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Wednesday, January 26, 2022

Cortexyme: Clinical Hold on Alzheimer's Investigational New Drug Application

 Cortexyme, Inc. (Nasdaq: CRTX), a clinical-stage biopharmaceutical company focused on Alzheimer’s and other degenerative diseases, today announced that the company received a letter from the U.S. Food and Drug Administration (FDA) on January 25, 2022 placing a full clinical hold on atuzaginstat’s (COR388) Investigational New Drug application (IND 134303). The company plans to provide additional updates pending continued engagement with FDA.

Cortexyme is immediately implementing a cost reduction program to rationalize operations and to allow continued support for planned clinical milestones, providing an expected cash runway through 2024. The company intends to prioritize development of its next generation gingipain inhibitor, COR588, in Alzheimer’s disease. COR588 is currently completing a Phase 1 SAD/MAD study and results are expected in the second quarter 2022. In addition, Cortexyme plans to explore strategic alternatives for its coronavirus program and non-Alzheimer’s indications for COR388. Cortexyme intends to provide a more detailed update on its pipeline and anticipated milestones for 2022 in the near future.

https://finance.yahoo.com/news/cortexyme-announces-clinical-hold-atuzaginstat-130000878.html

Early-stage US clinical holds spread

 It might be going too far to suggest that the recent spate of clinical holds is evidence of the FDA suddenly getting tough, but the fact that all of these concern very early-stage projects should give pause. The agency today put on hold a phase 1 X-linked adrenoleukodystrophy trial of Viking’s VK0214, after stymying no fewer than three IND applications, from Denali, Dyne and Yumanity, over the previous 10 days. And neither do these holds affect cutting-edge gene therapies, which have faced their own toxicity questions; the four assets in question comprise two small molecules, an antibody and a morpholino oligomer (two of these are using a TfR1-based transporter). At least Viking’s setback appears to be the result of a technicality; the FDA recently designated VL0214’s phase 1 trial a phase 2, something that requires a rodent genotoxicity study to be carried out first, Viking says. And it has not been all bad news of late: the FDA this month lifted two clinical holds, one on Spero’s nontuberculous mycobacterial disease project SPR720 and the other on Allogene’s entire pipeline. The Spero hold had been in place for 11 months, but Allogene’s took just three months to resolve.

Selected US clinical holds
Hold issuedHold announcedCompanyProjectStatus/detailCompany timeline
ND24 JanVikingVK0214Ph1 (now ph2) X-linked adrenoleukodystrophy trial on hold; rodent genotoxicity trial neededExpects to fulfil request Q2 2022
ND19 JanYumanityYTX-7739Preclinical (IND application on hold for multiple dosing in Parkinson's disease)None (no official hold letter yet)
14 Jan18 JanDyneDYNE-251Preclinical (IND application on hold for exon 51 skipper in Duchenne muscular dystrophy; more preclinical & clinical data requested)Expects to fulfil request Q2 2022
12 Jan13 JanDenaliDNL919Preclinical (IND application on hold for anti-Trem 2 MAb in Alzheimer's)None (no official hold letter yet)
Source: company announcements. ND=not disclosed.

https://www.evaluate.com/vantage/articles/news/trial-results-snippets/early-stage-us-clinical-holds-spread

Tuesday, January 25, 2022

Gilead: Partial Clinical Hold for Studies Evaluating Magrolimab Combo

 Enrolled Patients in These Studies May Continue Receiving Study Medicine --

-- Studies Outside of Combination with Azacitidine Unaffected --

Gilead Sciences Inc. (Nasdaq: GILD) today announced that the U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on studies evaluating the combination of magrolimab plus azacitidine due to an apparent imbalance in investigator-reported suspected unexpected serious adverse reactions (SUSARs) between study arms. While no clear trend in the adverse reactions or new safety signal has been identified by Gilead at this time, the partial clinical hold is being implemented by Gilead across all ongoing magrolimab and azacitidine combination studies worldwide in the best interests of patients as additional data is gathered and analyzed to address the concerns raised by FDA.

During the partial clinical hold, screening and enrollment of new study participants will be paused in any study investigating the combination of magrolimab with azacitidine. Patients already enrolled in these clinical studies may continue to receive magrolimab and azacitidine, or placebo, and continue to be closely monitored according to the current study protocol. Gilead is currently notifying clinical investigators and global regulatory authorities about the partial clinical hold. Other magrolimab studies, or cohorts, that are not studying the combination of magrolimab plus azacitidine, will continue without any impact by the partial clinical hold.

"The safety and well-being of people enrolled in our studies is our top priority. We will share more information with the medical and patient community as soon as we can,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. “Considering the high unmet need for new medicines in myelodysplastic syndrome and acute myeloid leukemia, we will work closely with regulatory authorities worldwide to continue the magrolimab development program appropriately. We remain confident in the potential of magrolimab across a broad range of tumors, including the other, ongoing magrolimab studies. We are grateful to those participating in our studies, their families, and the investigators for their continued contributions to the clinical program for magrolimab.”

Gilead is working with regulatory authorities to determine next steps to release the partial clinical hold for new patient enrollment for the affected studies.

https://www.gilead.com/news-and-press/press-room/press-releases/2022/1/gilead-announces-partial-clinical-hold-for-studies-evaluating-magrolimab-in-combination-with-azacitidine

Lonza's full-year core EBITDA up 20.7% on vaccine demand

 FY core EBITDA 1.67 bln francs, in line with market view

* Guides for low to mid-teens forex adj sales growth

Swiss drug contract manufacturer Lonza said core earnings gained 20.7% in 2021, shored up by demand for the substances it supplies for new mRNA COVID-19 vaccines.

Full-year core earnings before interest, tax, depreciation and amortization (EBITDA) rose to 1.67 billion Swiss francs ($1.82 billion), up from 1.38 billion a year earlier, it said in a statement on Wednesday. That was broadly in line with an analyst consensus posted on its website.

The company, which is a key supplier of vaccine maker Moderna, is stepping up investments as it banks on long-term growth in the biopharmaceuticals sector well beyond the pandemic.

For this year, Lonza predicted "low to mid-teens" sales growth, when excluding currency swings, as well as core EBITDA margin improvement from 30.8% in 2021.

https://www.marketscreener.com/quote/stock/LONZA-GROUP-AG-2956013/news/Lonza-s-full-year-core-EBITDA-up-20-7-on-vaccine-demand-37642147/

Mind Medicine Gets FDA Clearance for IND Application for Anxiety Treatment

 Mind Medicine Inc. said the U.S. Food and Drug Administration has cleared its investigational new-drug application, allowing the company's Phase 2b dose-optimization trial of MM-120 for the treatment of generalized anxiety disorder to proceed.

The biopharmaceutical company said the previously announced clinical hold on the IND was lifted following its rapid responses for additional information related to the participant monitoring protocol in the coming study.

Mind Medicine said it is working with study investigators and clinical trial sites to prepare for participant enrollment, which is expected to start in early 2022.

https://www.marketscreener.com/quote/stock/MIND-MEDICINE-MINDMED-I-120797784/news/Mind-Medicine-Gets-FDA-Clearance-for-IND-Application-for-Anxiety-Treatment-37634434/

NY Mask Mandate Back, But Still In Limbo: What Schools And Businesses Should Know

 A legal seesaw threw Gov. Kathy Hochul's mask mandate into question this week, creating chaos at schools and businesses, as counties decided whether or not to keep abiding by the rule.

On Monday, a New York State Supreme Court judge ruled that Hochul’s mask mandate for indoor public spaces was invalid because she overstepped her authority when she put it in place in mid-December without going through the state legislature.

The state attorney general requested a stay on Tuesday to keep the mask mandate in place while the case makes its way through the appeals process. Following a hearing Tuesday afternoon, a judge ruled in favor of keeping the mandate in place for now, but it could still get thrown out again.

With the legal battle ongoing, there’s understandably some confusion about the current status of the state mask mandate and what it means for teachers, students, retail workers and others who might be affected. Some school districts such as those on Long Island immediately dropped their mandates, which a legal expert said might be a violation. Meanwhile, New York City schools kept their rules in place. And even if the mandate remains in effect, what happens when it is due to expire next month?

WNYC/Gothamist reached out to state and local authorities and groups representing different sectors to gain some clarity on the situation.

Here’s what we know so far.

How New York Got Here

Hochul initially announced the mask mandate on December 10th, saying it was a response to rising COVID-19 cases in New York. She said that all businesses and venues that didn’t have a vaccine requirement in place must mandate staff and patrons to wear masks. She added that state masking requirements remained in effect for schools, public transit and other settings. The rule was officially issued the following day via an order from State Health Commissioner Mary Bassett. It was set to expire on January 15th, but was later extended until February 1st.

The key here is Bassett, more than Hochul. According to Judge Thomas Rademaker at the State Supreme Court in Nassau County, the state legislature would have to pass a law to require masking in public spaces in order for the mandate to be legal. Rademaker’s opinion said Bassett did not have the authority to issue a public health rule affecting all businesses statewide. And he said Hochul could not issue such a mandate on her own.

That’s partially because the state legislature curbed former Gov. Andrew Cuomo’s pandemic powers in March 2021, after he issued several executive orders related to masks and other safety precautions during the pandemic. He had used emergency powers granted by the state legislature early in the crisis, allowing him to make decisions unilaterally and overrule county and city leaders.

“To be clear, this court does not intend this decision in any way to question or otherwise opine on the efficacy, need, or requirement of masks as a means or tool in dealing with the COVID-19 virus,” Judge Rademaker wrote. Rather, he said he was only ruling on whether the mandate was properly enacted and could be enforced.

This ruling is also similar to what happened when the State Supreme Court overruled Mayor Michael Bloomberg’s ban on soda and sugary drinks in 2013, said Roderick Hills, a law professor at the NYU School of Law.

“Just as that earlier opinion said that the Board of Health in New York [City] did not have authority to limit the size of containers for soft drinks, so too this opinion says there's nothing from the state legislature authorizing Bassett to force people to wear face masks,” said Hills, who specializes in governmental separations of powers.

 The public health law does not give the state commissioner any broad regulatory powers. 

 Roderick Hills, NYU School of Law

During a hearing Tuesday afternoon at a State Appellate Court to determine whether the mandate will remain in place while it’s being contested, a lawyer for the state argued that the health department regularly issues rules to promote public health and that voiding the mandate would cause irreparable harm. But Hills said he didn’t think Bassett had the authority to require masking in private businesses.

“The public health law does not give the state commissioner any broad regulatory powers,” he said. “So, if you don't have emergency powers, you're kind of left with a gun containing no bullets.”

At a press conference Tuesday afternoon, Hochul pledged to keep fighting for the current mandate in court: "We disagree 100% with the conclusion of the judge who, in his opinion, thought that the Department of Health did not have the authority to protect public health. A judge in Albany — same fact pattern — came up with the opposite conclusion. So we believe it will be settled very shortly.”

Hochul said she was bolstered by the appellate court ruling Tuesday afternoon: “We will not stop fighting to protect New Yorkers, and we are confident we will continue to prevail."

“Typically, these decisions about temporary restraining orders or stays require both a look at how harmful it would be if the judge got it wrong — and also how wrong the judge was because the law in fact was on the state's side,” he said, adding that Judge Rademaker’s legal rationale seems to be strong. “As for the harm that will be done if he got it wrong, obviously, that could be significant.”

Does Your School District Still Need To Follow Mask Mandates?

The short is answer is yes, despite the dueling opinions and war of words playing out in the news between school district leaders and state officials.

Some school districts in New York state have told parents and students that masking is optional while the governor’s rule is under review by the courts. Nassau County Executive Bruce Blakeman told the governor to “stand down” on the mask requirement and “bend to the will of the people.”

But the New York State Education Department filed an emergency order requiring masks in schools in August. The Department said in a statement Tuesday, “While these legal steps occur, it is NYSED’s position that schools should continue to follow the mask rule.”

According to Hills, the State Education Department likely can require masking in schools statewide regardless of whether the governor’s mandate is ultimately defeated or expires. “The department of education has far more authority over schools than the state health commissioner has over you and me,” Hills said.

Andy Pallotta, president of the New York State United Teachers union, said in a statement Tuesday that mask mandates in schools should remain in place as long as they are recommended by public health experts but that “we’re looking to state health officials to set a clear off-ramp for when mask requirements in schools can be relaxed so students, families and educators have some certainty that there is light at the end of this long tunnel.”

Likewise, Rademaker’s ruling has no impact on the mask requirement put in place by New York City’s public schools because its long-standing mandate draws its authority from the state Department of Education. A spokesperson for the city’s education department said its mandate would remain in place regardless of what happens with the state mandate.

Amidst the confusion, Hochul urged parents, teachers and school districts to keep following the state education department’s mask mandate to curb the spread of the highly contagious omicron variant.

“I'm encouraging parents and students to continue doing what they're doing because the last thing I want to see is a different trend because people gave up on masks," she said.

Restaurants, Bars and Other Businesses Face The Most Confusion

In New York City, the Key to NYC executive order requires bars, restaurants, gyms and entertainment venues to check the vaccination status of employees and customers.

Since the governor’s mask mandate only applies to businesses without a vaccine requirement, the outcome of this case won’t have a major impact on the protocols for these spaces, noted Andrew Rigie, executive director of the New York City Hospitality Alliance. Still, Rigie said, “all the ever-changing COVID requirements have created lots of confusion for small business owners.”

But New York City does not have a mask requirement in place for any business, just a recommendation. So, if the governor’s mandate is ultimately invalidated, that would mean supermarkets, bodegas, clothing stores and other businesses can still set their own policies around masking, but they won’t have a state mandate to back them up.

In other parts of the state, any business without vaccine requirements has more riding on the decision — and the coming days could be very confusing. Here’s a breakdown, step by step.

  1. For now, all businesses outside of New York City still have to require their patrons to be masked if they’re unvaccinated following Tuesday’s appeal, which granted a stay to Monday’s decision. In other words, the state’s vaccine-or-mask requirement is back in effect.
  2. This decision will likely be appealed again and go before the New York State Court of Appeals. Its ruling would be final.

“There's no federal issue here, so it can't go to the U.S. Supreme court…This is purely a matter of state law,” Hills said. “The only thing that can happen is that the state legislature in Albany, actually enact a statute authorizing the health commissioner to do what she did.”

Some businesses have safety precautions – including mask protocols – that they have agreed to put in place as part of collective bargaining agreements, said Chelsea Connor, a spokesperson for the Retail, Wholesale and Department Store Union. But she noted that the union only represents about 45,000 retail workers in New York state.

Kathryn Wylde, president and CEO of the Partnership for NYC, an organization representing businesses, said she thought that most local employers support a vaccine-or-mask policy in the workplace.

https://gothamist.com/news/nys-mask-mandate-is-back-but-still-in-limbo-heres-what-schools-and-businesses-should-know

Omicron Survives Longer on Plastic, Skin Than Other COVID Variants

 Japanese researchers say the Omicron variant survives longer on plastic and skin than other COVID-19 variants, one possible explanation for why Omicron has spread so rapidly around the world.

In a lab experiment, samples of different variants were applied to pieces of plastic and human skin collected from autopsies, researchers from Kyoto Prefectural University of Medicine wrote in bioRxiv. A variant “survived” until it could no longer be detected on the surface.

“This study showed that the Omicron variant also has the highest environmental stability among VOCs (variants of concern), which suggests that this high stability might also be one of the factors that have allowed the Omicron variant to replace the Delta variant and spread rapidly,” the researchers wrote.

On plastic, the Omicron variant samples survived an average of 193.5 hours, a little more than 8 days. By comparison, the other survival times on plastic were 56 hours for the original COVID strain, 191.3 hours for Alpha, 156.6 hours for Beta, 59.3 hours for Gamma, and 114 hours for Delta.

On skin samples, the Omicron samples survived an average of 21.1 hours. The other variants had these average survival times on skin: 8.6 hours for the original version, 19.6 hours for Alpha, 19.1 hours for Beta, 11 hours for Gamma, and 16.8 hours for Delta.

The study found that the variants had more resistance to ethanol than the original strain of COVID. That said, all COVID samples were inactivated after being exposed to alcohol-based hand sanitizers for 15 seconds.

"Therefore, it is highly recommended that current infection control (hand hygiene) practices use disinfectants ... as proposed by the World Health Organization," the researchers said.

The study has not been peer-reviewed.

https://www.webmd.com/lung/news/20220125/omicron-survives-longer-plastic-skin-than-other-covid-variants