FAST TRACK USA REGULATORY APPROVAL FOR DRUGS TO TREAT EMERGING INFECTIOUS DISEASES

The Food and Drug Administration has established fast track approval to speed the designation of drugs that efficiently treat serious conditions, in particular those that provide improved advantages over available therapy. Fast track designation was initiated to curtail the time period in the new drug approval procedure and to promote the drug discovery and commercialization of drug products for critical and life-threatening illness and expedite the approval of drug products demonstrating advanced efficacy toward the prevailing one. Single Phase II study is reviewed before approving the drug within fast track designation. This review article highlights the consequences, criteria for fast track designation, fast track designation process, and the timeline for fast track approval.

Abstract 13691: Factors Affecting Extubation Time Post-Cardiac Surgery

Introduction: Early extubation, defined as extubation within 6 hours post-operation, was found to be safe and associated with decreased complications and costs. Recent enhanced recovery after surgery guidelines recommend early extubation for cardiac surgery patients. This retrospective study aimed to assess our institution’s extubation strategy and identify predictive factors of early extubation in our cardiac surgery patients. Methods: Our study included 13,807 adult patients who underwent cardiothoracic surgery from 2010-2019 at our institution. Forward stepwise multivariable logistic regression analysis was used on patients with complete data (n=10,783) to identify predictors of early extubation. Results: Of the 10,783 patients, 3740 (35%) were extubated within 6 hours post-operation. Early extubated patients were younger, had higher BMI and more likely to be fast track designated. These patients more frequently underwent isolated coronary artery bypass graft (CABG), isolated valve or adult congenital surgery than late extubated patients. Early extubated patients had higher incidence of coronary artery disease (CAD) and anxiety, and were less likely to have difficult intubation or require circulatory support post-surgery. Analysis of 10,783 patients showed BMI >30 (OR=1.840, 95% CI=1.624-2.083), fast track designation (OR=1.338, 95% CI=1.12-1.598) and having CAD (OR=1.107, 95% CI=1.007-1.217) to be predictive of early extubation. Data on patient transfer to the ICU were only available from 2014-2018. Within this sub-group of 7296 patients, variables predictive of early extubation included BMI >30 (OR=1.364, 95% CI=1.195-1.557), dayshift transfer to the ICU (OR=1.680, 95% CI=1.516-1.862), fast track designation (OR=1.397, 95% CI=1.115-1.751) and having isolated procedures such as CABG (OR=1.630, 95% CI=1.413-1.880) and valve surgery (OR=1.506, 95% CI=1.300-1.745). Conclusions: BMI >30, having fast track designation, and having CAD are associated with early extubation. When taking into account patient transfer to the ICU, BMI >30, having fast track designation, dayshift transfer to the ICU, and having isolated procedures such as CABG and valve surgery are associated with early extubation.

Brief Report: Rapid Clinical Recovery from Critical COVID-19 with Respiratory Failure in a Lung Transplant Patient Treated with Intravenous Vasoactive Intestinal Peptide

RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) is shown to block replication of the SARS-CoV-2 virus and has been granted Fast Track Designation by the US FDA for the treatment of Critical COVID-19 with Respiratory Failure. We describe the clinical course of the first patient treated with this investigational medication in an open label manner -- a 54 year old patient suffering antibody-mediated rejection of his double lung transplant who contracted COVID-19 with respiratory failure refractory to all currently available therapies. He received three infusions of RLF-100 under an FDA-approved emergency use IND. Within 24 hours of the third infusion, substantial improvement in oxygen saturation and radiographic improvement in characteristic COVID-19 pneumonitis was noted. He was discharged from intensive care at that point and scheduled for discharge to home at 1 week on room air. Despite an intervening hospitalization for trauma, he remains alive and free of respiratory failure at 28 days post treatment.

Brief Report: Rapid Clinical Recovery from Critical COVID-19 with Respiratory Failure in a Lung Transplant Patient Treated with Intravenous Vasoactive Intestinal Peptide

RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) has been granted Fast Track Designation by the US FDA for the treatment of Critical COVID-19 with Respiratory Failure. We describe the clinical course of the first patient treated with this investigational medication in an open label manner -- a 54 year old patient suffering antibody-mediated rejection of his double lung transplant who contracted COVID-19 with respiratory failure refractory to all currently available therapies. He received three infusions of RLF-100 under an FDA-approved emergency use IND. Within 24 hours of the third infusion, substantial improvement in oxygen saturation and radiographic improvement in characteristic COVID-19 pneumonitis was noted. He was discharged from intensive care at that point and returned home at 1 week on room air.

Advances in Antibody–Drug Conjugate Design: Current Clinical Landscape and Future Innovations

The targeted delivery of potent cytotoxic molecules into cancer cells is considered a promising anticancer strategy. The design of clinically effective antibody–drug conjugates (ADCs), in which biologically active drugs are coupled through chemical linkers to monoclonal antibodies, has presented challenges for pharmaceutical researchers. After 30 years of intensive research and development activities, only seven ADCs have been approved for clinical use; two have received fast-track designation and two breakthrough therapy designation from the Food and Drug Administration. There is continued interest in the field, as documented by the growing number of candidates in clinical development. This review aims to summarize the most recent innovations that have been applied to the design of ADCs undergoing early- and late-stage clinical trials. Discovery and rational optimization of new payloads, chemical linkers, and antibody formats have improved the therapeutic index of next-generation ADCs, ultimately resulting in improved clinical benefit for the patients.

Faster approvals?: Trends in the use of FDA’s expedited approval programs for oncology medications.

e18270 Background: With the importance of speed-to-market and addressing unmet needs, pharmaceutical companies have sought accelerated approvals through the Food and Drug Administration (FDA). Introduced with the FDA Safety and Innovation Act (FDASIA) of 2012, Breakthrough Therapy Designation (BTD) has become an important mechanism for approval of serious and life-threatening conditions that do not have adequate therapies. Notably, these pathways have been ill-understood by both pharmaceutical companies and health care providers. This study assessed how BTD and other FDA designations have played a role in the approval of oncology drug marketing applications and evaluated trends in the use of these regulatory pathways. Methods: We analyzed publicly available data on novel oncology drug approvals by the FDA from 2012-2016, including the 4 expedited programs for serious conditions (BTD, Accelerated Approval, Fast Track, and Priority Review). Results: Of the 43 novel oncology drugs approved by the FDA between 2012-2016, 42 used at least 1 of the expedited approval programs, including 65% that used ≥2 programs and 35% that used ≥3 programs. The BTD has been used by 15 of the 43 (35%) approved novel oncology drugs since 2012. The use of the BTD, Accelerated Approval pathway, and Priority Review designation among approved oncology drugs has generally increased each year from 2012-2016, while the use of the Fast Track designation has decreased over the same time period. Conclusions: Companies seeking oncology approvals often use more than one expediting strategy. Alone or in combinations, the BTD, Accelerated Approval, and Priority Review have been shown to play an increasingly important role in oncology drug development. Data collected between 2012-2016 suggest that use of BTD is growing more common, while use of the Fast Track designation has decreased among approved oncology drugs. Additional expedited approval programs have remained steady or increased since the FDA introduced BTD. Based on these observations, we anticipate use of the BTD, Accelerated Approval, and Priority Review designation will grow in future oncology drug applications.