US Food and Drug Administration (FDA) Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted 12 to 1 that the data presented support the use of Entresto® (sacubitril/valsartan) in treatment of patients with heart failure with preserved ejection fraction (HFpEF). This was based on data supporting the benefit of Entresto in reducing worsening heart failure (total heart failure [HF] hospitalizations and urgent HF visits) in patients studied in PARAGON-HF. If approved by the FDA, Entresto could become the first therapy indicated for use in treatment of patients with HFpEF, as well as the first medication approved for both major types of chronic heart failure, HFpEF and heart failure with reduced ejection fraction (HFrEF), both based on trials that included active comparators (valsartan and enalapril, respectively).
With no approved therapies for HFpEF to address the prevention of HF hospitalizations and urgent visits, a significant unmet medical need exists for a treatment to reduce the burden associated with this debilitating condition. The FDA is expected to make a decision on the supplemental New Drug Application (sNDA) in the first quarter of 2021.
“Managing HFpEF has historically been a clinical and scientific challenge due to the heterogeneity of the condition,” said Scott Solomon, MD, Professor of Medicine at Harvard Medical School and Brigham and Women's Hospital, and PARAGON-HF Executive Committee Co-Chair. “Today’s vote represents much needed progress in this area of unmet need and is a positive step toward bringing a potential therapy to millions of patients suffering from this type of heart failure.”
The Committee’s positive decision is based on the totality of evidence from efficacy and safety analyses, including findings presented from a pre-specified subgroup analysis of PARAGON-HF, the largest and only Phase III active-controlled study to date in patients with HFpEF and additional evidence from PARAMOUNT (a Phase II trial in HFpEF), as well as PARADIGM-HF (a Phase III trial in HFrEF). Data from PARAGON-HF demonstrated a favorable safety profile for Entresto in patients with HFpEF, which is in line with the vast clinical and post-marketing experience in HFrEF, and showed clinical benefit of Entresto in HFpEF patients.
“Our commitment to reimagine medicine through our extensive clinical trials program on heart failure has been unwavering, and we are encouraged by the Committee’s response today,” said David Soergel, MD, Global Head of Cardiovascular, Renal and Metabolic Drug Development, Novartis. “We appreciate the valuable insights shared by the patient and advocacy community about this devastating disease, and we look forward to FDA’s decision on the potential approval of this new indication.”
HFpEF affects more than 3 million Americans, and is increasing in prevalence as the population ages. It is a complex disease for which it is difficult to develop treatments due to its heterogeneous pathophysiology and the varied impact of symptoms among patients, despite decades of research. HFpEF can change the structure of the heart and occurs when the muscle tissue of the heart thickens and stiffens so that it cannot expand to fill with enough blood to meet the body’s needs. HFpEF is associated with high rates of recurring heart failure hospitalizations, emergency room visits and urgent doctor’s office appointments. Each hospitalization event is associated with worsening long-term prognosis, and approximately one in four patients are re-admitted for heart failure within one year of discharge.
Aurobindo Pharma Limited is pleased to announce that the company has received final approval from the US Food & Drug Administration (USFDA) to manufacture and market Dexmedetomidine Hydrochloride in 0.9% Sodium Chloride Injection, 200 μg/50 mL and 400 μg/100 mL Single Dose flexible containers (Bags).
Aurobindo’s Dexmedetomidine HCl in 0.9% Sodium Chloride Injection is a therapeutic equivalent generic version of Hospira’s Precedex® in 0.9% Sodium Chloride Injection. The product will be launched in January 2021.
Dexmedetomidine Hydrochloride in 0.9% sodium chloride injection is a relatively selective alpha2 -adrenergic agonist indicated for a) sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care setting; b) sedation of non-intubated patients prior to and/or during surgical and other procedures. The approved product has an estimated market size of US$ 228 million for the twelve months ending October 2020 according to IQVIA.
This is the 79th ANDA to be approved out of Unit IV formulation facility in Hyderabad, India used for manufacturing injectable & ophthalmic products. Aurobindo now has a total of 459 ANDA approvals (431 Final approvals and 28 tentative approvals) from USFDA.
The Russian Direct Investment Fund (RDIF, Russia’s sovereign wealth fund), and Hetero, one of India’s leading generic pharmaceutical companies (through its biologics arm “Hetero Biopharma”) have agreed to produce in India over 100 million doses per year of the world’s first registered vaccine against the novel coronavirus infection – Sputnik V.
The parties intend to start the production of Sputnik V in the beginning of 2021.
The Gamaleya Center and RDIF announced on November 24 positive results obtained during the second interim data analysis of the largest double-blind, randomized, placebo-controlled Phase III clinical trials in Russia’s history involving 40,000 volunteers. Interim trial results have once again confirmed the high efficacy of the Sputnik V vaccine, the world’s first registered vaccine against coronavirus based on a well-studied platform of human adenoviral vectors. Evaluation of efficacy was carried out among volunteers (n = 18,794) 28 days after receiving the first dose (7 days after the second dose) of the vaccine or placebo upon reaching the second control point of the trial in compliance with the clinical trial protocol. The analysis demonstrated a 91.4% efficacy rate for the Sputnik V vaccine.
The uniqueness of the Russian vaccine lies in the use of two different vectors based on the human adenovirus, which allows for a stronger and longer-term immune response as compared to vaccines using one and the same vector for two doses. So, preliminary data on volunteers on the 42nd day after the first dose (equivalent to 21 days after the second dose), when they have already formed a stable immune response, indicates the efficacy rate of the vaccine is above 95%.
Currently Phase III clinical trials are approved and are ongoing in Belarus, the UAE, Venezuela and other countries, as well as Phase II-III in India. Requests for more than 1.2 billion doses of Sputnik V vaccine came from more than 50 countries. The vaccine supplies for the global market will be produced by RDIF’s international partners in India, Brazil, China, South Korea and other countries.
The safety of vaccines based on human adenoviruses has been confirmed in more than 75 international publications and more than 250 clinical trials conducted during the past two decades - while the history of use of human adenoviruses in vaccine development started in 1953. Adenovirus vectors are genetically modified viruses of the regular flu that cannot reproduce in a human body. When the Sputnik V vaccine is used, the coronavirus itself does not enter the body as the vaccine only contains genetic information about part of its outer protein coat, the so called "spikes" forming its crown. This completely eliminates the possibility of getting infected as a result of vaccination while also causing the body's stable immune response.
Kirill Dmitriev, CEO of the Russian Direct Investment Fund, commented:
“We are delighted to announce the agreement between RDIF and Hetero that will pave the way to production of the safe and highly effective Sputnik V vaccine on Indian soil. The vaccine’s interim clinical trial results show 95% efficacy on the 42nd day after the first dose. I am confident that Sputnik V should become an integral part of the national vaccine portfolio of every country willing to protect its population from the coronavirus. Thanks to our cooperation with Hetero, we will be able to significantly increase production capacity and provide people of India with an efficient solution in this challenging period of the pandemic”.
B. Murali Krishna Reddy, Director – International Marketing, Hetero Labs Limited commented:
“We are pleased to collaborate with RDIF as a manufacturing partner for the most anticipated Sputnik V vaccine for the treatment of Covid-19. While we look forward to the clinical trial results in India, we believe that manufacturing the product locally is crucial to enable swift access to patients. This collaboration is another step towards our commitment in the battle against Covid-19 and realizing the objective of ‘Make-in-India’ campaign as envisioned by our Hon’ble Prime Minister of India.”
AstraZeneca’s Imfinzi (durvalumab) has been approved in the US for an additional dosing option, a 1,500mg fixed dose every four weeks, in the approved indications of unresectable Stage III non-small cell lung cancer (NSCLC) after chemoradiation therapy (CRT) and previously treated advanced bladder cancer. This new option is consistent with the approved Imfinzi dosing in extensive-stage small cell lung cancer (ES-SCLC) and will be available to patients weighing more than 30kg as an alternative to the approved weight-based dosing of 10mg/kg every two weeks.
The approval by the Food and Drug Administration (FDA) was based on data from several Imfinzi clinical trials, including the PACIFIC Phase III trial which supported the two-week, weight-based dosing in unresectable Stage III NSCLC, and the CASPIAN Phase III trial which used four-week, fixed-dosing during maintenance treatment in ES-SCLC. The decision follows the Priority Review granted by the FDA in August 2020.
Victoria M. Villaflor, MD, Clinical Professor in the Department of Medical Oncology and Therapeutics Research at City of Hope Cancer Center, Los Angeles, California, said: “This new four-week dosing option gives doctors the choice to cut the number of visits for critical cancer treatment in half and offers a regimen that is more convenient for patients. Additionally, it limits potential exposure to infection in the healthcare environment for a population that is especially vulnerable to complications from COVID-19.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: “The approval of this new dosing option across indications reflects our ongoing commitment to improve the patient experience and ensure continuity of care - a priority at all times, but especially during the pandemic. Cancer won’t wait, and it is our job to provide patients with treatment options that acknowledge the challenges the pandemic poses to cancer care, enabling them to visit their physician when truly needed and avoid preventable exposure to healthcare-associated infections.”
The four-week 1,500mg fixed-dosing option for Imfinzi is also under regulatory review in several other countries, including in the EU where the new dosing option was granted accelerated assessment.
Imfinzi is approved in the curative-intent setting of unresectable, Stage III NSCLC after CRT in the US, in the EU, in Japan, in China and in many other countries, based on the PACIFIC Phase III trial. Imfinzi is also approved for previously treated patients with advanced bladder cancer in the US and several other countries. Additionally, it is approved in the US, the EU, Japan and several other countries around the world for the treatment of ES-SCLC based on the CASPIAN Phase III trial.
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