Hopes continue to rise as the COVID-19 vaccine beat goes on and Operation Warp Speed (OWS) lives up to its name, with Moderna Inc. netting another U.S. Department of Defense contract worth about $1.97 billion for another 100 million doses – an order that brings to about $6 billion the company’s government contracts for the product, which was granted emergency use authorization (EUA) earlier this month.
At the same time, vaccine straggler Novavax Inc., of Gaithersburg, Md., became the fifth company to launch a late-stage study, kicking off the phase III trial called PREVENT-19 with its NVX-CoV2373. The prospect contains a full-length, prefusion spike protein made using recombinant nanoparticle technology designed by Novavax plus the company’s saponin-based Matrix-M adjuvant. It can neither cause COVID-19 nor replicate, is stable at 2°C to 8°C and is shipped in a ready-to-use liquid formulation that permits distribution using standard vaccine supply chain channels, the firm noted.
Despite its new-kid status, NVX-CoV2373 has gained hearty endorsement from the likes of Jefferies analyst Kelechi Chikere, who started coverage of Novavax Dec. 14 and called the vaccine entrant “well positioned” in the space. She said Novavax could “benefit from recent vaccine landscape shakeup. Following the release of controversial results by [London-based Astrazeneca plc], there are outstanding questions, including the true efficacy of its vaccine and next steps.” The findings rolled out by Astrazeneca “suggest a minimum threshold of neutralizing antibodies [nAb] required to provide protection, and Novavax’s is arguably the only dataset to show nAb levels [that are] similar to better” than the mRNA vaccines. New York-based Pfizer Inc. with partner Biontech SE, of Mainz, Germany, with BNT162b2 and Moderna with mRNA-1273 have set a high bar that others – except Novavax – may not be able to reach, in her view.
In a more recent (Dec. 29) report, Chikere continued to sound optimistic, recognizing that the Novavax phase III push is put together similarly to those conducted by Pfizer and Cambridge, Mass.-based Moderna. With support from OWS, the venture is expected to enroll up to 30,000 volunteers across 115 sites in the U.S. and Mexico. Like experiments overseen by Moderna and Pfizer, Novavax will sign up at least 25% subjects age 65 years or older and at least 25% from diverse communities. Volunteers will be randomized to receive two injections of NVX-CoV2373 or placebo, 21 days apart. The primary endpoint will assess the prevention of polymerase chain reaction-confirmed, symptomatic COVID-19 seven days after the second shot. Interim peeks will happen when 50% (72 symptomatic infections) and 75% (108 symptomatic infections) of the total 144 needed for the final analysis occur. There’s a slight difference from one of the mentioned competitors in this respect. Interim exams and the final analysis in the Moderna bid were planned at 53, 106, and 151 cases, but the first interim look had 95. The study will use the same independent data and safety monitoring board to monitor safety and assess efficacy as the other phase III studies conducted under the OWS aegis.
“We continue to think there is a high likelihood [75%-plus probability] that the vaccine will demonstrate high efficacy, similar to Moderna and Pfizer, given the high neutralizing antibody titers observed in the phase I/II study,” Chikere said.
Urgency, guidance changing
A big question has to do with whether Novavax will be able to enlist and keep volunteers, with two vaccines already in active play and more data coming not only from Astrazeneca but also Whitehouse Station, N.J.-based Johnson & Johnson – which has a phase III trial called Ensemble ongoing with its single-dose vaccine – in January or February of 2021. Some tweaks made to the NVX-CoV2373 trial architecture may help; Novavax is giving two-thirds of enrollees active vaccine, as compared to the one-to-one randomization in other OWS phase IIIs, and the firm will zero-in on areas where COVID-19 infections are especially high. Also, recruitment sites have been established in Mexico, where mRNA vaccinations are getting done, but slowly. Novavax has another potential leg up: The firm is finishing up volunteer studies in the UK (about 15,000 subjects) and in South Africa (about 4,500) – territories where the virus is rampant now – with data due in the first quarter of next year. Also ahead in the first quarter of 2021 are data from phase I/II research in the U.S. and Australia, due to include immunogenicity findings in elderly subjects.
In separate news, the FDA posted an update regarding the dosage of the vaccine from Pfizer and Biontech, also distributed by way of an EUA. Regulators advise using every full dose obtainable – the sixth, or even a seventh – from each vial, but not mixing leftovers from vials to create a dose, since the product contains no preservative. The agency cautioned that no data are available on the interchangeability of this vaccine with the others, so the second dose should be the same product as the first. The two companies also announced they will supply 100 million additional doses of Comirnaty, the companies’ COVID-19 vaccine, to the 27 EU member states in 2021. The EC exercised its option to purchase an additional 100 million doses under an advanced purchase agreement signed on Nov. 11, 2020. It brings the total number of doses to be delivered to the EU to 300 million.
News emerged from an earlier-stage soldier in the COVID-19 vaccine army. San Diego-based Arcturus Therapeutics Holdings Inc. suffered a stock-walloping setback with its one-injection, self-replicating mRNA wannabe ARCT-021. After the markets closed Dec. 28, the company unveiled interim data from the phase I/II study in 106 healthy volunteers. Arcturus said peak geometric mean titers for nAb at day 29 across three phase II doses ranged from 32 to 46, “which is worrisome to us, as these levels are negligible and are unlikely to confer any meaningful antiviral protection,” Wainwright analyst Ed Arce wrote in a report. “Overall, we have lost confidence” in the vaccine’s potential, he said, downgrading shares of the firm to neutral with a $50 price target. Arcturus (NASDAQ:ARCT) closed at $42.36, down $50.06, or 54.2%.
Laidlaw’s Yale Jen kept the faith. “We view the news as encouraging,” he said in a report, allowing that a separate phase II experiment by Arcturus might be necessary, given the outcomes from multiple relatively small size cohorts of the phase I/II. “The level of urgency and guidance for a successful vaccine may be different from that of six months ago,” he added. “We view the potential immunity driver by T cells logical and interesting, and anticipate future clinical outcomes to validate this hypothesis.”
Focus on stability
Arcturus CEO Joseph Payne said during a conference call with investors that it will be “interesting to see how the scientific community compares ours to others. Some people will say [it’s] equivalent,” and some may spy a “superior immunogenicity profile after a single administration. But clearly, there's proof in the pudding that, in multiple challenge models in mice and in primates, and even in animals that are severely deficient in immune responses and the ability to create nAb titers, we've seen success.”
Other up and comers in the evolving landscape include Dartmouth, Nova Scotia-based IMV Inc., with preclinical DPX-COVID-19, a formulation of the DPX delivery platform with four complementary peptide antigens. DPX is described as a “no-release” lipid-based delivery strategy without an aqueous component in the final formulation. This means no elements are let go at the injection site, so the vaccine can continuously interact with and stimulate the immune system over an extended period.
IMV on Dec. 28 touted safety, GLP toxicology as well as immunogenicity, and underlined challenge studies that clarified the vaccine’s favorable profile and its potential to generate long-lasting antibody titers (up to 140 days). Wainwright analyst Joseph Pantginis likes the story, saying in a report that “the novel, though clinically validated mechanism of action, the lyophilized formulation with long-term stability (at least three months at 4-8°C), and the capacity for large-scale manufacturing and supply could make DPX-COVID-19 an attractive vaccine candidate for global-scale development.”
Inovio Inc., of Plymouth Meeting, Pa., recently talked up the publication of favorable, peer-reviewed phase I data from the first cohort of 40 participants for its COVID-19 DNA vaccine candidate, INO-4800, in an open access clinical journal published by The Lancet. The company has underway the phase II segment of its planned phase II/III trial. INO-4800 stays stable at room temperature for over a year and at 37°C for over a month, and does not need to be frozen during transportation or storage, which should make it easier to distribute far and wide, vs. the mRNA-based headliners that require cold chain logistics. Wainwright’s Raghuram Selvaraju’s Dec. 28 report was cautiously upbeat, as he stuck to his neutral rating on the shares, “given the nature of the competitive landscape and uncertainty” about how the vaccines may ultimately work in the real world.