Most Americans no longer view COVID-19 as a major threat to health, a Pew Research Center poll found earlier this month—but the virus is still top of mind to investors in two developers of vaccines designed to offer protection, judging from the significant swings in opposite directions shown by the companies’ stock prices.
Valneva (VALN) shares dropped 21% during trading on Wednesday from $21.99 to $17.40, before settling for a 9% one-day decline to $18.56 at the closing bell. The decline followed the European Commission slashing its order for doses of Valneva’s inactivated whole-virus COVID-19 vaccine VLA2001. The order was slashed from the 60 million doses agreed upon through an Advance Purchase Agreement (APA) in November 2021 (of which 27 million were to be delivered this year), to just 1.25 million doses for delivery in August and September, with an option to procure another 1.25 million doses.
The Commission cited the availability of other COVID-19 vaccines and a slowdown in vaccination programs since the November 2021 agreement.
The slashing of the order came nearly a month after the European Commission granted full marketing authorization to VLA2001, which consists of inactivated whole virus particles of SARS-CoV-2 with high S-protein density, in combination with two adjuvants, alum and Dynavax’s CpG 1018. The authorization covered all 28 European Union Member States as well as Iceland, Liechtenstein, and Norway. Since VLA2001 has a shelf life of up to 24 months, Valneva said, it will aim to deploy the doses in the next six to 12 months.
“We welcome the fact that the EC has decided not to terminate the APA, although we feel the order volume does not reflect the interest we see from European citizens,” Valneva CEO Thomas Lingelbach said in a statement. “Despite this, we have decided to enter into this amendment to make our vaccine available to the Europeans who have been waiting for it.”
Valneva has cited May statistics from the European Medicines Agency showing that 15% of Europeans over 18 were not yet vaccinated. “We continue to receive messages from Europeans who are awaiting a more traditional vaccine technology,” Lingelbach said.
Valneva is counting on more such messages given a recent surge in COVID-19 cases across Europe which has been blamed on Omicron variants, chiefly BA.5: “While the pandemic had been declining, the latest COVID-19 wave in Europe clearly underlines the need for alternative vaccines,” the CEO added.
The slashing of the European order was one of several factors why Jefferies lowered its one-year price target for Valneva stock to $34 a share from $56 last month, though the firm maintained its “Buy” rating. “Lower EC interest could make sense, given current landscape,” analyst Maury Raycroft, PhD, wrote in a recent research note.
Raycroft also cited the success of another COVID-19 vaccine developer, Novavax (NVAX), in winning European approval for its vaccine, with an agreement to provide 100 million doses to the EU. The vaccine is being marketed in Europe as Nuvaxovid™.
Earlier this month, Novavax won Emergency Use Authorization (EUA) from the FDA for the Novavax COVID-19 Vaccine, Adjuvanted (NVX-CoV2373) for use in individuals age 18 and older. (The trade name has yet to be approved in the U.S.). NVX-CoV2373 is a stable, prefusion protein made using Novavax’ proprietary nanoparticle technology, and incorporating its proprietary saponin-based Matrix-M™ adjuvant.
Investors have responded by sending Novavax shares on a month-long roller-coaster ride. From a low of $34.71 on June 14, Novavax shares more than doubled, soaring 119% to $76.12 on July 8, before falling 8% to $69.95 on July 13, the day of the FDA EUA, as investors pondered how much of a foothold Novavax would gain vs. larger competitors Pfizer/BioNTech, Moderna, and to a lesser extent Johnson & Johnson.
Shares have yo-yoed since then, sinking 26% over three trading days to $51.97 on Monday before climbing again, rising 12% to $58.00 on Tuesday and up another 3% to $59.57 on Wednesday, a day after the U.S. Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices’ (ACIP) recommended that Novavax’s COVID-19 vaccine be used as another primary series option for adults ages 18 years and older—as Jefferies analyst Roger Song, MD, CFA, expected in a research note Tuesday.
Novavax CEO Stanley C. Erck cited positive data showing that his company’s vaccine demonstrated 90.4% efficacy in the pivotal Phase III PREVENT-19 trial (NCT04611802), which enrolled approximately 30,000 participants aged 18 years and over in the U.S. and Mexico, with a favorable safety profile.
“This authorization reflects the strength of our COVID-19 vaccine’s efficacy and safety data, and it underscores the critical need to offer another vaccine option for the U.S. population while the pandemic continues,” Erck stated.
Adial Pharmaceuticals (ADIL)
Adial shares tumbled 46% on Wednesday, falling from $1.84 to $99 cents a share after acknowledging that its AD04 showed a non-statistically significant reduction in the pre-specified primary efficacy endpoint of its Phase III ONWARD trial (NCT04101227) assessing the genetically targeted serotonin-3 receptor antagonist AD04 in adults with alcohol use disorder (AUD) and selected polymorphisms in the serotonin transporter and receptor genes.
That endpoint was the change from baseline in the monthly number of (heavy) drinking days during the last 8 weeks of the 24-week treatment period, where (heavy) drinking was defined as the consumption of ≥ 60 g alcohol/day for males, or ≥ 40 g alcohol/day for females.
ONWARD recruited patients with specified target genotypes (estimated to be approximately one-third of the AUD population), who were identified using the company’s proprietary companion diagnostic genetic test.
According to Adial, those AD04 patients showed a reduction from baseline “trend” at month six in heavy drinking days that was influenced by high placebo response among very heavy drinkers (avg. ≥10 drinks per drinking day at baseline), as both the AD04 and placebo groups were shown to have reduced mean heavy drinking days by more than 50%. A “similar, non-statistically significant trend” was seen, Adial added, in the combined months five and six analysis in the reduction from baseline—the trial’s pre-specified primary efficacy analysis.
Adial highlighted more positive data from ONWARD—such as a mean reduction of approximately 79% in heavy drinking compared with baseline in AD04-treated heavy drinking patients during the last month of the trial. AD04 also showed a statistically significant difference in AUD severity vs. placebo, with an 84% decrease in the number of heavy drinking patients meeting the criteria for AUD diagnosis, the company said.
“Based on the strength of these ONWARD results in heavy drinking patients that have the target genetics, and the fact that AD04 demonstrated an exceptional safety profile, and was well-tolerated during the trial, we intend to advance AD04,” Adial CEO William Stilley said in a statement. “We will work with regulatory authorities in Europe and the U.S. to achieve this goal. We also plan to explore strategic partnerships.”
Apellis Pharmaceuticals (APLS)
Apellis shares started Tuesday by surging 23.5% to $55.36, then rose to a 26% gain and $56.48 at 10::30 a.m. before settling by the end of trading for a 16% increase and a closing price of $52.06. The surge followed Apellis’ announcement that the FDA had accepted and granted Priority Review designation for the New Drug Application (NDA) of intravitreal pegcetacoplan.
Pegcetacoplan is a targeted C3 therapy designed to treat geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The FDA set a Prescription Drug User Fee Act (PDUFA) target action date of November 26, 2022—and is not, according to the company, planning to hold an advisory committee meeting to discuss the application.
Systemic pegcetacoplan is marketed under the name Empaveli®, which last year won FDA approval as a treatment for paroxysmal nocturnal hemoglobinuria (PNH)—creating a commercial challenge to longtime PNH leader Alexion (now an AstrtaZeneca subsidiary), whose two blockbusters dominate the space.
“Priority review/no AdCom bodes well for approval, in our view,” Colleen M. Kusy, CFA, Senior Research Analyst with Baird, wrote Wednesday in a research note outlining what she acknowledged was “a more-positive-than-expected scenario.”
“While the package is not without risk, we think there is certainly enough supportive data to justify approval, and the FDA’s current posturing is a positive signal,” Kusy added. She reiterated Baird’s “Outperform” rating on Apellis shares.
Sesen Bio (SESN)
Shares of Sesen Bio plummeted 32% on Monday, from $0.90 to $0.616, after the company said it was voluntarily pausing its development in the U.S. of Vicineum, the company’s lead candidate being developed as a treatment for non-muscle invasive bladder cancer (NMIBC). The company said its decision was based on talks with the FDA as well as a “thorough” reassessment of Vicineum, including its incremental development timeline and associated costs for an additional Phase III trial in NMIBC.
“We have had four productive meetings with the FDA since August 2021 and we believe we have a full understanding of the FDA’s evolving position and guidance on the following variables: accelerated versus standard approval, single-arm versus randomized controlled trials, comparative versus non-comparative efficacy endpoints, and adequate versus less-than-adequate BCG patient populations,” said Thomas Cannell, DVM, Sesen Bio’s President and CEO.
Cannell added that the company had also seen the current treatment paradigm in NMIBC change as a result of the ongoing shortage of Bacille Calmette-Guérin, a standard of care for many patients with NMIBC for decades, with increased uptake of intravesical chemotherapy (monotherapy and combination therapy).
Sesen said its decision will save the company cash while it evaluates potential strategic alternatives to maximize shareholder value. As of June 30, Sesen said, it had $161.2 million in cash and cash equivalents, down 5% from $169.79 million as of March 31, but up nearly 7% from $151.036 million a year earlier.
VBL Therapeutics (VBLT)
VBL Therapeutics shares cratered 79% on Wednesday, from $2.05 to $0.425 a share, the first trading day after the company acknowledged that its lead oncology candidate ofra-vec (ofranergene obadenovec; VB-111) failed the Phase III OVAL trial (NCT03398655) by not meeting the primary endpoints of achieving a statistically significant improvement in progression-free survival (PFS) or overall survival (OS).
VBL said it plans to halt OVAL, a randomized, double-blind, placebo-controlled trial designed to compare the combination of ofra-vec and paclitaxel to placebo and paclitaxel in 409 adult patients with recurrent platinum-resistant ovarian cancer. Patients randomized to ofra-vec and paclitaxel had a median PFS of 5.29 months, compared with 5.36 months for placebo plus paclitaxel. The interim overall survival analysis was also not significantly different between the two study arms, with the treatment arm showing a median OS of 13.37 months vs. 13.14 months in the control arm—a finding that according toVBL did not support study continuation.
“Given the urgent unmet need for those fighting platinum-resistant ovarian cancer, we are deeply disappointed that the top-line data indicate that ofra-vec did not improve progression free survival or overall survival,” VBL Therapeutics CEO Prof. Dror Harats, MD, said in a statement.
So too was H.C. Wainwright, whose analyst Swayampakula Ramakanth downgraded the company’s shares from “Buy” to “Neutral.”
Harats said VBL will review data from its ongoing Phase II trials in metastatic colorectal cancer and recurrent glioblastoma multiforme to determine next steps for ofra-vec, which combines vascular disruption designed to starve a tumor’s blood supply with an immuno-oncology approach intended to bring T-cells to the tumor.
OVAL was conducted in collaboration with the GOG Foundation, an independent international non-profit organization with the purpose of promoting excellence in the field of gynecologic malignancies.