Search This Blog

Thursday, December 31, 2020

Brazil biomedical center to seek emergency use of British COVID-19 vaccine

 Brazil’s Fiocruz biomedical center will request authorization for emergency use of the COVID-19 vaccine developed by AstraZeneca PLC and Oxford University by next Wednesday, its president, Nísia Trindade, said on Thursday.

She said approval of the vaccine in Britain on Wednesday will speed up the regulatory green lights for the vaccine in Brazil, where it is badly needed to fight the world’s second deadliest coronavirus outbreak.

“To avoid delays, and on the basis of authorization in Britain, we decided to also put in the request for emergency use of the vaccine,” she said in an interview.

Brazil, whose right-wing President Jair Bolsonaro is a coronavirus skeptic who says he won’t have a vaccine, has fallen behind neighbors Chile and Argentina where vaccination is already underway. No vaccine has been approved in Brazil yet.

Filing for registration of the British vaccine with health regulator Anvisa cannot be finalized before Jan. 15 as paperwork is still being prepared, such as production control documents for the vaccine, which the federally funded Fiocruz plans to make from scratch at its Rio de Janeiro facility.

“I am optimistic that vaccination can start by the end of January or beginning of February,” Trinidade said.

Fiocruz expects to deliver the first 1 million doses between Feb. 8 and Feb. 12, though that will depend on the arrival of the active pharmaceutical ingredient for the vaccine scheduled for Jan. 9, Trindade said.

By the end of February, Fiocruz plans to have delivered 10 million doses, and from then it will be putting out 3.5 million doses a week, for a total 100 million fill-and-finish doses in the first half of 2021.

In April or May, Fiocruz will have a parallel production line going to make the vaccine entirely in Brazil, though that will still require Anvisa validation, she said. The goal is to deliver 110 million doses in the second half of the year.

Trindade expects Brazil to stick to two-dose vaccination, since the evidence that 1-1/2 doses is more effective still requires further studies worldwide by AstraZeneca.

But she does expect Brazil’s National Immunization Program to separate the two jabs by a 12-week interval, which researchers in Britain have found to be more effective.

The vaccine costs $4 per dose: $3.15 paid to AstraZeneca and the rest for the fill-and-finish process. Fiocruz does not yet have an estimated cost for the vaccine made in Brazil.

Fast-spreading U.K. virus variant raises alarms

 On 8 December 2020, a small group of scientists in the United Kingdom logged on for a regular Tuesday videoconference about the spread of the pandemic coronavirus. The discussion focused on Kent, a county in southeastern England that was seeing increasing transmission of SARS-CoV-2, even as the rest of the country was managing to curb the spread. Because investigations had not found any obvious causes—no big workplace outbreaks or changes in people's behavior—several researchers had been asked to look at viral genomes from the region.

The genetic family tree they presented showed something unusual was going on, says one of the attendees, microbial genomicist Nick Loman of the University of Birmingham. Not only were half the cases in Kent caused by a specific variant of SARS-CoV-2, but its branch literally stuck out from the rest of the data. “I've not seen a part of the tree that looks like this before,” Loman says. And when scientists compared how fast this variant, named B.1.1.7, and others were spreading, they made a startling discovery: The virus seemed to have become more adept at transmitting between people.

The discovery of the viral lineage, along with a similarly worrying one in South Africa, had a massive impact. On 19 December, U.K. Prime Minister Boris Johnson announced that London and southeastern England would be placed under tighter COVID-19 restrictions to contain the variant, which Johnson said may be 70% more transmissible. Although there's no evidence yet that the strain is more deadly, many countries closed their borders to travelers from the United Kingdom as they mulled how to deal with the possible new threat. Several announced they, too, had the variant among their populations.

As this issue of Science went to press on 23 December, scientists were still grappling to understand whether the variant really spreads faster, and if so, how. But its emergence had driven home the notion that viral evolution, which so far has had little impact on the trajectory of the COVID-19 pandemic, could yet result in nasty surprises—just as the first effective vaccines are being rolled out. It also raises the question of whether those vaccines may need periodic updating to parry a changing virus.

The U.K. lineage of SARS-CoV-2 has apparently acquired 17 mutations that lead to amino acid changes in its proteins all at once, a feat never seen before in the coronavirus. Crucially, eight of them were in the gene that encodes spike, a protein on the viral surface that the pathogen uses to enter human cells. “There's now a frantic push to try and characterize some of these mutations in the lab,” says Andrew Rambaut, a molecular evolutionary biologist at the University of Edinburgh.

Three already stand out as worrisome. A mutation named N501Y has previously been shown to increase how tightly spike binds to the angiotensin-converting enzyme 2 receptor, its main entry point into human cells. Scientists in South Africa were the first to spot N501Y's importance: They noted it several weeks ago in a lineage that is surging in the Eastern Cape, Western Cape, and KwaZulu-Natal provinces. “We found that this lineage seems to be spreading much faster,” says Tulio de Oliveira, a virologist at the University of KwaZulu-Natal whose work alerted U.K. scientists to the mutation. That's concerning, says evolutionary biologist Jesse Bloom of the Fred Hutchinson Cancer Research Center: “Anytime you see the same mutation being independently selected multiple times, it increases the weight of evidence that that mutation is probably beneficial in some way for the virus.”

B.1.1.7's second notable mutation, a deletion named 69-70del, leads to the loss of two amino acids in the spike protein. It, too, had appeared before: It was found, together with another mutation named D796H, in the virus of a COVID-19 patient in Cambridge, U.K., who was given plasma from recovered patients as a treatment, but eventually died. In lab studies, the patient's strain was less susceptible to convalescent plasma from several donors than wild-type virus, says Ravindra Gupta, a virologist at the University of Cambridge who published the findings in a preprint in early December.

Gupta also engineered a lentivirus to express mutated versions of SARS-CoV-2's spike and found that the deletion alone made the virus twice as infectious for human cells. A third mutation, P681H, is one to watch as well, says virologist Christian Drosten of the Charité University Hospital in Berlin, because it changes the site where the spike protein is cleaved before it enters human cells.

Embedded Image

The mutation N501Y affects amino acids (yellow) in the spike protein, which binds to a human receptor (green).


New virus strains are common in outbreaks and often spark alarm, but few are ultimately consequential. So U.K. scientists and others were initially cautious about concluding that B.1.1.7's mutations made the virus better at spreading from person to person. But the new variant is rapidly replacing other viruses, says Müge Çevik, an infectious disease specialist at the University of St. Andrews. Yet exactly what impact each mutation has is much more difficult to assess than spotting them or showing they're on the rise, says Seema Lakdawala, a biologist at the University of Pittsburgh.

Animal experiments can help show an effect, but they have limitations. Hamsters already transmit SARS-CoV-2 virus rapidly, for instance, which could obscure any effect of the new variant. Ferrets transmit it less efficiently, so a difference may be more easily detectable, Lakdawala says. “But does that really translate to humans? I doubt it.” A definitive answer may be months off, she predicts.

The slew of mutations also raised worries that the South African or U.K. lineage might lead to more severe disease or even evade vaccine-induced immunity. So far there is little reason to think so. Whereas some mutations have been shown to let the virus evade monoclonal antibodies, vaccines and natural infections both appear to lead to a broad immune response that targets many parts of the virus, says Shane Crotty of the La Jolla Institute for Immunology. “It would be a real challenge for a virus to escape from that.” The measles and polio viruses have never learned to escape the vaccines targeting them, he notes: “Those are historical examples suggesting not to freak out.”

At a 22 December press conference, BioNTech CEO Uğur Şahin pointed out that the U.K. variant differed in only nine of more than 1270 amino acids of the spike protein encoded by the messenger RNA in the very effective COVID-19 vaccine his company developed with Pfizer. “Scientifically it is highly likely that the immune response by this vaccine also can deal with the new virus,” he said. Experiments are underway that should soon confirm that, Şahin added.

Another major question is how the virus accumulated a host of mutations in one go. So far, SARS-CoV-2 typically acquired only one to two mutations per month. Scientists believe the new variant may have gone through a lengthy bout of rapid evolution in a chronically infected patient who then transmitted the virus. “We know this is rare but it can happen,” says World Health Organization epidemiologist Maria Van Kerkhove.

Sébastien Calvignac-Spencer, an evolutionary virologist at the Robert Koch Institute, says the United Kingdom's new COVID-19 lockdown and other countries' border closures mark the first time such drastic action has been taken based on genomic surveillance in combination with epidemiological data. “It's pretty unprecedented at this scale,” he says. But the question of how to react to disconcerting mutations in pathogens will crop up more often, he predicts. Most people are happy they prepared for a category 4 hurricane even if the predictions turns out to be wrong, Calvignac-Spencer says. “This is a bit the same, except that we have much less experience with genomic surveillance than we have with the weather forecast.”

To Van Kerkhove, the arrival of B.1.1.7 shows how important it is to follow viral evolution closely. The United Kingdom has one of the most elaborate monitoring systems in the world, she says. “My worry is: How much of this is happening globally, where we don't have sequencing capacity?” Other countries should beef up their efforts, she says. And all countries should do what they can to minimize transmission of SARS-CoV-2 in the months ahead, Van Kerkhove adds. “The more of this virus circulates, the more opportunity it will have to change,” she says. “We're playing a very dangerous game here.”

Top 2020 Biopharma M&A Deals

 The year 2020 will certainly go down in history as the year of COVID-19. And while a large portion of the biopharmaceutical world pivoted their pipelines to address the novel coronavirus, that didn’t halt a number of high profile mergers and acquisitions.

BioSpace highlights a number of the key M&A deals struck over the past 12 months.

Gilead Sciences Makes Multiple Bets: When Gilead Sciences wasn’t working on remdesivir in COVID-19, the company seemed to be constantly flexing its M&A muscle over the course of 2020. It began in May with the $4.9 billion acquisition of immuno-oncology company Forty Seven and its lead asset, magrolimab, a monoclonal antibody in the clinic for several cancers, including myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and diffuse large B-cell lymphoma (DLBCL). Magrolimab targets CD47. In addition to magrolimab, Forty Seven had been driving two other candidates into the clinic, FSI-174, an anti-cKIT antibody, being studied in combination with magrolimab as a novel, all-antibody regimen to assist in stem cell transplantation conditioning regimens, and FSI-189, an anti-SIRP alpha antibody for cancer as well as certain non-oncology settings, including transplantation conditioning.

Gilead Sciences wasn’t done with its dealmaking. In September, the company moved deeper into oncology with the $21 billion acquisition of Immunomedics. That company’s breast cancer treatment Trodelvy, which was granted accelerated approval from the U.S. Food and Drug Administration in April for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease, is expected to become a cornerstone of Gilead Science’s oncology business alongside magrolimab and the CAR-T drug Yescarta, which it gained through its acquisition of Kite Pharma.

In December, Gilead shifted from bolstering its oncology business and strengthened its liver disease pipeline with the $1.4 billion acquisition of Germany-based Myr GmbH, a company focused on developing therapies for treatment of chronic hepatitis delta virus (HDV), the most severe form of viral hepatitis. The acquisition brings Myr’s chronic HDV treatment Hepcludex (bulevirtide) under its umbrella. Hepcludex is an entry inhibitor that binds to NTCP, an essential HBV and HDV receptor on hepatocytes.

AstraZeneca Dives into Rare Diseases: AstraZeneca has been in the spotlight for the COVID-19 vaccine candidate it developed with Oxford University. But the U.K.-based company made waves in December when it acquired Alexion Pharmaceuticals and its rare diseases platform in a $39 billion deal. For AstraZeneca, the acquisition paves a new frontier for its pipeline. AstraZeneca has primarily been focused on oncology, cardiovascular, renal and metabolism and respiratory diseases.

Alexion’s focus is on inhibition of the complement system. The company has a number of branded products in this space, including Soliris (eculizumab), a first-in-class anti-complement component 5 (C5) monoclonal antibody. Soliris has been approved for paroxysmal hemoglobinuria (PNH), atypical hemolytic uremic syndrome, generalized myasthenia gravis and neuromyelitis optica spectrum disorder. Another of its branded assets is Ultomiris (ravulizumab), a second-generation C5 monoclonal antibody.

Earlier this year, Alexion acquired Portola Pharmaceuticals and its blood disorder treatments for $1.4 billion. Alexion said the acquisition of Portola will bolster its commercial portfolio and create long-term value for its shareholders. The deal brings Portola’s Andexxa [coagulation factor Xa (recombinant), inactivated-zhzo] under its umbrella. Andexxa, was approved by the U.S. Food and Drug Administration in 2018 and is currently the only approved Factor Xa inhibitor reversal agent.

Johnson & Johnson Buys Up Momenta – Life sciences giant J&J acquired Momenta Pharmaceuticals in a $6.5 billion all-cash deal to bolster subsidiary Janssen’s immune-mediated diseases business and drive further growth through expansion into autoantibody-driven disease. As BioSpace previously reported, the asset at the center of the deal is Momenta’s lead candidate nipocalimab, an aglycosylated, effectorless IgG1 anti-FcRn monoclonal antibody that won both Orphan Drug designation and Rare Pediatric Disease designation for the prevention of hemolytic disease of the fetus and newborn (HDFN), a serious blood disorder in a fetus or newborn that occurs when red blood cell incompatibility exists between the blood types of a mother and fetus in utero.

When the deal was struck, J&J said nipocalimab provides the company with an opportunity to reach more patients by pursuing indications across many autoimmune diseases with substantial unmet medical need in maternal-fetal disorders, neuro-inflammatory disorders, rheumatology, dermatology and autoimmune hematology.

Nestlé and Peanut Allergies – In August, Nestlé Health Science acquired the outstanding stakes of Aimmune for $2.6 billion in cash to gain control of FDA-approved Palforzia, a first-of-its-kind treatment for patients with peanut allergies. Nestlé Health Science has a history of advancing nutritional therapies. Many of the food products developed by Nestlé contain allergens, including peanuts, so it has made sense the company would support those companies aiming to curb allergic reactions to food products. Nestlé has been a longtime partner of Aimmune, first investing in the company in 2016.

Following the acquisition, Nestlé said Aimmune will serve as the point pharmaceutical business for Nestlé Health Science. The new global business expands Nestlé Health Science’s growth strategy to span a breadth of offerings from with a pharmaceutical business added to its medical nutrition and consumer care offerings. As Aimmune moves forward in this new endeavor, the California-based company said it will maintain its focus on expanding the indication for Palforzia to toddlers and adults, as well as focus on the development of the monoclonal antibody AlMab7195 as a potential treatment of other food allergies.

10 Biopharma Stories to Look Forward to in 2021

 If 2020 taught us anything, it was that unexpected things happen. That said, there are some stories we’ll be watching for. Here’s a look.

  1. The end of the pandemic. In 2020, it’s safe to say that the pandemic was far worse than expected—although maybe not as bad as it could have been—and very difficult to predict. Now that in the U.S. and Europe there are two vaccines, with other vaccines, such as Sinovac’s and Russia’s Sputnik V, being deployed in other parts of the world, the expectations are that in 2021 the COVID-19 pandemic will come under control and potentially basically disappear—although most experts seem to believe “under control” is a more likely outcome in the shorter term.

Scott Gottlieb, former director of the U.S. Food and Drug Administration (FDA), noted in December 2020 that he expected the pandemic could “effectively” be ended in 2021 with the launch of the Pfizer-BioNTech and Moderna vaccines. He and others have suggested it will largely be under control by summer, although there are likely to be flare-ups in the Fall.

  1. AstraZeneca and University of Oxford COVID-19 vaccine authorization. Early on in the race for a vaccine against COVID-19, AstraZeneca and the University of Oxford’s efforts were leading the way with expectations of being the first to be authorized. In September 2020, the trials were halted to investigate a potentially severe side effect in a UK patient, transverse myelitis, an inflammation of part of the spinal cord. After a short break, the trial restarted in the UK and other parts of the world, but was delayed for much longer in the U.S.

Then in early December, AstraZeneca and the University of Oxford published interim data analysis of their four Phase III trials of their vaccine, with some confounding results. They reported overall efficacy of 70.4%, which was quite a bit lower than that seen with the Pfizer-BioNTech and Moderna vaccines, which were both around 95%. But further confusing the issue was that about 1800 participants accidentally received a first dose that was only about half the intended dose. But in those participants, the efficacy was about 90%, while in the broader dosing regimen it was 62%. The reason for this is still not understood and many regulators may want it to be explained before authorizing it for broader use.

As of December 27, 2020, the UK government was reviewing vaccines from both AstraZeneca and Moderna. Approximately 40% of the AstraZeneca-Oxford vaccine has been reserved for low- and middle-income countries.

  1. Johnson & Johnson’s COVID-19 vaccine. On December 17, 2020, Johnson & Johnson, which is running probably fourth for U.S. and European COVID-19 vaccine development, announced their Phase III ENSEMBLE trial was fully enrolled with about 45,000 participants. They hope to have interim data from the trial available by the end of January 2021, and if it is safe and effective, plans to submit for Emergency Use Authorization (EUA) to the FDA in February, with other global health regulators following immediately afterwards. One of the reasons this is promising is that unlike the other three vaccines mentioned above, the J&J vaccine only needs a single dose—at least that’s the theory so far. If everything goes well, then there would be a single-dose vaccine that could be widely deployed, which would require less manufacturing and more manageable storage than the others. The Pfizer-BioNTech vaccine requires extremely cold storage temperatures, with the Moderna requiring more typical freezing temperatures found in standard refrigerators.
  2. Biogen’s aducanumab. One way or the other, Biogen’s aducanumab for Alzheimer’s disease is likely to be a big story in 2021. In March 2019, Biogen and its collaboration partner, Tokyo-based Eisai, announced they were discontinuing the ENGAGE and EMERGE Phase III trials of the drug in patients with mild Alzheimer’s because it wasn’t likely to hit the primary endpoints. Then, in July, after analyzing completed data and with talks with the FDA, they decided they were going to pursue regulatory approval for the drug. In early December 2019, they presented full data at the 12th Clinical Trials on Alzheimer’s Disease (CATD) conference. The company argued that the Phase III EMERGE trial met its primary endpoint, demonstrating a significant decrease in clinical decline in a subset of patients that received a high enough dose of the drug.

In November 2020, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee voted 1 yes, 8 no, and 2 uncertain on the question of whether the EMERGE trial provided evidence that supported the effectiveness of aducanumab. Other similar questions also had similar votes. In short, the advisory committee did not vote to recommend the drug to the agency, which has a PDUFA date of March 7, 2021 to decide whether to approve the aducanumab Biologics License Application (BLA).

  1. Biden Administration and drug pricing. At this point, incoming President Joe Biden has announced plans to lower drug prices building on the foundations of the Affordable Care Act. Some his plans include repealing the rules that prevent drug companies from directly negotiating with Medicare over drug prices. And he wants to limit the launch prices of new drugs that have no competition and “are being abusively priced by manufacturers.” The Biden plan also calls for Health and Human Services to establish an independent review board to assess the value of a new drug. The board will then recommend a “reasonable price” based on the average price in other countries or, if the drug is entering the U.S. market first, based on an evaluation by the independent board members.

Another Biden plan opens up foreign markets for consumers to buy their prescription drugs and calls for limiting price increases on branded drugs and generics for drugs included in the Medicare program. It also calls for ending the tax deductions that pharmaceutical companies can take for the amount of money it spends on advertising its medications.

  1. M&A. Mergers and acquisitions (M&A) were not a huge factor in 2020, although there was quite a bit more venture capital funding than was initially expected, somewhat driven by an increased focus on biotech and pharma with the ongoing COVID-19 pandemic. Four big companies are cited as possible tasty takeover targets for 2021. They are:

• BioMarin Pharmaceutical. The company has a market cap of $15.4 billion and focuses on rare diseases, with six commercially approved drugs.

• uniQure. UniQure has a market cap of $2.1 billion. It is a strong potential player in the gene therapy space. Its lead candidate is AMT-061, an AAV5-based gene therapy being evaluated for severe and moderately severe hemophilia B in the Phase III HOPE-B study.

• Regenxbio. With a market cap of $1.6 billion, Regenxbio is also a gene therapy company. Its most advanced compound is RGX-314, in a Phase I/IIa trial for wet age-related macular degeneration. It also is developing three other gene therapies for rare neurological diseases.

• Deciphera Pharmaceuticals. Deciphera has a market cap of $3.2 billion. Its Qinlock was approved for advanced gastrointestinal stromal tumor (GIST) in May 2020 by the FDA. It is also being developed for GIST in other treatment settings and has several pipeline compounds for oncology.

  1. Venture Capital. PitchBook projected that venture capital (VC) activity for 2021 will exceed $20 billion. They think this is being fueled by growing capital commitments from VC investors hoping to enter the biopharma space, as well as recycling of profits and liquidity from this year’s initial public offering (IPO) market. So expect a lot of biotech startups and newer biotech companies to announce funding rounds.

“As we head into the new year, there are many variables on the table including the COVID-19 pandemic, a new administration in the U.S. with numerous policy proposals spanning taxes, immigration, trade and an array of other issues that directly affect both VC investors and companies,” said James Gelfer, senior strategist at PitchBook. “While macro uncertainty remains high, a light is beginning to appear at the end of the tunnel, and we see continued opportunity for innovation as investors, companies and regulators have seemingly embraced the new landscape and committed to increasing access to capital.”

One of the reasons they expect VC spending in biopharma to expand is that during 2020, particularly from March through about July, many pharma companies, if able, paused their clinical trials. Now that the vaccines are rolling out and expectations are that the pandemic will be brought under control by mid-2021 or earlier, more normal drug development activity will continue.

  1. BioMarin Pharmaceutical’s Roctavian for hemophilia B. In August 2020, the FDA issued a Complete Response Letter (CRL) for BioMarin’s Roctavian (valoctocognee roxaparvovec) for severe hemophilia A. The FDA recommended another two years of data from its ongoing 270-301 Phase III study to evaluate the durable effect using Annualized Bleeding Rate (ABR) as the primary endpoint. On the surface, that would suggest that the earliest the company could turn things around and get the drug onto market was in 2021.

But, the trial will have one-year results for all 134 participants early in 2021. Some of those 134 participants would have been followed for 18 to 24 months at that time, would if the data is supportive, could lead to an earlier turnaround for a resubmission.

  1. Bluebird bio’s ide-cel for relapsed and refractory multiple myeloma. In July 2020, Bristol Myers Squibb and bluebird bio resubmitted the BLA for idecabtagene vicleucel (ide-cel) for adults with relapsed and refractory multiple myeloma (RRMM). The resubmission included more details on the Chemistry, Manufacturing and Controls (CMC) module the FDA wanted after the original BLA submission in March 2020. The therapy was granted Breakthrough Therapy Designation by the FDA and Priority Medicines (PRIME) designation by the European Medicines Agency. Ide-cel is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T cell immunotherapy. The PDUFA date is March 27, 2021. If approved, it would be bluebird’s first commercial-stage drug.
  1. TG Therapeutics’ umbralisib for marginal zone lymphoma and follicular lymphoma. The FDA accepted TG Therapeutics’ New Drug Application (NDA) for umbralisib on August 13, 2020, with a PDUFA date of February 15, 2021for MZL and for FL in June 15, 2021. Umbralisib is a once-daily, oral, dual inhibitor of PI3K-delta and CK1-epsilon.

The MZL indication was accepted under Breakthrough Therapy Designation and Priority Review. The submissions were mostly based on data from the umbralisib monotherapy MZL and FL cohorts of the UNITY-NHL Phase IIb trial evaluating patients with r/r MZL or FL. Each cohort had met its primary endpoint of overall response rate (ORR), hitting the company’s target guidance of 40-50% ORR. If approved, either would be the first for the company.

AstraZeneca Vaccine Not Likely to Receive U.S. EUA Until April: Slaoui

 The United Kingdom authorized AstraZeneca’s COVID-19 vaccine on Wednesday, but it could be April at the earliest before the drug will likely be administered in the United States, Operation Warp Speed’s chief said.

During a call with reporters following the U.K. approval, Moncef Slaoui, head of the government’s effort to support the development of COVID-19 vaccine programs, pointed to questions about the amount of protection the vaccine could provide to the elderly, as well as conflicting efficacy reports of the vaccine developed by AstraZeneca and Oxford University. Those concerns have pushed back expected Emergency Use Authorization (EUA) of the AstraZeneca vaccine by two months.

This morning, Politico reported Slaoui predicted AstraZeneca’s vaccine will not be authorized until those questions can be answered. During a press call Wednesday, Slaoui said the known efficacy of the AstraZeneca vaccine is solid and appears effective against severe diseases. However, he went on to note that the vaccine’s efficacy is “effectively unknown” in elderly patient populations, which are among the most vulnerable to coronavirus infection. During clinical studies, AstraZeneca did not include enough of that patient population to provide enough evidence about the benefits that medication will have.

AstraZeneca’s COVID-19 vaccine candidate AZD1222 is a viral vector-based, weakened version of adenovirus containing the genetic material of SARS-CoV-2 spike protein. AstraZeneca’s efficacy is at 70.4%. During Phase III trials, one of the cohorts was administered one and a half doses, as opposed to two full doses. Vaccine efficacy in that cohort was up to 90%. The disparity is under investigation by the researchers. In interviews ahead of the U.K. authorization, AstraZeneca Chief Executive Officer Pascal Soriot expressed confidence the level of protection provided by his company’s vaccine will be close to that of the mRNA vaccines developed by Moderna and Pfizer and BioNTech, which demonstrated 94% and 95% efficacy, respectively.

While the 70% efficacy is well above the threshold set by the U.S. Food and Drug Administration for a COVID-19 vaccine, Slaoui, the former head of vaccine development at GlaxoSmithKline, suggested that U.S. regulators would not be satisfied by that conclusion, Politico reported.

“As far as the American people are concerned, I think it’s important to say one vaccine has 95 percent efficacy, another vaccine has X percent, whatever that number,” Slaoui said in reference to the efficacy ratings for the Moderna vaccines that have already received Emergency Use Authorization from the FDA. “We need a clear and concrete number more than a number that is accumulated by adding together different trials with different schedules and different materials.”

AstraZeneca indicates it expects to have capacity to manufacture up to 3 billion doses in 2021 on a rolling basis. Its vaccine could have a greater reach than the mRNA vaccines due to less stringent conditions required for storage and transport.

While AstraZeneca’s vaccine may not be used in the U.S. until spring, Johnson & Johnson could be in line to offer the third vaccine authorized in the United States. Earlier this month, the company said its Phase III ENSEMBLE study is fully enrolled with 45,000 participants. Interim data from the ENSEMBLE trial is currently anticipated to be available by the end of January. If the data indicate the vaccine is safe and effective, the company expects to seek EUA from the FDA in February.

Axsome’s Migraine Drug Provides Relief in Phase III Trial

 Axsome Therapeutics reported positive data from the long-term, open-label Phase III MOVEMENT trial of AXS-07 for the treatment of acute migraine.

The drug is a novel, oral, rapidly-absorbed drug with several methods of action. A new molecular entity, it utilizes the company’s Molecular Solubility Enhanced Inclusion Complex (MoSEIC) technology, which allows rapid absorption of meloxicam while maintaining a longer half-life in the blood. The drug is a combination of meloxicam and rizaptriptan. Meloxicam is a COX-2 preferential non-steroidal anti-inflammatory and rizaptriptan is a 5-HT1B/1D agonist.

The company expects to submit a New Drug Application (NDA) in the first quarter of 2021.

The MOVEMENT trial evaluated long-term safety of the drug for up to 12 months in patients with migraine attacks. It enrolled patients who had finished the previous pivotal trials, MOMENTUM and INTERCEPT. Patients in the trial were allowed to treat up to 10 migraine attacks per month up to a 12-month period, with a single dose of AXS-07 for each migraine.

A total of 706 patients were enrolled and it was finished when at least 300 patients had treated at least two migraines a month for six months, and about 100 patients had treated at least two migraines a month for 12 months. At the end of the study, 515 patients had reached at least six months, and 155 had reached at least 12 months. Over 21,000 migraine attacks were treated with the drug during the course of the trial.

“The results of the open-label, Phase III MOVEMENT trial confirm in a real-world setting the strong efficacy of AXS-07 observed in our previous controlled trials, and demonstrate a favorable long-term safety profile,” said Herriot Tabuteau, chief executive officer of Axsome.

He went on to say, “The rapid and substantial efficacy of AXS-07 now observed in three separate trials indicates that ASX-07 may provide unique benefits to patients with migraine and help address the current unmet need for more effective treatments. These data further support our planned NDA filing of AXS-07 in the acute treatment of migraine in the first quarter.”

In the MOVEMENT trial, dosing of AXS-07 caused rapid and “substantial relief” of migraine pain and the symptoms associated with it. These are often pulsating, severe and disabling head pain, nausea, sensitivity to light and to sound.

Within one hour after receiving AXS-07, 39% of participants achieved migraine pain relief. Two hours after receiving AXS-07, migraine pain relief was achieved by 68% of patients and pain freedom by 38%. Freedom from light and sound sensitivity and nausea was achieved by 47% of patients within two hours of receiving the drug.

The drug relieved migraine pain for 85% of patients in a durability evaluation, keeping them free from rescue medication use through 24 hours, and 83% free from rescue medication through 48 hours after a single administration. The study reported rates of sustained pain relief from two to 24 hours of 60% and two to 48 hours of 59%. Rates of sustained freedom from pain for two to 24 hours was 33% and from two to 48 hours was 32%.

The drug was well tolerated over long-term dosing with a 12-month safety profile consistent with those observed in the short-term trials. The most common adverse events were nausea, dizziness, and vomiting. During the year, only 1.6% of patients dropped out of the trial because of adverse events.

COVID-19 vaccine makers look back on 2020 for 2021 insights

 2020 was the year the biotech sector roared back to life. Led by COVID-19 vaccine developers, the iShares Nasdaq Biotechnology ETF (NASDAQ:IBB) returned 25.7% compared to 16.2% in the SPDR S&P 500 Trust ETF (NYSEARCA:SPY), signaling a remarkable turnaround from 2019 when SPY, with a 28.8% gain, outperformed the 25.0% rise in the IBB. 

With breakthrough technologies, the COVID-19 vaccine pioneers have dominated the year reaching record-breaking market capitalizations as the pandemic wreaked havoc across the globe. 

After languishing with a 25.4% gain in 2019, the vaccine maker Moderna (NASDAQ:MRNA) has climbed 434.1% in 2020 thanks to its COVID-19 injection, which recently won the FDA authorization for emergency use. The rival, BioNTech (NASDAQ:BNTX), is trailing with a 140.6% gain even though its partnership with Pfizer (NYSE:PFE) was the first to secure the emergency use signoff in the U.S. 

The frontrunners in the COVID-19 vaccine race are on track to generate more data readouts as they seek to file for full FDA clearance in 2021. The rival candidates are likely to join them, potentially capping their outsize gains. 

Jefferies has already downgraded Moderna, citing the record stock performance and upcoming Phase 3 data from the likes of AstraZeneca (NASDAQ:AZN), Johnson & Johnson (NYSE:JNJ), and Novavax (NASDAQ:NVAX). Against this backdrop, and amid concerns over a new COVID-19 strain detected in the U.K., both Moderna and BioNTech have shed 17.8% and 25.9%, respectively, in December though they have highlighted the efficacy of their shots against the new variant.

With over 3,000 times of increase in value, Novavax (NVAX) appears to have more than priced in its achievements against COVID-19 ahead of key late-stage data readouts scheduled for early 2021. Meanwhile, riding on the success of fellow mRNA-based vaccine developers, CureVac has risen 45.0% since its market debut in August, but the upcoming interim data reads in 2021 will justify its valuation.

A notable laggard in the vaccine race is AstraZeneca (AZN), with its COVID-19 shot developed in partnership with Oxford University recording an overall efficacy rate of only 70% in disease prevention per early data, well below the 95% reported by the approved mRNA-based vaccine developers. The vaccine already cleared in the home market is likely to undergo the U.S. regulatory review in early 2021, as the U.K.-based drug maker expects to submit data from a large American clinical trial by February for FDA approval.

Meanwhile, Johnson & Johnson (JNJ), with its late-stage trial fully enrolled, is likely to release interim data in late January for its single-dose vaccine candidate against COVID-19. An application for emergency authorization will follow in February, subject to safety and efficacy, shown in trial data. 

Reflecting the insignificant sales impact expected by Big Pharma from coronavirus vaccine franchises, AstraZeneca has remained flat throughout the year while JNJ has only eked out 7.9%, still better than the 6.2% decline of Pfizer.

With only three COVID-19 vaccines getting the regulatory approval so far, albeit, on an emergency basis, there is plenty to look forward to in 2021. Hope is that many other vaccine players will join them in 2021 as the World surely needs several of them to turn the tide against the raging pandemic where new COVID-19 variants have emerged to disrupt the containment efforts.