Steering Zuventus Towards Success

Passionate, determined, and focused are the virtues that describe Prakash Guha but do not define him. He has grown from strength to strength in the pharma industry and carved a space for Zuventus, an entity that he co-founded with Mr. Satish Mehta, over two decades ago. Reminiscing his early days, he shared that in 2002, he and some of his colleagues decided to become a part of Emcure, while working autonomously. This led to the germination of the present day, 1000 crore business - Zuventus.

Humble Beginnings: In the initial phase, when these budding entrepreneurs were contemplating various ideas, Mr. Satish Mehta, Founder and CEQ, Emcure Group, came into the picture. That is when Zuventus began to take shape. Mr. Guha avers, “To start with, Zuventus got a few brands worth 12-15 crore from Emcure to Zuventus. At that time, these brands were not that big, but we thought we needed a vehicle to move before we could steer towards success. Later, we started launching our own brands.”

People Power: One thing that has remained constant between then and now for Zuventus, is its people. Company's employee strength has grown ten folds from a starting count of 350 to a 3,500 strong workforce. Zuventus has seen many ups and downs, and Mr. Guha firmly believes that it wouldn't have been possible to reach current heights without the outstanding team at Zuventus, who are ready to fight every situation and bounce back.

When the world was grappling with the COVID-19 crisis, Zuventus was one of the few companies that remained buoyant. Mr. Guha shared, “Some of our brands did well and turned the tide in our favour. The marketing team, sales force, and all other functions played a crucial role during these times.

Zuventus became a household name with products like Zinconia and Scavista used for the treatment of COVID. While we have built a strong product portfolio, | believe the success wouldn't have come without the hard work and dedication of every Zuventian.”

Diverse Portfolio: Emcure's research and development capabilities have helped Zuventus launch many new molecules and products, many of which were introduced for the first time in India. “The diversified product portfolio helped Zuventus build a strong position in the market. We have established a strong position in the majority of the therapies in which we have apresence.”

Zuventus currently has four major divisions. The largest of them is the multispecialty division. Second is Grow Max, which is a specialty division in gastro as well as respiratory. Then is Odenea and finally, the cardio diabetic division, which is a lifestyle division. There are two other divisions of generics and vaccines where itis increasing its presence.

Abstract

Aim: This study is aimed at evaluating efficacy and safety of Intravenous Aviptadil as an add-on to the “Standard of Care” treatment in severe COVID-19 patients with respiratory failure. Design, Setting and Participants: A randomized, multicentric, double-blind, placebo-controlled, comparative Phase III clinical trial was conducted at 8 geographically distributed sites across India between April 2021 to October 2021. The study enrolled 150 participants who were tested and confirmed cases of severe COVID-19 with respiratory failure and acute respiratory distress syndrome. Interventions: 12-hour intravenous infusions of Aviptadil over 3 successive days in ascending doses given as 0.166 mcg/kg/hr on Day 1 (equivalent to one 10 mL vial of 150 mcg), 0.332 mcg/kg/hr on Day 2 (equivalent to two 10 mL vials of 150 mcg each) and 0.498 mcg/kg/hr on Day 3 (equivalent to three 10 mL vials of 150 mcg each). Methodology: Severe COVID-19 patients with respiratory failure were randomized in two groups in a ratio of 1:1, to receive either Aviptadil or Placebo. Both the study drugs were given as an add-on to the standard of care (SOC). The SOC was kept as close as possible to the COVID-19 treatment guidelines specified by the Government of India. The study site staff, investigator and patients were masked to the treatment allocation. The primary endpoint of the study was resolution of respiratory failure whereas the secondary endpoints were improvement in WHO 7-point ordinal scale, improvement in PaO2:FiO2 ratio, survival of the patients and incidences of adverse events. Results: After the completion of treatment in Aviptadil group, an improvement was observed in the primary outcome of resolution of respiratory failure. Proportion of patients on Aviptadil demonstrated statistically significant odds, 2.1-fold, (p=0.0410) of being free of respiratory failure (no oxygen requirement) at Day 3 and 2.6-fold (p=0.0035) at day 7 as compared to the placebo group. An earlier resolution from the respiratory failure, with a median duration of 7 days was noted in the Aviptadil-treated group as compared to 14 days in the placebo group. A higher proportion of patients on Aviptadil shifted to the milder clinical state (32.43% vs 17.80%; p=0.0410 on Day 3 and 70.27% vs 45.21%; 0.0035 on Day 7) without the requirement of oxygen than the placebo group. A reduction of severity (based on WHO 7-point ordinal scale) in clinical status were also observed on Day 14 (p = 0.0005 by Wilcoxon rank sum test) and Day 28 (p = 0.0009 by Wilcoxon rank sum test). There were 68.42% Aviptadil-treated patients who showed 2 or more points improvement on the WHO 7-point ordinal scale as compared to 44.59% in the placebo group (p=0.003; Pearson chi2 test; odds ratio, 2.69; 95% CI, 1.38-5.24) on Day 7. On day 28, patients in the Aviptadil group had higher odds (1.38) of an improvement on WHO 7-point ordinal scale as compared to placebo with SOC. Aviptadil reduced the risk of death by 20% (relative risk 0.80; 95% CI: 0.35, 1.66) in ARDS. Patients treated with Aviptadil demonstrated significant improvement in PaO2/FiO2 ratio vs. placebo from day 2 to over the week (p<0.05) and beyond. There were 15 deaths in the Aviptadil group and 18 deaths in the placebo group. No deaths were attributed to the Investigational products. COVID-19–related mortality occurred in 22% patients of the study population, due to respiratory failure caused by underlying medical conditions. Conclusion: Use of Aviptadil was safe and effective in improving the resolution of respiratory failure, shortening the time to recovery, decreasing respiratory distress and preventing death in respiratory failure patients. The rapidity and magnitude of clinical effect suggests a highly specific role of Aviptadil in combating the lethal effects of Acute Respiratory Distress Syndrome associated with COVID-19.

KEYWORDS: COVID-19, Vasoactive Intestinal Peptide (VIP), Acute Respiratory Distress Syndrome (ARDS), Acute Lung Injury (ALI), Alveolar Type II.

Zuventus Health care has been recognised as one of the “Most Preferred Workplace 2022-23 Health & Wellness” organised by Team Marksmen in association with India Today.  The event held at held in Mumbai on Friday 23 December’22.

The award recognises and celebrates organizations that have successfully maximized employee wellbeing, engagement and productivity alongside organizational performance. It features organizations that have excelled in reorienting the commercial landscape, and have also seen them prioritise an employee experience by adopting people practices aligned with the business and fostering caring, learning and engaging workplace.

Organizations are appraised on the parameters such as Employee Centricity, Organizational Purpose, Work Flexibility, Diversity and Equality, Growth and Rewards, and Social Cohesion.

Abstract

Aim: This study is aimed at evaluating the efficacy and safety of Intravenous Glutathione in moderate COVID-19 patients with respiratory distress.

Study Design: A randomized, multicentric, double-blind, placebo-controlled, comparative Phase III clinical trial.

Place and Duration of Study: This clinical trial was conducted at 7 geographically distributed sites across India between February 2021 to September 2021.

Participants: The study enrolled 240 participants who were tested and confirmed cases of moderate COVID-19 with respiratory distress.

Interventions: Intravenous glutathione (GSH) at a loading dose of 2400 mg on the first day, followed by a dose of 1200 mg every 12 hours for seven days.

Methodology: Patients were randomized into two groups in a ratio of 1:1, to receive either glutathione or placebo. Both the study drugs were given as an addition to the standard of care (SOC). The study site staff, investigator and patients were blinded to the treatment allocation. The primary endpoint of the study was two or more points of improvement on the WHO 7-point ordinal scale whereas the secondary endpoints were the proportion of patients not requiring oxygen supplementation after treatment. Other secondary endpoints included the proportion of patients who changed from a higher to a lower score on the WHO 7-Point ordinal scale, the proportion of patients remaining hospitalized, the need of non-invasive ventilation or new requirement of high flow oxygen use, and incidences of adverse events.

Results: A significant clinical improvement in the GSH group (p<0.001) was observed in early treatment days. On day 3, GSH group had improvement in 49.15% of the patients as compared to 31.96% on placebo (p=0.007; odds ratio, 2.06; 95% CI, 1.22-3.48). A higher proportion of patients with baseline score of 5 or more in the GSH group (64.63%) showed improvement as compared to the placebo (46.58%) (p=0.024; odds ratio, 2.10; 95% CI, 1.10-4.00). A higher proportion of patients in the GSH group attained a score of 3 or less signifying no need of Oxygen supplementation, as compared to the placebo group on Day 2, Day 3 and Day 4. A reduction of severity in clinical status was also observed on Day 3, Day 4 and Day 5. The risk of remaining in the hospital was reduced by 37% in the GSH group. The 7-day dose of GSH was well tolerated by the patients.

Conclusion: GSH supplementation reduces the cytokine storm and respiratory distress in patients with COVID-19 pneumonia. GSH can also be used for treating respiratory distress due to other etiologies due to its favorable safety profile. GSH treatment should also be explored in a larger number of patients with ARDS of varied etiologies in randomized trials.

Abstract

Aim: This study aimed at evaluating the efficacy and safety of a fixed-dose combination (FDC) of Efonidipine and Chlorthalidone in a randomized, Phase III trial setting.

Study Design: Multicentric, randomized, double-blind, parallel, comparative, active-controlled Phase III.

Place and Duration of Study: Six geographically distributed sites across India were involved in this trial.

Methodology: Present study enrolled patients of Indian origin who were diagnosed with Stage I or Stage II hypertension as per JNC VII guideline. A total of 240 hypertensive patients were randomized (1:1) to receive either FDC of Efonidipine 40 mg + Chlorthalidone 12.5 mg tablet (E+C group) or FDC of Cilnidipine 10 mg + Chlorthalidone 12.5 mg tablet (C+C group) once daily for 90 days. The study site staff, investigator and patients were blinded to the treatment allocation. Patients were evaluated for changes in their blood pressure (BP) from baseline to Day 30, 60 and 90. BP was recorded as the mean of 3 consecutive measurements taken in a sitting position. the number of patients achieving target BP as per JNC VIII guideline was also evaluated. The safety and tolerability were assessed based on the incidences of adverse events (AEs) and serious adverse events (SAEs) reported.

Results: The mean (±SD) Systolic BP (SBP) and Diastolic BP (DBP) at baseline was 159.10±11.43/101.19±10.03 mmHg in the E+C group. After 30 days of treatment with the E+C group, the mean (±SD) reduction in SBP/DBP of 25.13±16.23/16.11±10.35 mmHg was observed whereas at Day 60 reduction of 32.51±19.73/17.91±11.06 mmHg was seen from baseline. The primary endpoint focused on evaluating the mean BP reduction from baseline at Day 90. As compared to baseline, BP decreased from 159.10±11.43/101.19±10.03 mmHg to 118.95±15.31/ 81.59±3.78 mmHg with a mean reduction of 40.15/19.60 mmHg at day 90 in the E+C group. The secondary endpoint of target BP <140/90 mmHg attainment as per JNC VIII guideline, was also achieved in 90.99% of the patients given the E+C group regimen. Furthermore, it was observed that 94% of Stage I and 88% of Stage II hypertensive patients achieved the target BP goal. Overall, 2.54% of patients from the E+C group reported adverse events (AEs) which were mild in severity and resolved without any sequelae at the end of the study. No unexpected AEs were reported, and the E+C group regimen was well tolerated.

Conclusion: It was concluded that the FDC of Efonidipine 40 mg and Chlorthalidone 12.5 mg was efficacious in the management of hypertension in both Stage I and Stage II hypertensive patients. It was evident from the study results that clinically meaningful reductions in blood pressure were observed over a period of 90 days. The test drug was safe and well tolerated by the patients after being administered as a single tablet daily.