Coronavirus Update: Pfizer/BioNTech Vaccine Effective Against Omicron

Also, AstraZeneca scores an emergency use authorization from the FDA for its COVID-19 PrEP antibody Evusheld, while Merck files for Japanese approval of molnupiravir.

 

Comirnaty Shows 'Encouraging' Activity Against Omicron

The likelihood that most people will need at least a third dose of Pfizer Inc. and BioNTech SE’s messenger RNA-based COVID-19 vaccine Comirnaty became more apparent as the companies announced data showing that a third dose provided neutralized antibody titers against the new Omicron variant, while the standard two-dose series showed significantly reduced neutralization.

The remaining question now is how effective other vaccines are against Omicron, especially amid lingering fears that the variant’s spread could lead to renewed lockdowns and other restrictions.

The data announced 8 December indicate a third dose of Comirnaty increased neutralizing antibody titers by 25-fold compared with two doses against Omicron, also known as B.1.1.529, with titers after the booster dose comparable to those observed after two doses against the wild-type virus strain, which are associated with high levels of protection.

In a same-day press conference, BioNTech CEO Ugur Sahin noted that in addition to the efficacy of third doses of the wild-type vaccine, variant-specific versions of the vaccine have also produced strong responses with equal tolerability.

“We have observed … that the booster dose with these variant vaccines on top in individuals who had previously received two doses of the BioNTech/Pfizer vaccine induces strong neutralizing antibody responses equal to or even higher than those observed with boostering with the wild-type vaccine,” he said. “Particularly interesting is that boostering individuals who have received a boostering with the Alpha variant have had a more than 400% increase [in] neutralizing antibody levels against the Omicron variant, which would be in line with the fact that the Alpha variant shares multiple mutations with the Omicron variant.”

In a same-day note, Mizuho Securities analyst Vamil Divan said the neutralizing antibody data appear “encouraging.”

“We are encouraged by what the companies have shared, most notably data suggesting the level of neutralizing antibodies seen to Omicron after a third dose of Comirnaty is similar to what was seen with two doses to the wild-type and other variants,” Divan said. “In conjunction with initial data out of South Africa suggesting Omicron may be causing milder disease, we think this bodes well for our ability to mitigate the impact of Omicron with the tools we already have, while likely increasing patient demand for initial vaccinations and booster shots.”

Moderna, Inc. has also announced a strategy to address Omicron, saying on 26 November that it would evaluate the efficacy of a 100mcg booster of its original mRNA-1273 vaccine against the variant, while also testing a variant-specific candidate, mRNA-1273.529, along with two multi-valent booster candidates designed to anticipate mutations like those in Omicron, mRNA-1273.211 and mRNA-1273.213.

Johnson & Johnson also said 29 November that it is testing the efficacy of its vaccine against Omicron. (Also see "COVID-19 Vaccine Makers Pledge Rapid Response To Omicron Threat" - Scrip, 29 Nov, 2021.)

AstraZeneca’s Evusheld Gets COVID-19 PrEP Nod

AstraZeneca PLC’s Evusheld (tixagevimab/cilgavimab) will play a key role among COVID-19 drugs as a pre-exposure prophylaxis (PrEP) drug, following US Food and Drug Administration emergency use authorization, although it may find itself confined amid the potential for competition from more established players.

The FDA granted the EUA on 8 December for Evusheld, which consists of two monoclonal antibodies packaged together and administered as consecutive intramuscular shots, for people aged 12 and older and weighing at least 40kg. The EUA covers people with moderate-to-severe immune compromise due to medical conditions or use of immunosuppressive medications who are unable to mount an adequate immune response after vaccination against COVID-19, as well as people for whom vaccination is not recommended.

The EUA is based on data from the Phase III PROVENT trial, which showed a statistically significant 77% reduction at primary analysis announced in August and an 83% reduction at six months in the risk of developing symptomatic COVID-19 compared with placebo, with protection from the virus continuing for at least six months. (Also see "GSK/Vir’s Xevudy Begins EU Review For COVID-19" - Pink Sheet, 19 Nov, 2021.)

While Evusheld showed strong results as a PrEP drug for COVID-19, it has not fared so well as a treatment for people already infected. While the drug has shown some efficacy in preventing progression to more severe disease, the 50% reduction in risk is significantly less than from Regeneron Pharmaceuticals, Inc./Roche Holding AG’s REGEN-COV, Vir Biotechnology, Inc./GlaxoSmithKline plc’s Xevudy (sotrovimab) or Eli Lilly and Company’s bamlanivimab/etesevimab.

As such, AstraZeneca said in October it would position Evusheld as a preventative. (Also see "AstraZeneca Shrugs Off COVID Antibody’s Inferiority In Therapy Setting, Sees Prevention As Main Role" - Scrip, 11 Oct, 2021.)

Although REGEN-COV is not currently authorized for pre-exposure prophylaxis, on 8 November Regeneron announced data from a 1,683-participant Phase III trial showing that the drug produced an 81.5% reduction in the risk of contracting SARS-CoV-2 during an eight-month period. (Also see "Could Prevention Data Give REGEN-COV Competitive Leg Up?" - Scrip, 8 Nov, 2021.)

Thus, if REGEN-COV eventually manages to win an EUA for PrEP use, Evusheld’s narrower market opportunity could place the AstraZeneca drug at a disadvantage.

Merck & Co Files For Molnupiravir In Japan

MSD (Merck & Co., Inc.) said on 3 December it had filed for the approval in Japan of the oral COVID-19 antiviral molnupiravir, under an emergency accelerated pathway being granted to new drugs and vaccines for the coronavirus pandemic. 

The new Japanese filing could result in a marketing authorization by the end of the year, although it is not yet clear what the precise indication might be. In the UK, the first country globally to approve molnupiravir in early November (as Lagevrio), the drug was cleared for use in those with mild to moderate COVID-19 symptoms and at least one risk factor for developing severe illness.

The Japanese submission is based on existing clinical data for the twice-daily ribonucleoside analog, which include an interim analysis of part two of the MK-4482-002 Phase III trial, in which 775 outpatients were randomized to receive 800mg of molnupiravir or placebo for five days. All-cause hospitalization or death in this interim population through Day 29 was 7.3% for molnupiravir and 14.1% for placebo; the relative risk reduction for molnupiravir was 48%.

Subsequently updated top-line safety and efficacy results from the full population of 1,433 randomized participants showed that all-cause hospitalization or death through Day 29 was 6.8% for molnupiravir and 9.7% for placebo; the relative risk reduction for molnupiravir compared to placebo was 30%. 

The Merck drug, developed with Ridgeback Biotherapeutics LP, is pending a US emergency use authorization (EUA) after a narrowly positive advisory committee meeting in late November.  (Also see "Divided US FDA AdComm Backs Molnupiravir Authorization But Wants More Studies" - Pink Sheet, 30 Nov, 2021.)

Besides vaccines, a total of five drug or antibody treatments have so far been approved in Japan under a Special Approval for Emergency system (the equivalent of an EUA), as provided for under Article 14-3 (Paragraph 1) of the Pharmaceuticals and Medical Devices Act. This enables rapid approval (typically within weeks) for emergency public health needs if the products are already approved in countries with regulatory systems comparable to Japan’s.

Molnupiravir now looks set to become the first of the new oral antivirals for COVID-19 to be approved in the country and would be able to be home administered following an appropriate prescription. The Japanese government has already contracted with Merck for the supply of around 1.6 million courses (which usually last five days), in a contract the US firm said was valued at around $1.2bn including taxes.

Other working on oral antivirals include Pfizer Inc. with Paxlovid, a combination of the 3CL protease inhibitor PF-007321332 and ritonavir, which showed an 89% reduction in risk of death for non-hospitalized infected patients at high risk of progression to severe illness and is also awaiting a US EUA.

Japanese firm Shionogi & Co. Ltd. is progressing a placebo-controlled Phase II/III study in a planned 2,000 mild or asymptomatic COVID-19 patients in Japan with its contender S-217622, a 3CL protease inhibitor, which has shown effectiveness in a once-daily regimen.

An emergency use approval filing could come for this in Japan by the end of this year, depending on the data available at the time.