After a month-long clinical hold, Novavax has received the green light from the US Food and Drug Administration (FDA) to resume clinical trials for its Covid-19 and influenza combination vaccine (CIC) and standalone influenza vaccines.
The FDA initially halted the trials on 16 October after a patient in the Phase II trial (NCT05519839) of the CIC vaccine candidate was diagnosed with motor neuropathy, later reclassified as amyotrophic lateral sclerosis (ALS), a rare neurodegenerative condition. After evaluating the data, the FDA concluded that the ALS diagnosis was unrelated to Novavax’s vaccine.
With the regulatory hold lifted, Novavax is now preparing to initiate a Phase III study (NCT06291857) of both the CIC vaccine – named NVX-CoV2373 – and a new, standalone flu vaccine called tNIV. Novavax’s chief medical officer Robert Walker said that the FDA “satisfactorily addressed all clinical hold issues.” Walker confirmed that trial activities will resume as soon as possible.
Novavax’s upcoming Phase III trial will evaluate the efficacy of the CIC vaccine in adults aged 65 and older by comparing its immune response against those produced by standard flu and COVID-19 vaccines. The trial will also investigate the effectiveness of Novavax’s investigational flu vaccine tNIV against standard-of-care Fluzone High-Dose.
The trial will involve nearly 8,000 participants in two parts: the first will focus on immune response and side effects, while the second will further monitor safety outcomes. The company is aiming to commence enrolment by the end of 2024 and have preliminary results by mid-2025. The CIC vaccine could represent an opportunity for Novavax, which faced market challenges against established Covid-19 vaccine leaders like Pfizer and Moderna. However, Novavax’s Covid-19 vaccine experienced limited adoption after its US launch in July 2022. This led to significant cost-cutting, including a 30% workforce reduction in 2023 and early 2024, and a “going concern” warning about its operational future, citing uncertainties around sales and US government funding.
In response to these challenges, Novavax has undertaken significant financial restructuring, with plans to cap combined R&D and SG&A spending below $500m in 2025 and under $350m by 2026, as per Novavax’s Q2 2024 financial report.
The company has also pursued strategic partnerships, securing a $1.2bn licensing agreement with Sanofi in May 2024 to co-commercialize its standalone adjuvanted COVID-19 vaccine, which bolsters Novavax’s position as it advances the CIC and other vaccine programmes.
Pfizer-BioNTech and Moderna are also racing to develop combination COVID-19 and influenza vaccines. In June 2024, Moderna took the lead with its candidate mRNA-1083, which produced “statistically significantly higher immune responses” than existing vaccines in a Phase III trial (NCT06097273).
Meanwhile, Pfizer and BioNTech encountered a setback as their combo vaccine failed to meet one of its two primary endpoints in a Phase III trial (NCT06178991) in August. While the vaccine demonstrated high responses for neutralizing influenza A titres, it failed to show sufficient efficacy against influenza B.