South African variant termed unlikely to 'completely negate' COVID vaccines

 A variant of the coronavirus first detected in South Africa is unlikely to completely negate the immunising effects of vaccines, a researcher studying it told Reuters.

British scientists expressed concern on Monday that COVID-19 vaccines may not be able to protect against the variant identified by South African scientists and which has spread internationally.

Richard Lessells, an infectious disease expert at the KwaZulu-Natal Research Innovation and Sequencing Platform, which played a central role in identifying the variant known as 501Y.V2, said his understanding was that the comments were not based on any new data but on shared information.

“They are voicing the same concerns that we articulated when we first released this information, that the pattern of mutations did give us concern,” Lessells said on Tuesday.

South African researchers are studying the effects of mutations in the variant, including whether natural immunity from exposure to older versions of the virus provides protection against reinfection by the new variant.

Preliminary results from those studies may be ready by the end of this week, Lessells said.

Scientists have identified more than 20 mutations in the 501Y.V2 variant, including several in the spike protein the virus uses to infect human cells.

One of these is at a site that is believed to be important for neutralising antibodies and is not found in another coronavirus variant discovered in Britain, Lessells said.

“Why we’ve been a bit cautious about flagging out the concern about the (effectiveness of) vaccines is that for many of the vaccines they are thought to induce quite a broad immune response,” he said.

That broad response could target different parts of the spike protein, not just one, he added.

“That’s why we think that although these mutations may have some effect, they are very unlikely to completely negate the effect of the vaccines,” Lessells said.

South Africa’s health ministry acknowledged questions from Reuters but did not give an immediate response. The country has recorded more than 1.1 million COVID-19 cases and in excess of 30,000 deaths, the most on the African continent.

Public Health England has said there is no evidence to suggest COVID-19 vaccines would not protect against mutated coronavirus variants.

BioNTech chief executive Ugur Sahin said in an interview last week that his company’s vaccine, which uses messenger RNA to instruct the human immune system to fight the virus, should be able to protect against the British variant.

https://www.reuters.com/article/us-health-coronavirus-safrica-vaccines/south-african-variant-unlikely-to-completely-negate-covid-vaccines-scientist-says-idUSKBN29A27R

89bio Provides Business Outlook for 2021

 -Phase 2b NASH trial as part of a potential Phase 2b/3 program expected to initiate in 1H21-

-Topline data from recently initiated NASH paired-biopsy, open-label histology cohort expected by YE21-

-Topline data from BIO89-100’s Phase 2 SHTG trial expected in 2H21-

http://www.globenewswire.com/news-release/2021/01/05/2153441/0/en/89bio-Provides-Business-Outlook-for-2021.html

BioXcel scores win with reformulated Pfizer sedative in Alzheimer's symptom

Less than six months after reporting positive Phase III results for its lead program in treating agitation related to schizophrenia and bipolar disorder, small AI biotech BioXcel followed up Tuesday with top-line data in an early stage trial for agitation in dementia and Alzheimer’s disease.

The experimental drug, known as BXCL501, met its primary and secondary endpoints in the higher evaluable dose of a 54-patient Phase Ib/II trial, BioXcel announced, inducing a statistically significant calming effect compared to placebo with no severe or serious side effects. With the data in hand, BioXcel plans to meet with the FDA sometime in the first half of 2021 before launching a late-stage study sometime afterwards.

BioXcel $BTAI shares ticked up by as much as 10% in pre-market trading Tuesday, but after the opening bell were down about 7%.

BXCL501 is a reformulation of Pfizer’s 21-year-old sedation drug Precedex. BioXcel created a dissolving film-based, sublingual version of the drug — think Listerine strips, but placed under the tongue — that patients administered themselves. It essentially produces a calming effect without knocking a patient out and activates the alpha-2 receptor, the pathway through which norepinephrine, among other neuro-chemicals, travels.

Tuesday’s data come from a double-blinded and randomized study conducted entirely within assisted living facilities. Patients in the drug cohorts received either a 30 μg, 60 μg or 90 μg dose, though BioXcel did not measure efficacy or safety in the 90 μg arm due to higher exposure levels. Sixteen patients received the 30-μg dose, 20 took the 60-μg dose, four began the 90-μg dose level and 14 were randomized to the placebo group.

It’s the 60 μg level where BXCL501 differentiated itself from placebo at a significant level. The program hit on all three scales used to measure change in agitation from baseline, the PEC, PAS, and Mod-CMAI. For the PEC, the p-value was p=0.0011, while the other two p-values registered at p<0.0001.

The candidate also showed a rapid onset, BioXcel said, hitting statistical significance compared with placebo in the PEC and PAS just one hour after patients took the film strips, with the company noting it didn’t measure Mod-CMAI after this time period. Calming effects at this dosing level remained at statistically significant levels through eight hours.

BXCL501’s 30-μg dose did not hit statistical significance in any of the three scales, clocking in at p=0.0813 for PEC, p=0.0961 for PAS and p=0.0591 in the Mod-CMAI.

The most common side effect was somnolence, or drowsiness. Half of the 16 patients in the 30-μg cohort self-reported mild drowsiness, while 11 of 20 individuals in the 60-μg cohort did so. There was one case of moderate drowsiness in the 60-μg group as well.

In addition, there were two cases of hypotension in the 60-μg cohort, one mild and one moderate, as well as one case of mild dizziness.

Jefferies analyst Chris Howerton took a positive view of the data, writing that the 60-μg dose appears to “check all the boxes.” The safety at this dose level looked “clean,” though Howerton noted because Precedex is known to be more potent in elderly patients, he wouldn’t be surprised if BioXcel also looked at a 45-μg dose in their pivotal trial.

The issue of a 45-μg dose also came up in a conference call BioXcel held Tuesday morning with investors. CEO Vimal Mehta said that although BioXcel will likely prioritize 60 μg for the Phase III given Tuesday’s top-line results, they aren’t ruling out also testing 45 μg.

Mehta also said on the call that he doesn’t anticipate much disruption in Phase III enrollment related to the ongoing Covid-19 pandemic.

BioXcel is one in a slate of biotechs that has raised millions in recent years on the promise of using artificial intelligence to speed the drug development process. The company filed for a $69 million IPO in 2018 less than a year after being founded, and has aimed to use its tech to find compounds validated to some degree by other companies and repurpose them.

Back in July, BioXcel reported that in two nearly 400-person Phase III trials for bipolar disorder and schizophrenia, the lead drug effectively calmed patients’ agitation.

https://endpts.com/bioxcel-scores-another-win-with-reformulated-pfizer-sedative-this-time-in-an-alzheimers-symptom/ 

MedTech Stryker acquires digital knee replacement developer OrthoSensor

 Stryker has acquired OrthoSensor, a former Fierce 15 winner focused on applying digital technologies and big data to total joint replacements.

Using a set of disposable, implantable sensors and a cloud-based data collection system, OrthoSensor aims to help surgeons quantify and standardize their knee arthroplasty procedures instead of having to rely on more subjective measures.

By providing real-time data on the load and compression forces placed on the joint during an operation, surgeons can make more informed decisions on balancing the knee’s soft tissue and adjusting the implant’s placement.

“Smart devices and implants will play a big role in orthopaedics and we are excited for OrthoSensor to join Stryker as we continue to innovate and advance smart sensor technologies, including intraoperative sensors, wearables and smart implants across our joint replacement business,” said Spencer Stiles, president of Stryker’s orthopedic and spine group.

“Patient recovery will become more active as real-time measurement on key performance insights drive improved outcomes and patient satisfaction,” Stiles said.

The Florida-based company has previously maintained partnerships with Stryker as well as its orthopedics competitors Zimmer Biomet and Smith & Nephew. 

Going forward, Stryker hopes to see OrthoSensor’s portfolio complement its surgical robotics workflow by feeding additional, intraoperative data back into the system alongside postoperative remote patient monitors, wearables and analytics. The deal was made for an undisclosed sum.

https://www.fiercebiotech.com/medtech/stryker-acquires-digital-knee-replacement-developer-orthosensor

FDA says half-dosing Moderna COVID-19 vaccine ‘risks public health,’ lacks data

 Following reports that the U.S. Food and Drug Administration was in talks with Moderna and Operation Warp Speed officials to consider halving vaccines’ dose volume to speed inoculations and extend supply, the federal watchdog late Monday dismissed the approach, calling it a "significant public health risk."

In a joint statement, FDA Commissioner Dr. Stephen Hahn and Dr. Peter Marks, head of the FDA's Center for Biologics Evaluation and Research, advised the public to adhere to the authorized dosing and vaccination schedules: two-doses 21 days apart for Pfizer/BioNTech COVID-19 vaccine and two-doses 28 days apart for the Moderna COVID-19 vaccine.

"At this time, suggesting changes to the FDA-authorized dosing or schedules of these vaccines is premature and not rooted solidly in the available evidence," reads the statement. "Without appropriate data supporting such changes in vaccine administration, we run a significant risk of placing public health at risk, undermining the historic vaccination efforts to protect the population from COVID-19."

The news follows comments from Dr. Moncef Slaoui, the chief operating officer for Operation Warp Speed, who told CBS’ Margaret Brennan that halving the dose volume in Moderna vaccines administered to those aged 18 to 55 translates to an "identical immune response" to the full, 100-microgram dose. 

This plan would inoculate twice the amount of people, Slaoui said, calling it a "more responsible approach based on facts and data."

Slaoui did not, however, endorse spacing vaccinations apart further than the authorized schedule.

"I think it’s not reasonable, when vaccines have been developed with two doses given 21 days apart, or 28 days apart and where we have the data on their safety and their efficacy," Slaoui said. "We have no data on one dose if we leave people a month, two months, three months with maybe incomplete immunity, waning immunity, maybe even the wrong kind of immune response induced that is then corrected by a second dose."

The U.S. FDA’s stance directly conflicts with an approach in the U.K., with officials backing a decision to space out vaccine doses 12 weeks apart, in a bid to "save lives" and distribute first doses wider across the population. Though the U.K. has yet to authorize Moderna’s vaccine, it has rolled out jabs for Pfizer and AstraZeneca, the former of which said its vaccine should be administered within the 21-day specified period. Though AstraZeneca previously said a dosing regimen spaced up to 12 weeks apart was safe and effective in clinical trials.

"You can’t just give one shot the way the United Kingdom is doing and hope that the second shot magically appears," Dr. Marc Siegel, Fox News medical contributor, told "FOX & Friends" co-hosts Tuesday.

The FDA noted "common misinterpretations" of the drug sponsors’ data regarding the first dose. While the vast majority of participants in Pfizer's and Moderna’s clinical trials received two doses about three to four weeks apart, 98% and 92%, respectively, the participants who deviated from the timeline were only followed briefly, not allowing the FDA to form "definitive" conclusions about level of protection, and length of protection, afforded by single-dose shots.

Despite Slaoui’s comments that halving the Moderna dose would result in an "identical immune response" in individuals aged 18 to 55, the FDA said altering the dosage from that studied in clinical trials is "concerning," citing "some indication" that the immune response is linked to duration of protection.

"We know that some of these discussions about changing the dosing schedule or dose are based on a belief that changing the dose or dosing schedule can help get more vaccine to the public faster," the statement continues. "However, making such changes that are not supported by adequate scientific evidence may ultimately be counterproductive to public health."

Moderna got FDA emergency authorization for its coronavirus vaccine on Dec. 18, one week after a vaccine developed by Pfizer and BioNTech received the same designation. Both vaccines are over 90% effective at preventing COVID-19 disease. At the time, an independent advisory panel to the FDA found that the Moderna vaccine reduced the risk of confirmed COVID-19 – including severe cases – occurring at least 14 days after the second dose.

Of note, the panel noted that the Moderna clinical trial didn't have a single-dose arm for comparison.

"The efficacy observed after dose 1 and before dose 2, from a post-hoc analysis, cannot support a conclusion on the efficacy of a single dose of the vaccine, because the numbers of participants and time of observation are limited," reads panel documents posted ahead of the December review.

https://www.foxnews.com/health/fda-half-dosing-moderna-coronavirus-vaccine-risks

Cerecor Has Successful Phase 2 Data on Antibody in Patients Hospitalized with COVID-19 ARDS

 

• COVID-19 ARDS patients treated with a single dose of the anti-LIGHT monoclonal antibody CERC-002 demonstrated robust improvement in the primary endpoint (proportion of patients alive and free of respiratory failure over the 28-day study period) compared to placebo (n=62, odds ratio [OR] = 2.62, p=0.059)
• A prespecified subgroup analysis of patients 60 years of age showed that CERC-002 treatment led to a greater than 3-fold increase in likelihood of avoiding respiratory failure and death compared to placebo (n=33, OR = 3.38, p=0.054)
• 28-day mortality was reduced by approximately 50% in patients treated with CERC-002 (3 patients) vs. placebo (6 patients). There were a total of 4 COVID-19 related deaths in patients on CERC-002 vs. 9 on placebo as of December 2020. These data will be updated and analyzed at the 60-day timepoint
• Importantly, CERC-002 showed activity on top of corticosteroids in COVID-19 ARDS (>90% of patients in the trial received corticosteroids and >60% received remdesivir)
• CERC-002 dramatically and rapidly reduced serum free-LIGHT levels
• CERC-002 was well tolerated with no drug related SAEs and no clinically meaningful differences in immunosuppression or other SAEs between CERC-002 and placebo
• The company intends to meet with the FDA and believes that these data support the initiation of a registration trial and filing for Breakthrough Therapy Designation. Additionally, the company is continuing its program in severe pediatric-onset Crohn’s disease and is exploring the applicability of CERC-002 in non-COVID-19 ARDS
• http://www.globenewswire.com/news-release/2021/01/05/2153315/0/en/Cerecor-Announces-Successful-Proof-of-Concept-Data-for-CERC-002-a-Unique-LIGHT-Neutralizing-Antibody-in-Patients-Hospitalized-with-COVID-19-ARDS.html

China's CNBG has supplied 3 million COVID-19 vaccine doses to UAE

 United Arab Emirates (UAE) has received a total of three million COVID-19 vaccine doses from China National Biotec Group (CNBG), the company said on Tuesday.

CNBG has moved into late-stage clinical trials two COVID-19 vaccine candidates respectively developed by its units in Beijing and Wuhan city. The Beijing unit’s shot obtained a green light last week for general public use in China.

CNBG is a subsidiary of state-backed China National Pharmaceutical Group (Sinopharm).

“According to preliminary feedback from UAE, emergency use shows that Sinopharm CNBG’s COVID-19 vaccine is safe in large-scale use and has significantly reduced the disease in vaccinated people,” CNBG said in an article published on Chinese social media WeChat, without specifying which candidate it referred to.

The firm didn’t break down the numbers of doses for each candidate in its supply to UAE. It’s not immediately clear how many of these doses were used in clinical trials and how many in real-life use.

Pakistan said last week it would purchase 1.2 million doses of the vaccine developed by CNBG’s Beijing unit.

https://www.reuters.com/article/us-health-coronavirus-vaccine-cnbg/chinas-cnbg-has-supplied-3-million-covid-19-vaccine-doses-to-uae-idUSKBN29A14H