EU drug regulator to use UK data on adverse effects in assessment of Pfizer vaccine

 The European Union drug regulator will use data from Britain and other countries outside the EU on the safety of Pfizer-BioNTech’s COVID-19 vaccine before deciding whether to approve it, it said in a statement on Wednesday.

Britain’s medicine regulator has advised that people with a history of significant allergies do not get the Pfizer-BioNTech vaccine after two people reported adverse reactions on the first day of rollout on Wednesday.

Asked whether this new information could be used in the assessment of the vaccine in Europe, the European Medicines Agency said: “All available information on the quality, safety and efficacy of the vaccine will be taken into account. This will include safety data generated from the use of the vaccine outside the EU.”

https://www.reuters.com/article/us-health-coronavirus-britain-eu/eu-drug-regulator-to-use-uk-data-on-adverse-effects-in-assessment-of-pfizer-vaccine-idUSKBN28J2RY

J&J says cutting enrollment for COVID-19 vaccine trial by 20,000 as cases rise

 Johnson & Johnson said on Wednesday it has cut enrollment for its pivotal COVID-19 vaccine trial to 40,000 volunteers from its original plan for 60,000, as higher rates of COVID-19 infections amid a worsening pandemic should generate the data it needs with fewer study subjects.

The move could speed up the time frame for U.S. regulatory clearance, because they will need two months of follow-up safety data from 10,000 fewer people in order to meet U.S. Food and Drug Administration guidelines.

A top U.S. official said on a Wednesday press call that the lower target means the trial could be fully enrolled this week. J&J said it continues to expect an interim data readout in late January and could apply for U.S. emergency use authorization (EUA) in February.

“Given the high incidence of COVID-19 among the general population, we expect that approximately 40,000 participants will generate the data needed to determine the safety and efficacy of our investigational COVID-19 vaccine candidate,” J&J said in a statement.

The United States has reported an average and 205,661 new COVID-19 cases each day over the past week.

Meanwhile, Pfizer Inc could within days receive an EUA from the U.S. Food and Drug Administration for its vaccine, developed with Germany’s BioNTech SE, U.S. Health Secretary Alex Azar said on the call, adding that vaccinations could begin as soon as next week.

A panel of outside expert advisers to the FDA will meet on Thursday to review the Pfizer vaccine and decide whether to recommend that the agency grant the EUA. An FDA decision is expected soon after that.

Officials said they are preparing to distribute 2.9 million doses to more than 600 locations across the country once the vaccine is authorized. They are setting aside the remainder of their first 6.4 million-dose allotment to guarantee a second dose in the two-dose regimen for those who received a first shot, and to have a precautionary reserve.

Although the federal government is coordinating distribution efforts, states, territories, and five federal agencies will decide who should receive a vaccine first.

On Wednesday, the Department of Defense said it would receive about 44,000 doses of the initial nationwide supply and will prioritize vaccinating healthcare workers at military medical centers.

Moncef Slaoui, the chief adviser for U.S. efforts on coronavirus vaccines, said on Wednesday Americans with a history of severe allergic reactions may not be candidates for Pfizer’s vaccine, after two people with severe allergies had serious adverse reactions to the shot on the first day of vaccinations in the U.K. British health officials said both are recovering well.

Britain’s medicine regulator said it was changing its guidance to warn people with a history of significant allergies to vaccines, medicine and food to not get the vaccine.

Canadian health officials are making a similar recommendation after Canada approved the Pfizer/BioNTech vaccine on Wednesday.

https://www.reuters.com/article/us-health-coronavirus-vaccine/jj-says-cutting-enrollment-for-covid-19-vaccine-trial-by-20000-as-cases-rise-idUSKBN28J2S9

UK to refine allergy warning on Pfizer vaccine sparked by two adverse reactions

 Britain’s medicine regulator warned people with significant allergies not to get Pfizer-BioNTech’s COVID-19 vaccine after two people suffered adverse reactions, but was set to give more detailed guidance on Wednesday based on reviews of those cases.

Starting with the elderly and frontline workers, Britain began mass vaccinating its population on Tuesday, part of a global drive that poses one of the biggest logistical challenges in peacetime history.

National Health Service medical director Stephen Powis said the advice had been changed as a precaution after two NHS workers reported anaphylactoid reactions from the vaccine.

“Two people with a history of significant allergic reactions responded adversely yesterday,” Powis said. “Both are recovering well.”

The Medicines and Healthcare Products Regulatory Agency (MHRA) initially advised anyone with “a history of a significant allergic reaction to a vaccine, medicine or food” to avoid taking the vaccine.

However, by the end of Wednesday that guidance was set to be refined after discussions with experts on the nature of the reactions.

“We’re tweaking advice to make it very clear that if you’ve got a food allergy, you’re not more at risk,” Imperial College London’s Paul Turner, an expert in allergy and immunology who has been advising the MHRA on their revised guidance, told Reuters.

Pfizer and BioNTech said they were supporting the MHRA’s investigation.

Last week Britain’s MHRA became the first in the world to approve the vaccine, developed by Germany’s BioNTech and Pfizer, while the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) continue to assess the data.

A top U.S. official said on Wednesday that Americans with known severe allergic reactions may not be candidates for Pfizer’s COVID-19 vaccine until more was understood about what had happened.

Canada’s health ministry said it would look at the reported adverse reactions in Britain, but said adverse events were to be expected and would not necessarily change the risk/benefit of the shot, after the country approved the vaccine.

ALLERGIC REACTION

MHRA Chief Executive June Raine told lawmakers such allergic reactions had not been a feature of the Pfizer’s clinical trials.

Pfizer has said people with a history of severe adverse allergic reactions to vaccines or the candidate’s ingredients were excluded from their late stage trials, which is reflected in the MHRA’s emergency approval protocol.

However, the allergic reactions may have been caused by a component of Pfizer’s vaccine called polyethylene glycol, or PEG, which helps stabilise the shot and is not in other types of vaccines.

Imperial College London’s Turner said: “As we’ve had more information through, the initial concern that maybe it affects everyone with allergies is not true.”

“The ingredients like PEG which we think might be responsible for the reactions are not related to things which can cause food allergy. Likewise, people with a known allergy to just one medicine should not be at risk,” Turner told Reuters.

The EMA said in an email that all quality, safety and efficacy data would be taken into account in assessing the vaccine, including data generated outside the EU.

In the United States, the FDA released documents on Tuesday in preparation for an advisory committee meeting on Thursday, saying the Pfizer vaccine’s efficacy and safety data met its expectations for authorization.

The briefing documents said 0.63% of people in the vaccine group and 0.51% in the placebo group reported possible allergic reactions in trials, which Peter Openshaw, professor of experimental medicine at Imperial College London, said was a very small number.

“The fact that we know so soon about these two allergic reactions and that the regulator has acted on this to issue precautionary advice shows that this monitoring system is working well,” he said.

However, Gregory Poland, a virologist and vaccine researcher with the Mayo Clinic in Rochester, Minnesota, said that the MHRA and NHS had overreacted initially.

“I would not have broadened to the degree they did,” he said.

“It’s reasonable to let the world know about this, and to be aware of it in terms of people who have had reactions like this to vaccines. I think to say medicines, foods or any other allergies is past the boundary of science.”

https://www.reuters.com/article/health-coronavirus-britain-vaccine/uk-to-refine-allergy-warning-on-pfizer-vaccine-sparked-by-two-adverse-reactions-idUSKBN28J1D1

Novartis' Kisqali shows 5-year survival in pivotal breast cancer study

 

• Novartis (NVS +0.5%) has announced updated median overall survival results for Kisqali (ribociclib), from Phase 3 MONALEESA-7 trial evaluating Kisqali plus endocrine therapy as initial treatment compared to endocrine therapy alone, in HR+/HER2- metastatic breast cancer.
• According to data presented at the San Antonio Breast Cancer Symposium, Kisqali plus endocrine therapy helped pre- and perimenopausal women with HR+/HER2- disease live a median 58.7 months, compared with 48 months for endocrine therapy alone, translating to a 24% reduction in the risk of death for the Kisqali regimen.
• Similar median survival benefit of 58.7 months was observed with Kisqali plus an aromatase inhibitor subgroup vs. 47.7 months in the placebo plus aromatase inhibitor subgroup.
• Kisqali regimen also extended the time period before patients need follow-up chemotherapy. Patients on Kisqali combo lived a median 50.9 months before their first post-treatment chemo, while the time was 36.8 months for endocrine therapy alone.
• The company is also testing Kisqali in combination with the endocrine therapy letrozole in another Phase 3 trial, Monaleesa-2, in previously untreated patients; overall survival data is expected in 2H of 2021.
• https://seekingalpha.com/news/3643060-novartis-kisqali-shows-5-year-survival-in-pivotal-breast-cancer-study

Ultragenyx gene therapy Orphan Drug in U.S. for rare metabolic disorder

 

• The FDA designates Orphan Drug status to Ultragenyx Pharmaceutical's (NASDAQ:RARE) UX701 for the treatment of Wilson disease, a rare metabolic disease in which the body is unable to transport copper, thus accumulation of copper in the liver and other tissues. It is caused by mutations in the ATP7B gene, which results in deficient production of ATP7B, a protein that transports copper.
• UX701 is an investigational AAV type 9 gene therapy designed to deliver stable expression of the ATP7B gene. Currently in late preclinical development, and an investigational new drug application is expected to be filed with the FDA by the end of this year.
• https://seekingalpha.com/news/3643098-ultragenyxs-gene-therapy-orphan-drug-in-u-s-for-rare-metabolic-disorder

Pfizer/BioNTech COVID-19 vaccine docs hacked in Europe, companies say

 

• Pfizer (PFE -1.5%) and BioNTech (BNTX -3.4%) say documents related to their development of a COVID-19 jab have been “unlawfully accessed” in a cyber attack on Europe’s medicines regulator. No further details were provided.
• Both the company said no personal data of trial participants have been compromised and the European Medical Agency “has assured us that the cyber attack will have no impact on the timeline for its review.” They also added that “no BioNTech or Pfizer systems have been breached in connection with this incident".
• The Pfizer-BioNTech jab is among the top contenders in a global race to roll out a vaccine for COVID-19. Under emergency use nod, administration has begun in Britain.
• The vaccine is still being reviewed by the European Union, which is expected to complete by Dec. 29.
• https://seekingalpha.com/news/3643052-pfizer-biontech-covidminus-19-vaccine-docs-hacked-in-europe-companies-say

AstraZeneca COVID-19 vaccine data hint at single-dose efficacy, effect on asymptomatic cases

 Full data from late-phase trials of AstraZeneca’s COVID-19 vaccine have pointed to the potential for AZD1222 to work after a single dose and prevent asymptomatic cases but left key questions about the efficacy of the candidate unanswered.

The results, which were posted in The Lancet, reiterate the headline findings shared by AstraZeneca and its partners at the University of Oxford. In a pooled analysis of 11,636 participants enrolled in two separate clinical trials in the U.K. and Brazil, the efficacy of two doses of the vaccine was 70%. The paper adds the detail that protection against symptomatic disease after at least one standard dose was 64%. 

The two-dose efficacy figure masks divergent outcomes between subjects who began on a half dose and those that received two full doses. The efficacy on the 2,741-subject half-dose primer arm was 90%.

That discrepancy, which surprised the researchers running the trials, has been the subject of debate since AstraZeneca shared the top-line data. The Lancet paper provides background on how the U.K. trial came to give some subjects a half-dose primer and proffers potential explanations for the effect but leaves the core question of whether the regimen has 90% efficacy unanswered. 

The authors of the paper accept “there is a possibility that chance might play a part in such divergent results” but also see reason to think the findings may reflect actual differences between the efficacy of the two regimens. Those reasons rest on data on the numbers of asymptomatic cases. 

Participants in the U.K. phase 2/3 trial performed self-swabbing weekly to find asymptomatic cases. The process yielded positive results in the absence of reported symptoms in 69 subjects. The rate of asymptomatic infection in the half-dose cohort was 0.6%, versus 1% in the group that got two full doses. Divergences in the number of asymptomatic infections in the control arms contributed to the efficacy of the half-dose regimen coming in at 58.9%, versus 3.8% in the full-dose cohort. 

The authors of the paper cited the divergent effects on asymptomatic infection as evidence the half dose may be more efficacious. If that regimen actually prevents asymptomatic cases, it could enable AstraZeneca and its partners to vaccinate more people and reduce viral transmission, thereby giving protection to people who lack immunity against the virus. Yet, the efficacy remains unproven.

“The wide [confidence intervals] around our estimates show that further data are needed to confirm these preliminary findings,” the authors wrote. The researchers plan to confirm the findings through future analyses of data from the ongoing clinical trials.

No participants aged over 55 years received the half-dose primer. The 18- to 55-year-olds in the U.K. trial who did receive the half-dose shot were originally intended to only receive one dose. Data from early immunogenicity cohorts persuaded the researchers to amend the protocol. 

The rethink meant more than half of the low-dose group received their booster shot at least 12 weeks after the primer. Less than 1% received a second dose within eight weeks of the first shot. In the standard-dose cohort of the U.K. trial, less than 20% of participants got a second jab within six weeks of the first shot. In the Brazilian trial, more than 60% of people got two shots within six weeks of each other. 

Those discrepancies could affect the results if the lag between the prime and boost shots matters. The data downplay those concerns, with the results from U.K. participants who went eight weeks or more between doses mirroring the wider data set and efficacy across the two trials being numerically better in subjects with at least a six-week interval.  

Yet, the discrepancies provide ammunition for skeptics about the decision to pool results from two trials for the efficacy analysis and factor another two studies into the safety analysis. The authors of the Lancet paper defended the approach, stating that “despite minor differences across the studies, there is sufficient consistency to justify the proposal for pooled analysis of data, which will provide greater precision for both efficacy and safety outcomes than can be achieved in individual studies and provides a broader understanding of the use of the vaccine in different populations.” Analysts at SVB Leerink were downbeat about the data, though.

"The publication highlights a number of variances in the dosing regimens utilized in these trials that could make it difficult for the regulatory agencies to have confidence in the optimum dosing protocol for full approval without additional studies," the analysts wrote. 

The safety section of the paper addresses the case of transverse myelitis that put development on hold. The authors state the independent neurological committee found “the most likely diagnosis to be of an idiopathic, short segment, spinal cord demyelination.” There were two other cases of the condition across the full safety population, one in the control arm and one in a participant who took AZD1222 and was later found to have “pre-existing, but previously unrecognised, multiple sclerosis.” 

https://www.fiercebiotech.com/biotech/astrazeneca-covid-19-vaccine-data-hint-at-single-dose-efficacy-effect-asymptomatic-cases