Vagus Nerve Injuries

– Priority review reduces the BLA review timeline to 6-months and is granted to therapies that, if approved, would provide significant improvements in the treatment, diagnosis or prevention of serious conditions – – If approved, PRGN-2012 would be the first and only available FDA-approved therapy for eligible patients with RRP, a rare and devastating chronic disease for which the current standard-of-care is repeated surgeries – GERMANTOWN, MD, USA I February 25, 2025 I Precigen, Inc. (Nasdaq: PGEN ), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, today announced the US Food and Drug Administration (FDA) has accepted the company’s biologics license application (BLA) for PRGN-2012 (nonproprietary name: zopapogene imadenovec † ), an investigational AdenoVerse ® gene therapy for the treatment of adults with recurrent respiratory papillomatosis (RRP). The FDA granted priority review to the BLA and set a Prescription Drug User Fee Act (PDUFA) target action date of August 27, 2025. The FDA has indicated that they are not currently planning to hold an advisory committee meeting to discuss this application. PRGN-2012 is designed to elicit immune responses directed against cells infected with human papillomavirus (HPV) 6 or HPV 11. PRGN-2012 received Breakthrough Therapy Designation , Orphan Drug Designation , and an accelerated approval pathway from the FDA, and Orphan Drug Designation from the European Commission. If approved, PRGN-2012 would be the first and only FDA-approved therapeutic for the treatment of adults with RRP. RRP is a rare, difficult-to-treat, lifelong neoplastic disease of the upper and lower respiratory tracts caused by infection with HPV 6 or HPV 11 that can be fatal. Currently, there is no cure for RRP and the current standard-of-care is repeated surgeries, which do not address the underlying cause of disease and are associated with significant morbidity. As a result, the cycle of recurrence and surgery continues and patients can require hundreds of lifetime surgeries. 1-7 The cumulative risk of laryngeal injury increases with each RRP surgery, particularly with patients requiring five or more lifetime surgeries. 8 There is high unmet need for a therapeutic alternative to prevent these irreversible surgery-related injuries. The BLA is supported by data from the pivotal Phase 1/2 clinical study ( NCT04724980 ), which were presented at the 2024 American Society of Clinical Oncology (ASCO) annual meeting and published in The Lancet Respiratory Medicine . The pivotal study met its primary safety and efficacy endpoints, with more than 50% of patients achieving Complete Response and more than 85% of patients experiencing a decrease in surgical interventions in the year after PRGN-2012 treatment compared to the year prior to treatment. PRGN-2012 was well-tolerated with no dose-limiting toxicities and no treatment-related adverse events greater than Grade 2. Primary endpoints included safety and Complete Response rate defined as the percentage of patients who require no RRP surgeries in the 12-month period after PRGN-2012 treatment completion. Key secondary endpoints included HPV-specific immune responses, extent of papilloma growth as measured by Derkay scoring, and quality of life as measured by Vocal Handicap Index-10 (VHI-10). “The priority review designation is a testament to the FDA’s recognition of the significant unmet need for the RRP patient population. RRP patients have never had an FDA-approved therapy, relying instead on repeated surgeries to alleviate the symptoms of RRP without addressing the underlying disease,” said Helen Sabzevari, PhD, President and CEO of Precigen. “Treatment with PRGN-2012 has shown significant, durable clinical benefit. We have patients treated with PRGN-2012 who have been surgery-free for more than three years now, bringing hope for an alternative to the cycle of repeated surgeries, which carry immense risk for irreversible damage and significant morbidity. We look forward to working with the FDA over the coming months during their BLA review and hope to introduce the first FDA-approved therapeutic option to the RRP patient population, estimated at more than 27,000 adults in the US, later this year.” AdenoVerse® Precigen’s AdenoVerse platform utilizes a library of proprietary adenovectors for the efficient gene delivery of therapeutic effectors, immunomodulators, and vaccine antigens designed to modulate the immune system. Precigen’s gorilla adenovectors, part of the AdenoVerse library, have potentially superior performance characteristics as compared to current competition. AdenoVerse gene therapies have been shown to generate high-level and durable antigen-specific T-cell immune responses as well as an ability to boost these responses via repeat administration. Superior performance characteristics and high yield manufacturing of AdenoVerse vectors leveraging UltraVector ® technology allows Precigen to engineer cutting-edge investigational gene therapies to treat complex diseases. Precigen: Advancing Medicine with Precision ™ Precigen (Nasdaq: PGEN ) is a dedicated discovery and clinical stage biopharmaceutical company advancing the next generation of gene and cell therapies using precision technology to target the most urgent and intractable diseases in our core therapeutic areas of immuno-oncology, autoimmune disorders, and infectious diseases. Our technologies enable us to find innovative solutions for affordable biotherapeutics in a controlled manner. Precigen operates as an innovation engine progressing a preclinical and clinical pipeline of well-differentiated therapies toward clinical proof-of-concept and commercialization. For more information about Precigen, visit www.precigen.com or follow us on LinkedIn or YouTube . † zopapogene imadenovec is the nonproprietary name for the investigational therapeutic known as PRGN-2012. Zopapogene imadenovec has not been approved by any health authority in any country for any indication. References 1 Mounts, P et al. (1982). “Viral etiology of juvenile- and adult-onset squamous papilloma of the larynx.” Proc Natl Acad Sci U S A 79(17): 5425-5429. 2 Smith, E et al. (1993). “Human papillomavirus infection in papillomas and nondiseased respiratory sites of patients with recurrent respiratory papillomatosis using the polymerase chain reaction.” Arch Otolaryngol Head Neck Surg 119(5): 554-557. 3 Derkay, CS et al. (2008). “Recurrent respiratory papillomatosis: a review.” Laryngoscope 118(7): 1236-1247. 4 Derkay, CS et al. (2019). “Update on Recurrent Respiratory Papillomatosis.” Otolaryngol Clin North Am 52(4): 669-679. 5 Seedat, RY (2020). “Juvenile-Onset Recurrent Respiratory Papillomatosis Diagnosis and Management – A Developing Country Review.” Pediatric Health Med Ther 11: 39-46. 6 Dedo, HH et al. (2001). “CO(2) laser treatment in 244 patients with respiratory papillomas.” Laryngoscope 111(9): 1639-1644. 7 Silver, RD et al. (2003). “Diagnosis and management of pulmonary metastasis from recurrent respiratory papillomatosis.” Otolaryngol Head Neck Surg 129(6): 622-629. 8 So, RJ et al. (2024). “Factors Associated with Iatrogenic Laryngeal Injury in Recurrent Respiratory Papillomatosis.” Otolaryngol Head Neck Surg 170:1091-1098. SOURCE: Precigen

SAN FRANCISCO, Feb. 12, 2024 /PRNewswire/ -- In adolescent athletes who underwent anterior cruciate ligament reconstruction (ACLR), the younger the athlete at the time of primary ACLR and an earlier return to sport (RTS) were significantly associated with an increased rate of secondary ACL injuries, according to new study presented at the 2024 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS). The study, " Predictors of Anterior Cruciate Ligament Reinjury and Return to Sport in Adolescent Athletes," found that when the age of primary ACLR increases by one year, the rate of secondary ACL injury decreases by 29% and a one-month delay in RTS decreases the rate of a secondary ACL injury by 17%. "In our practice, we noticed we are seeing a larger prevalence of ACL injuries in this younger population, but we haven't seen literature that specifically looks at the high school age population," said Bhargavi Maheshwer, MD, lead author and third-year orthopaedic surgery resident at University Hospitals in Cleveland, Ohio. "Many of these athletes were returning for revisions or second opinions after having a retear or a contralateral ACL tear, so it is important to outline the trends behind the risk of having an ACL reinjury. Specifically, the variables that are associated with the higher risk of sustaining these injuries and what can we do from a patient education standpoint to address those variables." ACL injuries in adolescent athletes are increasing mainly due to the rise of younger athletes playing in competitive sports at an earlier age and an increased awareness of ACL injuries.[i],[ii] For younger athletes, an ACL injury can have a major impact. For example, there is significant downtime associated with an ACL tear, which may lead to mental health issues, they are 10 times more likely to develop early arthritis, and there is a 25-35% increased risk of experiencing a secondary ACL tear.[iii] Additionally, up to 14% of adolescents who undergo ACLR do not return to their previous level of play.[iv] The researchers sought to identify recent epidemiologic trends of ACL injuries and recurrent tear rates in high school athletes, and determine variables related to sustaining a secondary ACL injury. Using a prospectively maintained database from a single institution, the team retrospectively reviewed data for all patients under the age of 18 who underwent primary ACLR from 2015-2020. Patients were eligible if they were 13-18 years old, participated in a high school sport, and underwent evaluation and primary ACLR at a single institution. To be included, patients had to have a follow-up duration of six months or more and had not undergone a prior revision ACLR. Outcomes included postoperative complications, re-operations, time to RTS (defined as the number of months following ACLR until the patient was cleared to return to the sport by the operating surgeon), and time to retear or reinjury. Odd ratios were calculated for baseline patient characteristics and the association with the risk of retear. Multivariate Cox regression analysis was performed to identify the relationship between retear and potential risk factors. The results included: A total of 431 adolescent patients were included with a median follow up of over five years – 20.2% (87) sustained a secondary ACL injury and 79.8% (344) did not. Nine percent (39) of patients with a secondary ACL injury experienced a graft failure and 11.2% (48) had a contralateral ACL injury (ACL injury on the uninjured knee). Complication rates were low (n=22 6.1%), with 11 patients experiencing arthrofibrosis (3%), one patient (0.2%) with a superficial wound infection managed with antibiotics and one patient (0.2%) with deep infection that required operative irrigation and debridement. Patients with a secondary ACL injury were older than those who did not have another ACL tear (mean age at surgery 16.2 ± 1.3 years versus 15.6 ± 1.5 years, respectively, p=0.003). After adjusting for all variables, a younger age at primary ACLR and time to RTS were significantly associated with an increased rate of secondary ACL injury. "Nine months is the minimum that we consider it safe to return to sport following ACLR as a rapid return to sport puts you at greater risk of a recurrent injury," said James Everett Voos, MD, FAAOS, orthopaedic surgeon, chairman of orthopaedics at University Hospitals and head team physician for the Cleveland Browns. "For our younger athletes, we should take the time to ensure they are fully recovered and have had a chance to rehabilitate since they are often skeletally immature and still growing. As orthopaedic surgeons, we need to customize the treatment plan for each athlete as not all ACLs are the same, and counsel patients about their type of injury and when to return to the sport based on their rehabilitation and age." # # # 2024 AAOS Annual Meeting Disclosure Statement About the AAOS With more than 39,000 members, the American Academy of Orthopaedic Surgeons is the world's largest medical association of musculoskeletal specialists. The AAOS is the trusted leader in advancing musculoskeletal health. It provides the highest quality, most comprehensive education to help orthopaedic surgeons and allied health professionals at every career level to best treat patients in their daily practices. The AAOS is the source for information on bone and joint conditions, treatments and related musculoskeletal healthcare issues; and it leads the healthcare discussion on advancing quality. Follow the AAOS on Facebook, X, LinkedIn and Instagram. SOURCE American Academy of Orthopaedic Surgeons

Starting a robust exercise program sooner after surgery could prevent patients with dislocated shoulders from sustaining a repeat injury and help them return to sport faster. Researchers spent three years analyzing evidence from 3,600 existing studies and found a tailored exercise program commencing three to six weeks after surgery was the best approach for preventing a secondary shoulder dislocation. Starting a robust exercise program sooner after surgery could prevent patients with dislocated shoulders from sustaining a repeat injury and help them return to sport faster. University of Adelaide researchers spent three years analysing evidence from 3,600 existing studies and found a tailored exercise program commencing three to six weeks after surgery was the best approach for preventing a secondary shoulder dislocation. "Patients who dislocate their shoulder have a high risk of doing it again within six months, and can suffer from recurrent instability," said the University of Adelaide's Dr Timothy Lathlean, an Accredited Exercise Physiologist (AEP) and Post-Doctoral Research Fellow at the Adelaide Medical School and the South Australian Health and Medical Research Institute (SAHMRI). "Our analysis found those who embarked on a robust exercise program after surgery were twice as likely to avoid a recurrent injury than those who used exercise alone to recover from their injury." The researchers found starting a multimodal program -- a combination of exercises targeting strength, coordination, balance and muscular control -- soon after surgery produced better results than standard care programs that rely on strength training only. The review focused on patients who suffered from first time shoulder dislocations that occurred in a forward direction, due to a direct blow to the shoulder. This type of injury often happens while playing sport or in workplace accidents. Shoulder dislocations are particularly common among young males between the ages of 16 and 30 because they are more likely to play contact sports and have physically challenging occupations. "Shoulder dislocation can be disabling and is often accompanied by weakness, stiffness, pain and inability to participate in day-to-day activities and sport," said Dr Lathlean. "People who have experienced this injury can have trouble returning to work or sports and there is an economic burden that comes with that. This could be lessened with more effective treatment and more timely targeted rehabilitation." This research was part of a collaborative project with a PhD researcher at the Texas Tech University Health Sciences Center and the University of Adelaide's School of Allied Health. The findings have been published in the British Journal of Sports Medicine and could help practitioners and researchers alike to get the best results from surgery and rehabilitation. "The results show there is a real need for more sophisticated exercise programs in the rehabilitation phase to improve outcomes for patients and get them back to playing sport sooner," said Dr Lathlean. "Similar approaches are already common practice when recovering from other types of surgery for spine or knee-related injuries and the evidence from this study shows it would be beneficial for acute shoulder injury patients as well."