence has demonstrated its efficacy and safety. As a monotherapy regimen, anti-PD-(L)1 has conferred an approximately 12% objective response rate (ORR) in patients with advanced G/GEJ cancers, and an overall survival benefit was noted.1012 In particular, the ORR in PD-L1 positive tumors was reported to be 15.5% versus 5.5% in PD-L1 negative ones in the KEYNOTE-059 study. Based on such results, in 2017 the US Food and Drug Administration (FDA) approved the use of pembrolizumab in the third-line treatment for patients with recurrent or advanced gastric cancer whose tumors express PD-L1. Also, in 2017 the Japanese Ministry of Health, Labor and Welfare approved nivolumab for the treatment of unresectable recurrent or advanced gastric cancer, which has progressed after chemotherapy.

Enormous combination studies have been carried out to improve the anti-tumor activities of the anti-PD-(L)1 regimen. In addition to inhibiting tumor proliferation, chemotherapy can modulate the immune system by enhancing tumor antigenicity, disturbing immune-suppressive pathways, inducing immunogenic cell death, and increasing effector T-cell functions.13,14 Therefore, it is hypothesized that the addition of chemotherapy to anti-PD-(L)1 may render superior benefits in advanced G/GEJ cancer patients. The global Phase 3 trial CHECKMATE-649 demonstrated a significant improvement in PFS (7.7 months versus 6.0 months in chemotherapy alone cohort) and OS (14.4 months versus 11.1 months in chemotherapy alone cohort) by combining chemotherapy with anti-PD-(L)1.15,16 As a result of this study, in April 2021 FDA approved nivolumab in combination with chemotherapy as the first-line treatment for advanced or metastatic G/GEJ and esophageal adenocarcinoma. Likewise, in the ongoing ATTRACTION-4 trials, nivolumab combined with chemotherapy has shown encouraging clinical activity in first-line treatment in Asian patients with advanced G/GEJ, with improved PFS and ORR and favourable safety profile.17

On the other hand, irradiation activates host immunity by triggering immunogenic cell death to release the damage-associated molecular patterns (DAMPs), which leads to dendritic cell activation, tumor antigens presentation and antigen-specific T cells priming.18 Based on the insights gained, there is a strong rationale to support the use of PD-(L)1 inhibitors with cCRT to convert the cold tumors into hot tumors. The therapeutic efficacy of such regimen has been demonstrated in the Phase III PACIFIC trial of the PD-L1 inhibitor durvalumab in locally advanced, unresectable NSCLC following platinum-based cCRT.19 Compared to the placebo, an improved PFS (from 5.6 to 16.8 months) with a similar safety profile was noted with durvalumab, and its efficacy was irrespective of tumor PD-L1 status. Based on that, in 2018 FDA approved durvalumab for patients with unresectable stage III NSCLC whose disease has not progressed following platinum-based cCRT. Moreover, the phase 3 CHECKMATE-577 trial is the first study to evaluate a checkpoint inhibitor in the adjuvant setting after cCRT and has demonstrated a statistically significant improvement in disease-free survival (DFS) from 11.0 months to 22.4 months in patients with resected esophageal and GEJ cancers.20 Despite these advances, the ideal combination regimen of checkpoint inhibitors and cCRT is yet to be optimized in patients with advanced G/GEJ cancers.

Sintilimab is a highly selective, monoclonal IgG4 antibody that inhibits interactions between PD-1 and its ligands, with a robust anti-tumor response.21 In vitro, compared to nivolumab or pembrolizumab, sintilimab has a higher binding affinity and is able to bind with more PD-1 molecules on CD3+T cells, and has better T cell activating characteristics.21 In a phase 1b study (NCT03745170), sintilimab combined with oxaliplatin/capecitabine has shown promising efficacy in gastric cancer with an ORR of 85%22 which warranted a phase 3 ORIENT-16 study (NCT03745170) to further investigate the therapeutic potential of sintilimab in combination with chemotherapy in patients with advanced G/GEJ cancers.23 The interim results from ORIENT-16 study were orally presented on 2021 ESMO, in which sintilimab was demonstrated to be the first PD-1 inhibitor to show superior OS and PFS with an acceptable safety profile, in combination with chemo, in Chinese patients with G/GEJ cancer regardless of PD-L1 expression status.24

In addition, in Japan, D2 gastrectomy plus adjuvant S-1 is the standard treatment for locally advanced gastric cancer [18, 19], while nab-paclitaxel (nab-PTX) is an approved second-line gastric cancer treatment [23, 24]. The combination of S-1 with nab-PTX has proven to be an effective and safe first-line regimen in clinical [25, 26]. Furthermore, the interim analysis from the JACCRO GC-07 trial has demonstrated that the postoperative S-1 plus docetaxel is effective with few safety concerns in patients with stage III gastric cancer25 and similar benefits were also noted with S-1 plus nab-PTX in untreated patients with metastatic gastric cancer.26

Therefore, we propose to conduct the SHARED (Sintilimab plus chemoradiotherapy in gastric and GEJ adenocarcinoma) study, a phase 2 trial designed to evaluate perioperative sintilimab combined cCRT (S-1 plus nab-PTX) for patients with locally advanced G/GEJ adenocarcinoma.

The primary objective is to demonstrate whether adding sintilimab to cCRT (a combination of nab-PTX and S-1 with radiotherapy) improves pathological complete response (pCR) rate in patients with locally advanced G/GEJ adenocarcinoma. The secondary objectives include disease-free survival (DFS), major pathological response (MPR), R0 resection rate, surgical adverse events (AEs), overall survival (OS), event-free survival (EFS), and safety profile. Moreover, the prognostic value of tumor biomarkers and immune biomarkers will be evaluated.

This is a prospective, multicentre, single-arm phase II trial in China. Eligible patients are aged 18 or older, histological or cytological confirmed locally advanced gastric or GEJ adenocarcinoma as defined according to 8th edition of American Joint Committee on Cancer (AJCC) classification of malignant tumors, a clinical-stage of III to IVa (T3N2-3M0, T4aN+M0 or T4bNanyM0) according to the 8th edition of Tumor, Node, Metastasis (TNM) classification, an Eastern Cooperative Oncology Group performance (ECOG) score 1, no prior cancer treatment, and one or more measurable lesions based on Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

Eligibility criteria on physiological parameters and organ function included adequate haematological function (absolute neutrophil count [ANC] 1.5109/L, platelet count [PLT] 100109/L, haemoglobin [Hb] 90 g/L, international normalized ratio (INR)/prothrombin time (PT) 1.5upper limit of normal [ULN], and activated partial thromboplastin time (aPTT) 1.5ULN), adequate hepatic function (plasma total bilirubin [PTB] 1.5ULN, alanine transaminase [ALT], aspartate transaminase [AST] and alkaline phosphatase [AKP] concentration 2.5ULN), and adequate renal function (creatinine concentration 1ULN, albumin concentration 30g/L).

Pregnant, breastfeeding women or those positive in baseline pregnancy tests are not eligible, and all female patients will be on contraception during the study. Other exclusion criteria include patients diagnosed with gastric neuroendocrine tumors; patients with distant metastasis according to computed CT/MRI or endoscopic ultrasound (EUS); history of chemotherapy, radiotherapy or immunotherapy; patients with active malignant tumor in recent 5 years, except for basal cell or squamous cell cancer, superficial bladder cancer, and in-situ cervical or breast carcinoma; uncontrollable pleural effusion, pericardial effusion or ascites; severe cardiovascular disease within 12 months before recruitment, including coronary artery disease, grade 2 congestive heart failure, uncontrollable arrhythmias and myocardial infarction; patients with upper GI tract obstruction/bleeding or functional abnormality or malabsorption syndrome, which can affect absorption of S-1; uncontrollable concurrent infection and other concomitant diseases systemic diseases, or moderate or severe renal injury; allergic to any drug in this study; use of steroids or any other systemic immunosuppressive agents within 14 days before recruitment; use of corticosteroids (dosage >10mg/d prednisone or equivalent dose of other glucocorticoids) or other immunosuppressive agents within 4 weeks before recruitment, except patient treated with hormone for preventing allergy to contrast agents; receiving treatment from other studies within 4 weeks before recruitment; patients with autoimmune diseases or primary immunodeficiency; vaccinated with attenuated vaccine within 4 weeks before recruitment or plan to vaccinate during the study; active infections, including TB, HIV, HBV and HCV; and history of allogeneic stem cell transplantation or organ transplantation.

The study protocol and the informed consent forms have been reviewed and approved by institutional review boards and ethics committees at each institution. The study will be done in accordance with the Declaration of Helsinki and Good Clinical Practice Guidelines, and the written informed consent will be obtained from all enrolled patients. The study has been registered (ChiCTR1900024428).

All patients will start with one cycle (3 weeks) of induction chemotherapy of S-1 (40mg/m2, PO, bid, D1 to D14) and nab-PTX (100120mg/m2, IV, D1 and D8) in combination with sintilimab (200mg, IV, D1), followed by radiation therapy (45Gy/1.8Gy in 25 factions) with concurrent nab-PTX (80100 mg/m2, IV, D1, D8, D15, and D22) and sintilimab (200mg, IV, D1 and D22) for 5 weeks. One to three weeks after the completion, patients will receive another cycle (3 weeks) of S-1 (40mg/m2, PO, bid, D1 to D14) and nab-PTX (100120mg/m2, IV, D1 and D8) in combination with sintilimab (200mg, IV, D1). All patients will be preferably operated on within 1 to 3 weeks later. In case of any treatment-related adverse event (TRAE) that cannot be resolved shortly is noted, the patient will be urged to tumor assessment followed by the surgery. The adjuvant therapy will start in 46 weeks after the operation with 3 cycles (3 weeks) of S-1 (40mg/m2, PO, bid, D1 to D14 of each cycle), nab-PTX (100120mg/m2, IV, D1 and D8 of each cycle) and sintilimab (200mg, IV, D1 of each cycle). Schematic diagram of SHARED regimen is in Figure 1.

Figure 1 Schematic diagram of SHARED regimen. All patients will receive one cycle of S-1 (40mg/m2, PO, Bid, D1 to D14) and nab-PTX (100120mg/m2, IV, D1 and D8) in combination with sintilimab (200mg, IV, D1) for 3 weeks, followed by radiation therapy (45Gy/1.8Gy in 25 factions) with nab-PTX (80100 mg/m2, IV, D1, D8, D15, and D22) and sintilimab (200mg, IV, D1 and D22) for 5 weeks. One to three weeks after the completion, patients will receive one cycle of S-1 (40mg/m2, PO, Bid, D1 to D14) and nab-PTX (100120mg/m2, IV, D1 and D8) in combination with sintilimab (200mg, IV, D1). All patients will be operated on within 1 to 3 weeks later. The adjuvant therapy will start in 46 weeks after the operation with 3 cycles (3 weeks) of S-1 (40mg/m2, PO, Bid, D1 to D14 of each cycle), nab-PTX (100120mg/m2, IV, D1 and D8 of each cycle) and sintilimab (200mg, IV, D1 of each cycle).

Dose modification of sintilimab is not allowed in this study. Sintilimab will be withheld to manage intolerable adverse event until toxicity resolves. Corticosteroids will be used to manage immune-related adverse events (irAEs) with Sintilimab discontinuation allowed for no more than 12 weeks. Sintilimab will be terminated upon completion of treatment, disease progression or intolerance. Guidance for sintilimab delay or discontinuation after adverse events is in Table 1.

Table 1 Guidance for Sintilimab Delay or Discontinuation

Before the operation, all patients will be assessed by the multidisciplinary committee, and surgical protocol will be decided according to the clinical judgment. A subject must be withdrawn from the study if a disease progression is noted. The surgical protocol includes transthoracic esophagectomy with resection of the proximal stomach and mediastinal and abdominal lymphadenectomy for type 1 GEJ cancers and gastrectomy with transhiatal distal oesophagectomy plus D2 lymphadenectomy for types 2 and 3 GEJ cancers. For the patients with gastric cancer, total or subtotal distal gastrectomy with D2 lymphadenectomy will be performed. For inoperable patients, the treatment options will be evaluated and tailored to the context of the patients situation and needs. Exploratory laparoscopy will be conducted to exclude peritoneal metastases, if necessary.

During the study, all patients will be assessed by physical examination, weight, ECOG performance status, vital signs, routine laboratory tests (blood routine, blood chemistry, blood coagulation routine, urine routine, stool routine for occult blood, and thyroid function), and 12-lead electrocardiogram (ECG) within 7 days before day one of the first cycle, one day before day one in subsequent cycles, one day before the surgery, one day after study completion or withdrawal, and at the first follow-up visit. Besides, all patients will be examined by echocardiography within 7 days before starting the study, one day before the surgery, one day before the first adjuvant cycle, and one day after study completion or withdrawal.

Tumor assessment by means of computed CT/MRI and EUS will be done at baseline (within 4 weeks before enrolment), every six weeks (7 days) perioperatively, every nine weeks (7 days) postoperatively, and every 3 months until the development of disease progression or the start of new anticancer treatment after treatment completion.

All patients will be followed up on a monthly basis in the first 3 months for safety, and telephone visits will be conducted after the first in-person hospital visit. After completing safety follow-up, monthly telephone visits for a maximum of 2 years will be implemented until death from any cause, lost to follow-up, consent withdrawal, or sponsors election to terminate the study prematurely.

The primary endpoint is the rate of pCR, which is defined as the absence of viable tumor cells assessed by histological evaluation criteria after preoperative therapy.

DFS is defined as the time to postoperative recurrence or death from any cause. OS is defined as the time interval from enrolment to all-caused death. EFS is defined as the time from enrolment to recurrence or death from any cause. Patients (including those lost to follow-up) still alive at the time of analysis (DFS, OS and EFS) will be censored at the last disease assessment date.

MPR is defined as tumor residual cells 10% in the surgical specimen. R0 resection rate is defined as the rate of the complete surgical removal of any residual cancer cells in the tumor bed.

Adverse events (AEs) will be monitored and graded according to the US National Cancer Institutes Common Terminology Criteria for Adverse Events (NCI CTCAE, version 4.03). All AEs will be recorded from the first dose of the study drug until 90 days after the last dose of the study drugs. Serious adverse events (SAEs) are defined as death, hospitalization or prolonged hospitalization, permanent or severe disability, teratogenesis, or other significant clinical sequels. Surgical AEs are defined as the complication which happens during or in 30 days after the operation.

Exploratory endpoints are assessments of potential tumor biomarkers and the relationship between immune biomarkers and clinical response.

Peripheral blood samples (10ml) will be collected at baseline and on the same day of sintilimab administration to evaluate serum levels of related tumor biomarkers (eg, CEA, AFP, CA19-9, CA72-4, and CA24-2).

Tumor tissue samples will be collected at baseline and intrasurgery. TMB and MSI will be measured by FoundationOne CDx assay (Foundation Medicine, Cambridge, MA, USA). TMB-H will be defined as 10mut/Mb, and MSI-H will be defined as more than 30% of markers show instability in marker panels. PD-L1 expression will be measured by 22C3 pharmaDx assay (Agilent Technologies, Carpinteria, CA, USA), and PD-L1+ will be defined as PD-L1 CPS 1%. HER2 immunohistochemistry was performed on the BenchMark XT platform (Ventana Medical Systems, Tucson, AZ, USA) according to the manufacturers recommendation. Normal gastric tissue will be collected concomitantly from each patient, and whole-exome sequencing (WES) will be performed to compare the transcriptome between tumor tissue and normal gastric tissue.

For the purpose of study design, a pCR rate at 15% (H0) in this setting will not be viewed as compelling for further study, while a pCR rate at 35% (Ha) or more will be considered of interest for further investigation. Based on this, a Simon optimal two-stage design will be employed with an H0=0.15 vs Ha=0.35, =0.05 (one-sided) and power of 80%. Using these operating characteristics, the study plan is as follows (Figure 2):

Figure 2 Simon optimal two stage design for SHARED study. At stage 1, nine patients who meet the inclusion criteria will be enrolled. If one or more patients demonstrate pCR, the study will advance to stage 2 to include 25 additional patients.

The sample size was calculated using the Power Analysis and Sample Size software program (PASS 16, NCSS Kaysville Utah USA).

EFS, DFS and OS will be analysed with the KaplanMeier method and the stratified Log rank test. The hazard ratio and its 95% confidence interval will be estimated with the Cox proportional hazards model. The incidences of the AEs and surgical AEs will be analysed using Fishers exact test. All comparisons are one-sided at the 0.05 level of significance. Data will be analysed with SAS version 9.4 statistical software (SAS Institute Inc., Cary, NC, USA).

A number of clinical studies in patients with locally advanced G/GEJ cancers have evaluated the feasibility and efficacy of multimodal treatment approaches that center on a tumor-removing surgery with preoperative or postoperative chemotherapy or radiotherapy.9,2731 Encouraged by the promising results from CHECKMATE-57720 the focus has been shifted towards the regimens that combine checkpoint inhibitors with chemotherapy in adjuvant or neoadjuvant settings (eg, ATTRACTION-5, KEYNOTE-585, MATTERHORN, and NCT04139135) for advanced G/GEJ cancers. The SHARED study is designed to begin with induction chemotherapy with anti-PD-1 to achieve maximum synergistic effects with subsequent cCRT. Given the potential of radiotherapy to revert the immune-suppressive tumor microenvironment, the addition of anti-PD-1 to cCRT is expected to provide a holistic solution for patients at a clinical-stage of T3N2-3M0, T4aN+ M0 or T4bNanyM0, a heterogenous population of both operable and inoperable patients.

Overall, there is a strong rationale warranting a phase 2 clinical trial to explore sintilimab combined with concurrent chemoradiotherapy in locally advanced G/GEJ cancers. The study aims are twofold, targeting to increase the pCR rate for operable patients to prolong the overall survival while ensuring that all patients, including inoperable patients, will gain more survival benefits from surgery. In addition, this study also has the capacity to prospectively evaluate the prognostic value of the status of TMB and MSI, PD-L1 expression level and tumor biomarkers, which can be applied to define eligibility criteria and stratification factors for further trials in locally advanced G/GEJ cancers.

The trial is ongoing, and no data is available.

The trial has been approved by the Ethics Committee of the Comprehensive Cancer Centre of Drum Tower Hospital. All patients are required to sign the written informed consent.

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

All investigators will not receive any remuneration. This research did not receive any grant from funding agencies in the public, commercial or not-for-profit sectors.

Innovent Biologics, Inc. provided the sintilimab, but had no role in study design, or writing of the protocol. The authors report no other conflicts of interest in this work.

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12. Kang Y-K, Boku N, Satoh T, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390(10111):24612471. doi:10.1016/S0140-6736(17)31827-5

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Efficacy and Safety of Sintilimab in Combination with Concurrent Chemo | CMAR - Dove Medical Press

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CRISPR Therapeutics Eyes Historic First in Gene Therapy – BioSpace

Posted: June 22, 2022 at 2:40 am

CRISPR Therapeutics(CRISPR) could be on the cusp of achieving a first in gene therapy, the first company to achieve regulatory approval for a CRISPR-Cas9 program. The company is anticipating the filing of a Biologics License Application for CTX001, a potential cure for transfusion-dependent beta-thalassemia (TDT) and severe sickle cell disease (SCD).

On Tuesday, the Cambridge, MA-based gene editing company hosted an Innovation Day presentation that highlighted its pipeline and the promise that its multiple approaches have in mitigating or even curing different diseases. Chief Executive Officer Samarth Kulkarni said it has been less than 10 years since Jennifer Doudna and Emmanuelle Charpentier first published an article in the journal Science about gene editing technology and less than eight years since CRISPR Therapeutics was founded on that technological promise. Now, the company is on the cusp of vying for potential approval of its CRISPR therapy, he said.

CTX001, also known as exa-cel, is a CRISPR-Cas9-based gene editing therapy for both TDT and SCD. Earlier this month, CRISPR and its partner Vertex Pharmaceuticals released positive data for exa-cel in TDT and SCD. In the first space, data showed that 42 of 44 patients with TDT who received exa-cel remained transfusion free for up to 37.2 months. The two patients who were not transfusion free had 75% and 89% reductions in transfusion volume, respectively, the companies said. In SCD, all 31 patients with disease characterized by recurrent vaso-occlusive crises (VOCs) were free of the issues following treatment with the gene therapy. Data showed the patients had a duration of up to 32.3 months, CRISPR and Vertex reported. The two companiesexpanded their partnership in this space last year.

We are extremely excited about exa-cel, Kulkarni said.

Phuong Khanh (P.K.) Morrow, CRISPRs new chief medical officer, echoed Kulkarni, saying that she believes exa-cel will be the first CRISPR-Cas9 product approved for both TDT and sickle cell disease. Her prediction comes about a week after an advisory committee with the U.S. Food and Drug Administration recommended approval of a different gene therapy approach for these diseases that were developed by bluebird bio.

In immuno-oncology, CRISPR is also blazing a trail with its approach, particularly with CTX130, a donor-derived gene-edited allogeneic CAR T therapy that targets CD70, which is expressed on various solid tumors and hematologic malignancies. The company is developing the asset for solid tumors, such as renal cell carcinoma, as well as T cell and B cell hematologic cancers. Morrow suggested the positive data the company has seen with CRX130 in both solid and hematologic tumors is something of the Holy Grail that researchers have been searching for."

In May, CRISPR presented exciting CTX130 data from two Phase I studies for relapsed or refractory renal cell carcinoma and various subtypes of lymphoma. The company reported positive early signs, including an overall response rate of 71% from patients with T-cell lymphoma. Of those, 29% experienced a complete response, CRISPR said.

In renal cell carcinoma, cancer that expresses high levels of CD70, CTX130 is also showing significant promise, even leading to a complete response in one patient. Renal cell carcinoma represents a high unmet need, with less than 20% of patients surviving beyond five years. About 40% of RCC patients have shown poor response rates to current therapies.

There is a high potential opportunity with CTX130 because of the CD70 expression in RCC, Morrow said.

Beyond those two assets, CRISPR is also advancing other therapeutics. The company is also developing VCTX210, a potential treatment for type 1 diabetes that is being co-developed with ViaCyte. VCTX210 is an allogeneic, gene-edited, stem cell-derived therapy designed to generate pancreatic cells that can evade recognition by the immune system, which would otherwise destroy them. Earlier this year, the companies dosed the first patient in a Phase I study. As BioSpace previously reported, the goal is for the cell line to be differentiated into pancreatic endoderm cells, generatingglucose-responsive insulin-secreting cells in the patient. It is expected that about 10 patients will be included in the study. Data is anticipated by the end of the year.

While those programs for CRISPR Therapeutics stand out, Kulkarni said the company sees significant potential with its total pipeline, with a chance to delve into multiple disease indications and potentially bring new treatment options to patients.

Were very excited about the potential, he said.

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New collaboration to accelerate advancements in gene therapies for dementia – BioPharma-Reporter.com

Posted: June 22, 2022 at 2:40 am

Through the partnership, the CGT Catapult will work with UK academic centers of excellence and the UK DRI to identify new AAV-based gene therapies with high potential to become new medicines for dementia. The organizations will then create detailed development plans for each project and potentially conduct early research activities in order to prepare assets for further investment.

With a team of more than 400 cell and gene therapy experts and headquarters at St Guys hospital in London, the CGT Catapult is an organization dedicated to the advancement of cell and gene therapies.

Meanwhile, the national UK Dementia Research Institute (UK DRI) is the single biggest investment in dementia research in the UK with more than 750 researchers. It was established in 2017 by the Medical Research Council, Alzheimers Society and Alzheimers Research UK and is hosted across six top UK universities: University of Cambridge, Cardiff University, University of Edinburgh, Imperial College London and Kings College London, with its central hub at University College London.

The UK DRIs partnership with the CGT Catapult aims to leverage the expertise and resource of both organizations to accelerate the translation of novel gene therapy approaches to the clinic.

Matthew Durdy, CEO of CGT Catapult, said: Dementia is increasing, under-researched and has very limited treatment options. Cell and gene therapies have in the past shown to be highly effective in treatment areas where other therapies have had limited success. It is therefore vital that we fully explore how cell and gene therapies could be used to address this unmet medical need, and we look forward to working closely with the UK DRI to identify and accelerate the most promising therapies.

Dementia has been one of the leading causes of mortality in the UK since 2015.Over 850,000 people in the UK have dementia and the number of people with dementia will continue to grow as the population ages.

While new and improved treatments for heart disease and cancer are reducing mortality, a lack of effective treatment options for neurodegenerative conditions means that dementia-related deaths continue to rise.

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UNE researcher awarded $1.8 million to study chronic pain relief through gene therapy – University of New England

Posted: June 22, 2022 at 2:39 am

Chronic pain affects millions of people worldwide, yet popular treatments for pain including surgery and opioid medications can have disastrous side effects of their own. But with $1.8 million in funding from the National Institute of Neurological Disorders and Stroke (NINDS), a University of New England researcher will explore non-opioid treatments for chronic pain at the cellular level.

Benjamin Harrison, B.Sc., Ph.D., assistant professor of biochemistry and nutrition, will use the five-year R01 grant from the National Institutes of Health to study how to reduce the excitability of nociceptors, which are neurons that transmit pain signals in response to painful injuries.

Harrison and his team have discovered that nociceptors contain a protein called "CELF4, an RNA binding protein they theorize inhibits the production of pro-nociceptive, or pro-pain-sensing, cellular components. Harrisons research will focus on delivering CELF4 into pain neurons, where this protein will limit the synthesis of ion-channels, receptors, and other molecules that sensitize them.

Specifically, the researchers will study if a locally administered adeno-associated virus can stimulate production of CELF4 and reduce pain in those areas an approach known as gene vector therapy.

Harrison remarked that the innovative approach could prove beneficial for those living with chronic pain but who do not want to undergo surgeries which can be expensive and leave people with no sensation at all or use powerful pain-reducing medications like addictive opioids.

There are some chronic pain conditions that are simply intolerable, and people with those conditions are willing to do severe surgeries to reduce their pain, Harrison remarked. Using this novel gene therapy vector approach, we can develop pain therapies that are less invasive than surgery and carry fewer risks than conventional opioid medications.

Future directions for the research could include partnerships with clinicians for clinical trials, Harrison said.

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Global Gene Therapy Market Research Report 2022-2031 Featuring Major Players – Novartis AG; Bluebird bio, Inc.; Spark Therapeutics, Inc; Audentes…

Posted: June 22, 2022 at 2:39 am

DUBLIN, June 20, 2022 /PRNewswire/ -- The "Gene Therapy Global Market Report 2022: By Gene, By Vector, By Application, By End-User" report has been added to ResearchAndMarkets.com's offering.

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The global gene therapy market is expected to grow from $5.77 billion in 2021 to $7.37 billion in 2022 at a compound annual growth rate (CAGR) of 27.8%.

The growth is mainly due to the companies resuming their operations and adapting to the new normal while recovering from the COVID-19 impact, which had earlier led to restrictive containment measures involving social distancing, remote working, and the closure of commercial activities that resulted in operational challenges.

The market is expected to reach $21.25 billion in 2026 at a CAGR of 30.3%

The gene therapy market consists of sales of gene therapy related services by entities (organizations, sole traders and partnerships) that manufacture gene therapy drugs. Gene therapy is used to replace faulty genes or add new genes to cure disease or improve the body's ability to fight disease. Only goods and services traded between entities or sold to end consumers are included.

The main types of gene therapy are antigen, cytokine, suicide gene and others. Antigen is a poison or other foreign substance that triggers an immunological response in the body, including antibody formation. The different vectors include viral vector, non-viral vector, others and is used in oncological disorders, rare diseases, cardiovascular diseases, neurological disorders, infectious diseases, others. it is implemented in various sectors such as hospitals, homecare, specialty clinics, others.

Incidences of cancer and other target diseases have been increasing significantly, which is calling for effective treatments, driving the growth of the gene therapy market. The rise in the number of cancer cases across the globe is likely to contribute to the growth of the gene therapy market during the forecast period. According to the American Cancer Society, there were 1.7 million new cases and 0.6 million cancer deaths in 2019 in the USA.

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The four most common types of cancer worldwide are lung, prostate, bowel, and female breast cancer, accounting for 43% of all the new cancer cases. Therefore, the rise in the cancer incidence rate globally is anticipated to boost the demand for the gene therapy market over the forthcoming years. Gene therapy is one of the most effective treatments in oncology.

In this treatment, new genes are introduced into a cancerous cell or the surrounding tissue to cause cell death or slow the growth of cancer. For instance, in September 2019, RMIT University, Australia has found that non-viral gene therapy can be used to speed up cancer research, which can bring patient-friendly cancer treatment in the market.

The high prices of gene therapy medicines are expected to limit the growth of the gene therapy market. The pressure to contain costs and demonstrate value is widespread. Political uncertainty and persistent economic stress in numerous countries are calling into question the sustainability of public health care funding. In less wealthy countries, the lack of cost-effective therapies for cancer and other diseases has influenced the health conditions of the population and has led to a low average life expectancy.

Luxturna, a one-time treatment for acquired retinal eye disease, costs $850,000 in the US and 613,410 in the UK, despite a markdown that is applied through Britain's National Health Service. Zolgensma, for spinal muscular atrophy, is valued at $2.1 million in the US and Zynteglo, which focuses on a rare genetic blood disorder, costs $1.78 million, thus restraining the growth of the market.

The use of machine learning and artificial intelligence is gradually gaining popularity in the gene therapy market. Artificial intelligence (AI) is the simulation of human intelligence in machines, which are programmed to display their natural intelligence. Machine learning is a part of AI.

Machine learning and AI help companies in the gene therapy market to conduct a detailed analysis of all relevant data, provide insights between tumor and immune cell interactions, and offer a more accurate evaluation of tissue samples often conflicted between different evaluators. It is also expected to reduce turnaround time and also the cost of gene therapies.

Major players in the gene therapy market are

Novartis AG

Bluebird Bio, inc.

Spark Therapeutics, inc.

Audentes Therapeutics

Voyager Therapeutics

Applied Genetic Technologies Corporation

UniQure N.V.

Celgene Corporation

Cellectis S.A.

Sangamo Therapeutics

Gilead Lifesciences, inc.

Orchard Therapeutics

Sibiono GeneTech Co., Ltd.

Gensight Biologics S.A.

Shanghai Sunway Biotech Co., Ltd.

Biogen

Sarepta Therapeutics, inc.

Sangamo Therapeutics

Audentes Therapeutics

Regenxbio, inc.

Gegenxbio, inc.

Oxford BioMedica plc.

Dimension Therapeutics, inc.

Bristol-Myers Suibb Company

Sanofi

Taxus Cardium Pharmaceuticals Group, inc. (Gene Biotherapeutics)

Shrine plc.

Benitech Biopharma

Transgene

Epeius Biotechnologies Corp.

Calimmune, inc.

Key Topics Covered:

1. Executive Summary

2. Gene Therapy Market Characteristics

3. Gene Therapy Market Trends And Strategies

4. Impact Of COVID-19 On Gene Therapy

5. Gene Therapy Market Size And Growth5.1. Global Gene Therapy Historic Market, 2016-2021, $ Billion 5.1.1. Drivers Of The Market 5.1.2. Restraints On The Market 5.2. Global Gene Therapy Forecast Market, 2021-2026F, 2031F, $ Billion 5.2.1. Drivers Of The Market 5.2.2. Restraints On the Market

6. Gene Therapy Market Segmentation6.1. Global Gene Therapy Market, Segmentation By Gene Type, Historic and Forecast, 2016-2021, 2021-2026F, 2031F, $ Billion

Antigen

Cytokine

Suicide Gene

Others

6.2. Global Gene Therapy Market, Segmentation By Vector, Historic and Forecast, 2016-2021, 2021-2026F, 2031F, $ Billion

Viral Vector

Non-Viral Vector

Others

6.3. Global Gene Therapy Market, Segmentation By Application, Historic and Forecast, 2016-2021, 2021-2026F, 2031F, $ Billion

Oncological Disorders

Rare Diseases

Cardiovascular Diseases

Neurological Disorders

Infectious Diseases

Others

6.4. Global Gene Therapy Market, Segmentation By End Users, Historic and Forecast, 2016-2021, 2021-2026F, 2031F, $ Billion

Hospitals

Homecare

Specialty Clinics

7. Gene Therapy Market Regional And Country Analysis7.1. Global Gene Therapy Market, Split By Region, Historic and Forecast, 2016-2021, 2021-2026F, 2031F, $ Billion 7.2. Global Gene Therapy Market, Split By Country, Historic and Forecast, 2016-2021, 2021-2026F, 2031F, $ Billion

For more information about this report visit https://www.researchandmarkets.com/r/wzvr47

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Research and MarketsLaura Wood, Senior Managerpress@researchandmarkets.com

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Here’s one way gene therapy could change the future of mountain climbing – Out There Colorado

Posted: June 22, 2022 at 2:39 am

Whether it's due to jetpacks, augmented reality, or gene therapy, the future of mountaineering might look very different. In terms of gene therapy, this technology may have the potential to make the mountains more accessible and much safer.

Through years ofresearch into a sometimes fatal condition commonly known as 'altitude sickness,' scientists have determined that symptoms of the condition, also called chronic mountain sickness (CMS), are most likely the result of a population-specific "maladaptation" that impactsup to half of the human population. In other words, some groups of people are genetically inclined to experience severe altitude sickness symptoms because their genes limit their ability to to adjust to high elevation environments. The basis for this assumption lies in how some populations that have traditionally lived at higher elevations around the globe, like those in the Himalayas, tend to be less susceptible to the condition.

If altitude sickness is indeed the result of genetics developed over time, this may mean that the condition could be treated with gene therapy. Research has already found several "candidate genes" that could be the underlying cause behind the maladaptation, meaning that if these genes were successfully targeted with treatment, it may help to limit effects of the condition.

As might be expected, gene therapy is very complicated. Cleveland Clinicdescribes the process as a doctor delivering a healthy copy of a gene to cells inside the body via injection or IV with the hope that the healthy gene will "replace a damaged (mutated) gene, inactivate a mutated gene, or introduce an entirely new gene." Obviously, a ton of research and development must also go into creating that healthy gene first, but this could mean that if scientists are able to fully determine what aspect of the genetic code is causing altitude sickness, they may be able to alter it in a way that eliminates the maladaptation.

If gene therapy technology as it relates to altitude sickness continues to develop, it may add another tool that some people could use to better their mountain climbing potential. Having another option for combating altitude sickness would be hugely beneficial, as only a couple medicines are available for preventing altitude sickness (dexamethasone and acetazolamide,2021) and only one medicine is recommended as a truly effective treatment (dexamethasone).

Not only would a gene therapy option make exploring the mountains safer for many of those already doing so, it would also make high-elevation landscapes more accessible for those that may avoid them due to CMS concerns. While many people don't start to feel the effects of elevation until they've spent several hours above 8,000 feet, others can experience symptoms of a devastating degree at a much lower elevation in a much shorter time frame during a layover at Denver International Airport, for example. For those that face altitude sickness concerns on a regular basis, this technology could be life-changing, and for the rest of us, it could make the mountains a lot more fun.

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Europe Cell and Gene Therapy Market is Poised to Grow at a CAGR of 23% during the Forecast Period of 2022-2031 – Digital Journal

Posted: June 22, 2022 at 2:39 am

The Europe cell and gene therapy market by revenue is expected to grow at a CAGR of over 23% during the period 20222031.

The global cell and gene therapy market is observing significant mergers and acquisition activities, product sales, and new market authorizations. In 2026, the market is expected to grow almost four times more than the current value, with new product approvals expected annually. Although initial product approvals have been for relatively small patient groups, the significant pipeline of cell & gene therapy studies for diseases such as hemophilia and various forms of blindness will significantly expand. In addition, the Europe market is witnessing steady growth due to the increased availability of funds from several public and private institutes. There is increased support from regulatory bodies for product approvals and fast-track product designations, which encourage vendors to manufacture products at a fast rate. Moreover, with over 237 regenerative medicines companies headquartered in Europe, the region is seen as the favorite destination for cell and gene therapy manufacturing.

The following factors are likely to contribute to the growth of the Europe cell and gene therapy market during the forecast period:

CMOs Offering Vector Manufacturing Services for Cell and Gene Therapy Companies Robust Cell & Gene Therapies in the Pipeline Increase in Strategic Acquisitions Regulatory Support for Cell and Gene Therapy Products

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The study considers the present scenario of the Europe cell and gene therapy market and its market dynamics for the period 20222031. It covers a detailed overview of several market growth enablers, restraints, and trends. The report offers both the demand and supply aspects of the market. It profiles and examines leading companies and other prominent ones operating in the market.

Europe Cell and Gene Therapy Market Segmentation

The Europe cell and gene therapy market research report includes a detailed segmentation by product, end-user, application, geography. A high potential to treat several chronic diseases, which cannot be effectively treated/cured through conventional methods otherwise, is propelling the growth of gene therapies. Gene therapies are regarded as a potential revolution in the health sciences and pharmaceutical fields. The number of clinical trials investigating gene therapies is increasing in Europe, despite the limited number of products that have successfully reached the market. However, gene therapies show slow progress and promising prospect in terms of treatments. High support from regulatory bodies to commercialize these products and make them affordable to patients is another important factor contributing the market growth.

Delivering cell and gene therapies requires specialized facilities, capabilities, and clinician skills. Therefore, manufacturers are working in tandem with chosen treatment centers (hospitals) to establish the protocols and procedures necessary to receive the product and therapies. While cell therapies represent a paradigm shift in the treatment of several incurable, chronic diseases, with durable responses and long-term disease control measures, hospitals appear an ideal location to carry out these procedures. Hospitals are growing at a significant rate due to the increasing target population in Europe. Tier-I hospitals are proving to be sought-after network partners for cell and gene therapy developers. They tend to be in major population centers, have adequate financial and personnel resources, and value the prestige that comes with being the first movers in an innovative treatment area.

Oncology accounted for a share of over 30% in 2020. While cancer treatments have evolved and undergone massive developments in recent years, it continues to be one of the deadliest diseases confronted by humans. Traditional cancer therapies have a curative effect in the short term; however, they have side effects, thereby decreasing the patients quality of life. Cell and gene therapies for certain types of cancers have been promising results. The chimeric antigen receptor- (CAR-) T cell therapy is one of the most recent innovative immunotherapies and is rapidly evolving. CAR-T cell therapies are developing rapidly, and many clinical trials have been established on a global scale, which has high commercial potential for the treatment of cancer. Immunotherapies based on CAR-T cells go one step further, engineering the T cells themselves to enhance the natural immune response against a specific tumor antigen. CAR-T clinical trials have shown high remission rates, up to 94%, in severe forms of blood cancer, thereby increasing the market growth.

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INSIGHTS BY GEOGRAPHY

Germany, France, the UK, Italy, and Spain play a significant role in the Europe cell and gene therapy market. Clinical trials and the number of manufacturing facilities are increasing slowly in the European region. The region has become a major R&D destination for several vendors as the funding for cell & gene therapies is increasing. Europe has supported collaborative efforts in gene transfer and gene therapy research. In addition, the target patient population is increasing across Europe; there were an estimated 3.9 million new cases of cancer and 1.9 million cancer deaths in Europe in 2018. In addition, the prevalence surveys in the UK and Denmark indicate that there are 34 people with one or more wounds per 1,000 people. Favorable government support in terms of product approvals, reimbursement and coverage, and high R&D funding to academic institutes that are involved in the development of cell and gene therapies are expected to boosting the market in Europe.

INSIGHTS BY VENDORS

Novartis, Spark Therapeutics, Amgen, Gilead Sciences, and Organogenesis are the leading players in the Europe cell and gene therapy market. The market offers tremendous growth opportunities for existing and future/emerging players on account of the presence of a large pool of target patient population with chronic diseases such as cancer, wound disorders, diabetic foot ulcer, CVDs, and other genetic disorders. Recent approvals have prompted an unprecedented expansion among vendors. While a few vendors are opting for in-house production of cell and gene therapies, a substantial number of vendors are preferring third-party service providers, including CMOs.

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Europe Cell and Gene Therapy Market is Poised to Grow at a CAGR of 23% during the Forecast Period of 2022-2031 - Digital Journal

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BlueAllele Corporation continues to advance therapeutic approaches using novel gene correction technologies and secures third patent from the USPTO -…

Posted: June 22, 2022 at 2:39 am

OAKDALE, Minn., June 21, 2022 /PRNewswire/ -- BlueAllele Corporation, a biotechnology company focused on advancing transformational gene correction technologies, announced today that the United States Patent and Trademark Office (USPTO) has issued U.S. Patent No. 11,365,407 (the '407 Patent) related to its proprietary in vivo gene correction methodologies.

BlueAllele was founded with the ambitious objective to develop methodologies for single-dose treatments to cure the most debilitating and devastating genetic diseases. Over 5,000 genetic diseases, which are caused by mutations within a gene, have been identified and diagnosed in humans. The mutations can inactivate gene function, referred to as loss-of-function mutations, or create an undesirable function, referred to as gain-of-function mutations. BlueAllele has developed transformational gene correction technologies utilizing its proprietary PALIDON repair template platforms to achieve gene correction that is precise, durable, and capable of treating a broad range of both loss-of-function and gain-of-function mutations.

Dr. Nicholas Baltes, BlueAllele's chief scientific officer, said, "We saw that there was a large gap in the capabilities of the genetic tools for gene correction and the development of effective, safe and lifelong therapies. We set out to close the gap."

Unlike traditional gene therapy where the corrective sequences remain extrachromosomal, PALIDON is integrated into the cell's DNA thereby providing potential lifelong therapeutic effects. Further, unlike gene knockout approaches where gene function is destroyed, PALIDON provides replacement sequence for restoration of gene function.

The distinctive palindromic design of BlueAllele's PALIDON repair templates has unlocked the full potential of the cell's highly active NHEJ pathway. In doing so, PALIDON can increase the efficacy of gene correction events, improve safety and be used for the therapeutic treatment of a wide range of diseases. BlueAllele has expanded upon this foundational feature with the design of additional repair template platforms for treating specific classes of genetic diseases. PALIDON+ was designed for autosomal dominant diseases and functions to remove unwanted gene products while simultaneously restoring normal protein function. PALIDON DT was designed to address repeat expansion diseases and functions to prevent transcription through the expansion.

"We are excited about the potential of our PALIDON platforms for gene correction in patients," said Joseph B. Saluri, BlueAllele's chief executive officer. "What was once considered beyond reach is now closer to becoming a reality."

About BlueAllele's Patents

The newly granted '407 Patent includes claims covering adeno-associated viral vectorsharboring BlueAllele's proprietary PALIDON transgene design. The claims also cover adeno-associated viral vectors harboring a PALIDON transgene containingFactor 9 coding sequences for treating patients with hemophilia B.

U.S. Patent 11,254,930 (the '930 Patent) includes claims covering recombinant nucleic acids containing BlueAllele's novel PALIDON transgene structure, which includes splice acceptors, coding sequences and terminators for correcting gene function. The PALIDON transgenes can be used with any nuclease, any delivery system and any application for treating a genetic disease in any tissue or cell.

U.S. patent 11,091,756 (the '756 Patent) includes claims covering methods for using PALIDON to edit genes in any cell type and system, in vitro or in vivo applications, as well as its use for correcting any gene in the genome.

The '407, '930 and '756 Patents are exclusively owned by BlueAllele Corporation and provide broad coverage for the development and advancement of human gene correction technologies.

BlueAllele Corporation is a biotechnology company committed to advancing transformational gene correction technologies, including its patented PALIDON PALIDON+ and PALIDON DT repair template platforms. BlueAllele is a member of Medical Alley, The Global Epicenter of Health Innovation and Care. For more information, visit http://www.blueallele.com.

BlueAllele is seeking strategic collaborators for leading innovation for gene correction technologies. If interested, please contact us via http://www.blueallele.com/contact.

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Global Gene Therapy for Ovarian Cancer Market Prescriptive Research, Production Information 2022-2029 |Takara Bio, VBL Therapeutics, CELSION, Targovax…

Posted: June 22, 2022 at 2:39 am

The recently released report on the global Gene Therapy for Ovarian Cancer Market 2022 to 2029 provides a comprehensive evaluation of the respective industry that contains several aspects of product specifications, Gene Therapy for Ovarian Cancer industry segmentation supported by numerous characteristics, and an analysis of the competitors landscape. The new research document assesses the desired prospects and existing industry position, offering powerful insights and crucial updates on the corresponding segments included in the global Gene Therapy for Ovarian Cancer market for the projected period from 2022 to 2029.

The report offers detailed insights into the Gene Therapy for Ovarian Cancer market which covers the regional inspection of the industrial data and its estimation analysis along with a deep summary and description related to the Gene Therapy for Ovarian Cancer market across the globe. The given study is a prominent attempt by industry specialists and experts to project and evaluate the Gene Therapy for Ovarian Cancer industry.

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Besides this, the researchers have notified that the global Gene Therapy for Ovarian Cancer market report offers a fundamental synopsis of the Gene Therapy for Ovarian Cancer industry along with prime applications, profit margin, and industry chain structure. An in-depth analysis of the Gene Therapy for Ovarian Cancer market is delivered for the international industries such as newer development trends, competitive landscape analysis, and notable regions development status. Different development policies and plans, manufacturing procedures, as well as cost structures, are properly discussed in the global Gene Therapy for Ovarian Cancer market.

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Significant Players involved in the Gene Therapy for Ovarian Cancer market report:

Takara BioVBL TherapeuticsCELSIONTargovax

Gene Therapy for Ovarian Cancer Market splits into Product Types:

IntravenousIntratumoralIntraperitoneal

Key Applications of the Gene Therapy for Ovarian Cancer market are:

Ovarian Cancer (unspecified)Recurrent Ovarian Epithelial CancerPlatinum-Resistant Ovarian Cancer

The Geographical assessment of the Gene Therapy for Ovarian Cancer market is:

North America Market(United States, Canada, North American country and Mexico),Europe Market (Germany, Gene Therapy for Ovarian Cancer France, UK, Russia and Italy),Asia-Pacific Market (China, Gene Therapy for Ovarian Cancer Japan and Korea, Asian nation, India and Southeast Asia),South America Market (Brazil, Argentina, Republic of Colombia etc.),Middle East & Africa Market (Saudi Arabian Peninsula, UAE, Egypt, Nigeria and South Africa)

The new study report gives a systematic and descriptive approach to the global Gene Therapy for Ovarian Cancer market. It constructs industry dynamics, the overall extent of growth in distinct segments, regions as well as various other parameters that have been immensely effective in enlarging the industry size and value. Therefore, this document aimed at delivering a clear perspective of all possible conditions and structures in the global Gene Therapy for Ovarian Cancer market.

Read Complete Analysis Report for Better Understanding (Description, TOC, List of Tables & Figures and Many More): https://marketresearchexpertz.com/report/global-gene-therapy-ovarian-cancer-market-461384

Vital Questions Answered in the Gene Therapy for Ovarian Cancer market report:

What is the projected growth rate, share, and size of the Gene Therapy for Ovarian Cancer market? What are the available driving forces in the Gene Therapy for Ovarian Cancer market for the estimated period from 2022 to 2030? What was the value of the Gene Therapy for Ovarian Cancer market in Europe, North America & Asia Pacific? What is the forecasted industry analysis of the global Gene Therapy for Ovarian Cancer market? Who are the prominent industry players of the Gene Therapy for Ovarian Cancer market globally? How industry players have grabbed a competitive edge over other competitors? At what CAGR is the Gene Therapy for Ovarian Cancer market expected to expand? What are the crucial challenges and threats limiting the progress of the Gene Therapy for Ovarian Cancer industry? What are the topmost trends in the Gene Therapy for Ovarian Cancer market?

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Global Gene Therapy for Ovarian Cancer Market Prescriptive Research, Production Information 2022-2029 |Takara Bio, VBL Therapeutics, CELSION, Targovax...

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New Data Presented at Cure SMA Reveal Residual Unmet Needs in Young SMA Patients Treated With Gene Therapy and Suggest Further Potential of Using…

Posted: June 22, 2022 at 2:39 am

CAMBRIDGE, Mass., June 15, 2022 (GLOBE NEWSWIRE) -- BiogenInc.(Nasdaq: BIIB) will present new data from clinical studies aimed at assessing remaining unmet needs for people living with spinal muscular atrophy (SMA) and evaluating the potential impact of SPINRAZA (nusinersen) in different patient populations at the SMA Research & Clinical Care Meeting hosted by Cure SMA this week in Anaheim, Calif. Biogen is a presenting sponsor of Cure SMAs 2022 Annual SMA Conference, the worlds largest meeting dedicated to SMA research and care.

The data we are presenting at this years Cure SMA conference including the latest updates from the RESPOND and DEVOTE studies reinforce Biogens commitment to evaluating the potential of SPINRAZA to further improve clinical outcomes for individuals with SMA, said Maha Radhakrishnan, M.D., Chief Medical Officer at Biogen. There are key unmet needs within the SMA community and we are committed to addressing these through our ongoing research that includes active enrollment in three global clinical studies.

SMA Research Updates Growing enrollment in the RESPOND study indicate there are residual unmet clinical needs in infants and toddlers with SMA following treatment with Zolgensma (onasemnogene abeparvovec). The Phase 4 study is evaluating the clinical benefit and safety of SPINRAZA in infants and toddlers with SMA who have unmet needs following treatment with the gene therapy.

Since initial findings from nine patients were shared in March 2022, baseline and safety data from 16 patients enrolled in RESPOND (as of November 2021) are being presented. All enrolled study participants reported suboptimal clinical status across a variety of measures at baseline, with 13 of 16 showing this in multiple areas, including motor and respiratory functions and swallowing/feeding ability. After beginning SPINRAZA treatment, initial safety findings (median duration of 132.5 days) show three participants experienced a serious adverse event (AE) during the study period; none of these events were considered related to SPINRAZA treatment. The RESPOND study (NCT04488133) is currently enrolling participants at 20 sites worldwide; more information about the eligibility criteria is available at clinicaltrials.gov.

Biogen will also share final data from Part A of the ongoing, three-part DEVOTE study evaluating the safety and tolerability of investigational, higher doses of nusinersen.* Results from Part A, an open-label safety evaluation period in children and teens with later-onset SMA, suggest that a higher dosing regimen (28 mg) of nusinersen leads to higher levels of the drug in the cerebrospinal fluid and is generally well-tolerated, with most AEs reported considered to be mild in severity. The most common AEs reported were headache and procedural pain. Two serious AEs (fall, femur fracture) were reported in one participant during the study period. No AEs were considered related to nusinersen and some were related to treatment administration. The totality of Part A data supports further development of a higher dose ofnusinersen.

Currently, Part B and Part C of DEVOTE evaluating an investigational, higher dose of nusinersen are enrolling at 52 sites worldwide. Information on the DEVOTE trial (NCT04089566) is available at clinicaltrials.gov.

Featured SPINRAZA Data Presentations Include:

*Nusinersen is currently commercialized under the brand name SPINRAZA and the U.S. Food and Drug Administration-approved dose is 12 mg. As a foundation of care in SMA, more than 13,000 individuals have been treated with SPINRAZA worldwide.1

About SPINRAZA(nusinersen)The SPINRAZA clinical development program encompasses 10 clinical studies, which have included more than 300 individuals across a broad spectrum of patient populations,2including two randomized controlled studies (ENDEAR and CHERISH). The ongoing SHINE and NURTURE open-label extension studies are evaluating the long-term impact of SPINRAZA. The most common adverse events observed in clinical studies were respiratory infection, fever, constipation, headache, vomiting and back pain. Laboratory tests can monitor for renal toxicity and coagulation abnormalities, including acute severe low platelet counts, which have been observed after administration of some ASOs.

Biogen licensed the global rights to develop, manufacture and commercialize SPINRAZA from Ionis Pharmaceuticals, Inc. (Nasdaq: IONS), the leader in antisense therapeutics. Please click here forImportant Safety Informationandfull Prescribing Informationfor SPINRAZA in the U.S., or visit your respective countrys product website.

About Spinal Muscular Atrophy (SMA)SMA is a rare, genetic, neuromuscular disease that affects individuals of all ages. It is characterized by a loss of motor neurons in the spinal cord and lower brain stem, resulting in progressive muscle atrophy and weakness.3SMA is caused by a deficiency in the production of survival motor neuron (SMN) protein due to a damaged or missingSMN1gene, with a spectrum of disease severity.3Some individuals with SMA may never sit; some sit but never walk; and some walk but may lose that ability over time.4In the absence of treatment, children with the most severe form of SMA would not be expected to reach their second birthday.3

SMA impacts approximately 1 in 10,000 live births,5-8is a leading cause of genetic death among infants9 and causes a range of disability in teenagers and adults.4

About BiogenAs pioneers in neuroscience, Biogen discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological diseases as well as related therapeutic adjacencies. One of the worlds first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Sir Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today, Biogen has a leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, and developed the first and only approved treatment to address a defining pathology of Alzheimers disease. Biogen is also commercializing biosimilars and focusing on advancing one of the industrys most diversified pipelines in neuroscience that will transform the standard of care for patients in several areas of high unmet need.

In 2020, Biogen launched a bold 20-year, $250 million initiative to address the deeply interrelated issues of climate, health, and equity. Healthy Climate, Healthy Lives aims to eliminate fossil fuels across the companys operations, build collaborations with renowned institutions to advance the science to improve human health outcomes, and support underserved communities.

We routinely post information that may be important to investors on our website atwww.biogen.com.Follow us on social media-Twitter,LinkedIn,Facebook,YouTube.

Biogen Safe HarborThis news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, about the potential benefits, safety and efficacy of nusinersen; the results of certain real-world data; our research and development program for the identification and treatment of SMA; clinical development programs, clinical trials and data readouts and presentations; the potential benefits and results from treatment of SMA; and risks and uncertainties associated with drug development and commercialization. These statements may be identified by words such as aim, anticipate, believe, could, estimate, expect, forecast, goal, intend, may, plan, possible, potential, will, would and other words and terms of similar meaning. You should not place undue reliance on these statements or the scientific data presented.

These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation risks relating to the occurrence of adverse safety events and/or unexpected concerns that may arise from additional data or analysis, including from the DEVOTE, RESPOND and ASCEND studies; the risk that we may not fully enroll our clinical trials, or enrollment will take longer than expected; failure to obtain regulatory approvals in other jurisdictions; risks of unexpected costs or delays; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; regulatory authorities may require additional information or further studies; product liability claims; third party collaboration risks; and the direct and indirect impacts of the ongoing COVID-19 pandemic on our business, results of operations and financial condition. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. Investors should consider this cautionary statement as well as the risk factors identified in our most recent annual or quarterly report and in other reports we have filed with the U.S. Securities and Exchange Commission. These statements are based on our current beliefs and expectations and speak only as of the date of this news release. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

References:

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New Data Presented at Cure SMA Reveal Residual Unmet Needs in Young SMA Patients Treated With Gene Therapy and Suggest Further Potential of Using...

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Monthly Archives: June 2022

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New Data Presented at Cure SMA Reveal Residual Unmet Needs in Young SMA Patients Treated With Gene Therapy and Suggest Further Potential of Using…

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