Novavax electrified investors last night by announcing that its COVID-19 vaccine NVX-CoV2373 showed efficacy of 89.3% in the company’s first analysis of data from a Phase III trial in the U.K., where a variant strain (B.1.1.7) accounted for about half of all positive cases.

However, NVX-CoV2373 achieved only 60% efficacy in a Phase IIb trial in South Africa, where that country’s escape variant of the virus (B.1.351, also known as 20H/501Y.V2) was seen in 90% of cases, Novavax said.

“NVX-CoV2373 is the first vaccine to demonstrate not only high clinical efficacy against COVID-19 but also significant clinical efficacy against both the rapidly emerging U.K. and South Africa variants,” Stanley C. Erck, Novavax’s president and CEO, said in a statement.

Erck’s statement offered no details about the company’s timing for pursuing U.S. regulatory approvals, starting with an emergency use authorization (EUA) from the FDA. The company began a rolling submission to the U.K.’s regulatory agency, the Medicines and Healthcare products Regulatory Agency (MHRA), earlier this month.

However, investors appeared to share Erck’s positive assessment of both trials, sending Novavax’s shares rocketing nearly 27% in after-hours trading, to $170 a share as of 7:59 p.m. Thursday, from that day’s closing price of $134.01.

“With these results in hand, we think NVAX will be able to file for emergency use authorization (or its equivalent) in multiple territories,” Kelechi Chikere, PhD, equity analyst at Jefferies, and colleagues wrote Thursday in a research note. “Given how good the data look, we think at a minimum NVAX should be able to discuss w/ the FDA a potential EUA [emergency use authorization] filing based on these data vs. the ongoing Phase III.”

Chikere cited past comments by officials with Operation Warp speed—the Trump administration-launched U.S. government effort to advance development of COVID-19 vaccines and drugs—suggesting that companies could pursue alternative strategies for EUA filings, “which in our view could mean ex-U.S. studies like NVAX’s Phase III U.K. study could be used to file to the FDA.”

NVX-CoV2373 is a stable, prefusion protein made using Novavax’ nanoparticle technology, and incorporating its proprietary saponin-based Matrix-M™ adjuvant. NVX-CoV2372  is one of 21 “Front Runner” candidates among the more than 300 COVID-19 therapeutics included in GEN’s updated “COVID-19 Drug & Vaccine Candidate Tracker.”

$1.6B from Washington

Operation Warp Speed awarded $1.6 billion in July to Novavax toward R&D efforts related to NVX-CoV2373, including the Phase III studies.

Novavax’s interim analysis of U.K. data was based on 62 COVID-19 cases, of which 56 were seen in the placebo group and six, in the group randomized to NVX-CoV2373. Of the 62 COVID-19 cases, all but one were mild or moderate, with the sole severe case occurring in the placebo group.

The U.K. variant strain was seen in more than 50% (32 of 62) PCR-confirmed symptomatic cases. Another 24 symptomatic cases were non-variant, and six were unknown. Based on PCR performed on strains from 56 of the 62 cases, Novavax said, the efficacy of its vaccine by strain was 95.6% against the original COVID-19 strain and 85.6% against the U.K. variant strain [post hoc].

“These are spectacular results, and we are very pleased to have helped Novavax with the development of this vaccine. The efficacy shown against the emerging variants is also extremely encouraging,” stated Clive Dix, chair, U.K. Vaccine Taskforce. “This is an incredible achievement that will ensure we can protect individuals in the U.K. and the rest of the world from this virus.”

The U.K. trial enrolled more than 15,000 participants between 18–84 years of age, including 27% over the age of 65. The trial’s primary endpoint is based on the first occurrence of PCR-confirmed symptomatic (mild, moderate, or severe) COVID-19 with onset at least seven days after the second study vaccination in serologically negative (to SARS-CoV-2) adult participants at baseline.

South African trial

In the South Africa trial, the 60% efficacy in preventing mild, moderate, and severe COVID-19 disease was seen in the 94% of the study population that was HIV-negative.

“The lower ~60% efficacy seen with the South African variant may be a point of concern. We’d argue, however, that ~60% efficacy is still okay and may be enough to slow down infections enough for MRNA to implement and develop a variant targeted strategy (as it is currently doing),” Chikere’s colleague at Jefferies, Equity Analyst Michael J. Yee, wrote in a separate research note.

“To do this in a regulatory environment that’s seemingly conducive for quick approval is great for MRNA. Bottom line, we think MRNA is in a good position to tackle new variants and this may be a notion that’s being appreciated by folks thinking about 2022+ and boosts as the stock is +30% in the last week,” Yee added.

Of the positive cases, 29 were seen in the placebo group, and 15 in the group randomized to NVX-CoV2373. All but one of the positive COVID-19 cases were mild or moderate. The sole severe case occurred in the placebo group.

In the overall trial population, including HIV-positive and HIV-negative subjects, the efficacy rate was 49.4%, which according to Novavax met the trial’s primary efficacy endpoint.

The South African trial study enrolled more than 4,400 patients beginning in August 2020, with COVID-19 cases counted from September through mid-January. The South African “triple mutant” variant, which contains three critical mutations in the receptor-binding domain (RBD) and multiple mutations outside the RBD, was widely circulating in South Africa during the trial, Novavax said.

Preliminary sequencing data is available for 27 of the 44 COVID-19 cases. Of these events, 92.6% (25 of 27 cases) were the South Africa escape variant.

Pre-trial infections

Approximately one-third of the patients enrolled in the South African trial but not included in the primary analyses showed prior COVID-19 infection at baseline. Those pre-trial infections are thought to have been caused by the original COVID-19 strain while the subsequent infections during the study were largely variant virus, Novavax said, citing temporal epidemiology data in the region.

The data suggested that prior infection with COVID-19 may not completely protect against subsequent infection by the South Africa escape variant, Novavax acknowledged—but added that vaccination with NVX-CoV2373 provided “significant” protection.

Novavax said additional analysis on both South African and U.K. trials is ongoing and will be shared via prepublication servers as well as submitted to a peer-reviewed journal for publication.

NVX-CoV2373 is also under study in the Phase III PREVENT-19 (PRE-fusion protein subunit Vaccine Efficacy Novavax Trial, COVID-19) trial being conducted in the United States and Mexico. PREVENT-19 (NCT04611802) has randomized more than 16,000 participants to date—more than halfway toward the study’s enrollment goal. The randomized, placebo-controlled, observer-blinded study is designed to assess the efficacy, safety, and immunogenicity of NVX-CoV2373 in up to 30,000 participants 18 years of age and older compared with placebo. The trial’s primary endpoint is the prevention of PCR-confirmed, symptomatic COVID-19.

“NVX-CoV2373 has the potential to play an important role in solving this global public health crisis,” Erck said. “We look forward to continuing to work with our partners, collaborators, investigators, and regulators around the world to make the vaccine available as quickly as possible.”

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