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Cortexyme Crashes as Key Alzheimer’s Asset Hit with Clinical Hold

South San Francisco-based Cortexyme Inc. received a letter from the U.S. Food and Drug Administration on January 25 placing a full clinical hold on the Investigational New Drug application for the company’s lead clinical asset atuzaginstat, which is…

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Cortexyme Crashes as Key Alzheimer’s Asset Hit with Clinical Hold

South San Francisco-based Cortexyme, Inc., received a setback in its latest research efforts. The company announced that it received a letter from the U.S. Food and Drug Administration on January 25, placing a full clinical hold on the Investigational New Drug application for lead clinical asset atuzaginstat, which is in development for the treatment of Alzheimer’s disease.

Cortexyme said it plans to provide additional updates pending further talks with the FDA.

Meantime, on the stock market, shares of Cortexyme dropped sharply in premarket trading Wednesday following the announcement. Company shares, which closed Tuesday at $9.06, fell to $6.47, a drop of 29.6%.

The company’s lead program targets an infectious pathogen called P. gingivalis found in the brains of Alzheimer’s patients, and other organs, which is tied to degeneration and inflammation.

Following the FDA’s action, Cortexyme is immediately cutting expenses to ensure cash flow through 2024. The company intends to rationalize operations, which will enable continued support for planned clinical milestones. A top priority will be development of its next-generation gingipain inhibitor, COR588, also being investigated in Alzheimer’s disease. The company is completing a Phase 1 study and expects results in the second quarter of 2022.

Source: BioSpace

The company also plans to look into strategic alternatives for its coronavirus program and assess possibilities for atuzaginstat outside of the Alzheimer’s indication. In its statement, Cortexyme let investors know that a more detailed update on its project pipeline and expected milestones for 2022 would be forthcoming.

In November, Cortexyme presented data from its Phase II/III GAIN trial at the 14th Clinical Trials on Alzheimer’s Disease Conference (CTAD). The 643-participant study was the first large trial to test the efficacy of an oral small-molecule targeting P. gingivalis in mild to moderate Alzheimer’s patients. It failed to reach statistical significance in its co-primary cognitive and functional endpoints at the end of treatment across the overall trial population. However, the data did show that treatment with atuzaginstat slowed cognitive decline compared to placebo in participants with Alzheimer’s disease and P. gingivalis infection.

“Our ability to identify the right population in historically hard to treat mild to moderate Alzheimer’s patients, along with finding an efficacious dose with a differentiated safety profile, is important progress toward a breakthrough treatment for Alzheimer’s disease,” said Cortexyme Chief Medical Officer Michael Detke, M.D., Ph.D. at the time.

Marwan Sabbagh, M.D., FAAN, lead investigator of the GAIN Trial and professor of neurology at the Barrow Neurological Institute, added, “The GAIN Trial achieved several significant advancements for the Alzheimer’s field, first by clinically confirming that P. gingivalis is a key upstream driver of disease progression. Further, the data demonstrated a compelling risk-benefit profile with a clinically significant treatment response in an easily identifiable population of patients.”

He further stated, “When coupled with the convenience of oral dosing, atuzaginstat offers the potential to fill a huge gap in the underserved mild to moderate Alzheimer’s population in as many as half those patients.”

In August 2021, Cortexyme presented data from the same study at the Annual Biomarkers for Alzheimer’s Disease Summit. The data showed evidence of P. gingivalis infection of the central nervous system in trial participants. P. gingivalis is the same bacterial strain that is responsible for chronic periodontitis.

Cortexyme CEO and Co-Founder Casey Lynch said at the time, “Today marks a major milestone toward a comprehensive understanding of Alzheimer’s and slowing of disease progression. The evidence from the GAIN trial advances our ability to identify the right patients, impact an upstream target and improve patient outcomes.”

BioSpace source:

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Spread & Containment

Moderna’s HIV vaccine prepped for trials in Africa

Moderna has joined forces with non-profit organisation IAVI on a third phase 1 trial of its candidate HIV
The post Moderna’s HIV vaccine prepped for…

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Moderna has joined forces with non-profit organisation IAVI on a third phase 1 trial of its candidate HIV vaccine in Africa, where the burden of the virus is still being keenly felt.

IAVI (the International AIDS Vaccine Initiative) has started screening subjects to be included in the study, called IAVI G003, at centres in Rwanda and South Africa, said the biotech.

Moderna’s vaccines deliver HIV-specific antigens discovered by researchers at IAVI and Scripps Research that have already been tested in a proof-of-concept study carried out last year using an adjuvant protein vaccine approach.

There are hopes that its mRNA approach, which proved so effective against COVID-19, could succeed where traditional vaccine technologies have failed in HIV.

One candidate – mRNA-1644 – has already shown its potential in an earlier phase 1 trial (IAVI G001) run in the US. It codes for an antigen called eOD-GT8 60mer and, in the study, stimulated a targeted B-cell immune response in 97% of vaccine recipients.

Moderna says that B-cell activation should lead to the induction of broadly neutralising antibodies (bnAbs), widely considered to be a goal of an efficacious HIV vaccine, but that immunising with eOD-GT8 60mer alone will almost certainly not be sufficient.

The biotech is looking at a combination regimen of vaccines targeting different HIV immunogens such as Core-g28v2 60mer to try to boost the immune response further against HIV and improve the protective efficacy.

Earlier this year, the first healthy volunteers were dosed with mRNA-1644 in a second phase 1 trial (IAVI G002), which is being funded in part by the Bill & Melinda Gates Foundation and is being carried out in US populations.

IAVI G003 will enrol 18 healthy HIV-negative adult volunteers who will receive two doses of the eOD-GT8 60mer mRNA shot. They will be followed for six months to gauge the safety and immunogenicity of the vaccine.

Moderna said the trial is a “first-in-Africa” study, evaluating an mRNA-delivered HIV immunogen in Africa with African researchers leading the project.

Despite more than 30 years of research, the tendency of the virus to mutate means that classical approaches to vaccine design have been ineffective, and at least four prior vaccine candidates have failed in clinical trials.

In February, one of the front-runner candidates in the decades-long quest to find an HIV vaccine – Johnson & Johnson – reported that its candidate failed a phase 2b trial.

The Ad26.Mos4.HIV vaccine – which uses the same adenoviral technology as J&J’s COVID-19 vaccine and targets four HIV antigens – showed that the shot was safe but unable to meet its target of reducing transmission of HIV by 50%.

And last year, the HVTN 702 study of two co-administered HIV candidate vaccines from Sanofi Pasteur and GlaxoSmithKline, combined with GSK’s adjuvant MF59, was also discontinued due to a lack of efficacy.

The post Moderna’s HIV vaccine prepped for trials in Africa appeared first on .

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Government

Report: Pfizer, NIH Discussing Study of Longer Paxlovid Dosing Regimen

With increasing concerns about COVID-19 reinfection, Pfizer and the National Institutes of Health are discussing potential studies regarding a longer treatment…

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Report: Pfizer, NIH Discussing Study of Longer Paxlovid Dosing Regimen

With increasing concerns about COVID-19 reinfection, Pfizer and the National Institutes of Health are discussing potential studies regarding a longer treatment period with the antiviral medication, Paxlovid.

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases and scientific adviser to the White House, said the plan for the new studies could come over the next few days, Reuters reported this afternoon. During a White House briefing on COVID-19, Fauci pointed out that the rising cases of COVID-19 driven by an Omicron sub-variant are increasing the use of Pfizer’s Paxlovid. So far, more than 660,000 courses of Paxlovid have been administered across the U.S., Reuters said.

However, there is a growing concern that some patients are not shaking the virus as quickly as expected following a treatment regimen of the antiviral. Some continue to experience symptoms, or see a recurrence of their COVID-19 symptoms, following treatment with Paxlovid, Reuters said. Currently, there is no clear indication on the number of patients who are experiencing such a recurrence, or whether or not it is due to the variant type of COVID-19. But, the numbers appear to be enough to warrant such a conversation between America’s top infectious disease expert and Pfizer.

Paxlovid was granted Emergency Use Authorization from the U.S. Food and Drug Administration in December. It was granted EUA for the treatment of high-risk adults and pediatric patients 12 years and older who have been diagnosed with COVID-19 and are at serious risk of hospitalization. A combination of nirmatrelvir and ritonavir tablets, during clinical trials, Paxlovid significantly reduced the risk of hospitalization or death by 89% compared to placebo in non-hospitalized, high-risk adults with COVID-19 within three days of symptom-onset. However, even then, there were cases of a recurrence of symptoms in some clinical trial patients.

Pfizer Chief Executive Officer Albert Bourla has suggested that those patients who experience a recurrence of symptoms should undergo a second round of treatment with Paxlovid. As BioSpace previously reported, Bourla said if symptoms reoccur, “then you give a second course, like you do with antibiotics, and that’s it.”

However, the FDA has balked at that suggestion. Dr. John Farley, director of the FDA’s Office of Infectious Diseases, argued that there is no evidence of benefit for a longer course of treatment, such as 10 days instead of the current five days of administration, or a second five-day round of treatment.

Mark Van Scyoc/Shutterstock

While Pfizer may undertake these additional studies, as BioSpace reported earlier Wednesday, the pharma giant has so far reportedly resisted requests to use Paxlovid in combination studies. The nonprofit Drugs for Neglected Diseases Initiative said that Pfizer rejected a January request to offer doses of Paxlovid to be used in a study alongside an inhaled steroid in Africa.

Also Wednesday, Indianapolis-based Eli Lilly said studies have confirmed that bebtelovimab, the company’s monoclonal antibody against COVID-19, is effective against all variants of the SARS-CoV-2 virus, including BA.2, which is currently the dominant strain in the U.S., Seeking Alpha reported.

 

BioSpace source:

https://www.biospace.com/article/pfizer-nih-in-talks-to-begin-study-of-longer-paxlovid-dosing-regimen

 

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Government

Missouri Bill Prevents Doctors Being Disciplined If They Prescribe Ivermectin Or Hydroxychloroquine

Missouri Bill Prevents Doctors Being Disciplined If They Prescribe Ivermectin Or Hydroxychloroquine

Authored by Naveen Athrappully via The…

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Missouri Bill Prevents Doctors Being Disciplined If They Prescribe Ivermectin Or Hydroxychloroquine

Authored by Naveen Athrappully via The Epoch Times (emphasis ours),

Missouri lawmakers passed legislation that prevents state licensing boards from disciplining doctors who prescribe ivermectin and hydroxychloroquine.

Missouri Gov. Mike Parson signs a bill in Jefferson City, Mo., on May 24, 2019. (Summer Balentine/AP Photo)

Sponsored by Rep. Brenda Kay Shields (R-Mo.), HB 2149 also bars pharmacists from questioning doctors or disputing patients regarding the usage of such drugs and their efficacy.

With a convincing 130–4 vote in the House, HB 2149 passed both chambers on May 12 and currently heads to the office of Gov. Mike Parson to be potentially signed into law.

The board shall not deny, revoke, or suspend, or otherwise take any disciplinary action against, a certificate of registration or authority, permit, or license required by this chapter for any person due to the lawful dispensing, distributing, or selling of ivermectin tablets or hydroxychloroquine sulfate tablets for human use in accordance with prescriber directions,” reads the draft of the bill (pdf).

It adds, “A pharmacist shall not contact the prescribing physician or the patient to dispute the efficacy of ivermectin tablets or hydroxychloroquine sulfate tablets for human use unless the physician or patient inquires of the pharmacist about the efficacy of ivermectin tablets or hydroxychloroquine sulfate tablets.”

Critics of the bill have noted that the Food and Drug Administration (FDA) has not given approval for usage of the drugs. Ivermectin and hydroxychloroquine have been divisive drugs and politically polarized throughout the pandemic.

“But, nevertheless, the Missouri legislature has chosen to ‘own the libs’ by issuing a gag order against every pharmacist in this state from offering their medical opinion on taking either one of those medications—even if it could kill their patient,” wrote former Democratic nominee Lindsey Simmons in a May 12 Twitter post.

Although 22 countries across the world have approved the use of ivermectin in treating COVID-19, the FDA maintains that the current data show the drug to be ineffective. Large doses can be dangerous, it says.

A recent study published in the International Journal of Infectious Diseases analyzed a national federated database of adults that compared ivermectin with the FDA-approved COVID-19 medication, remdesivir.

After using propensity score matching and adjusting for potential confounders, ivermectin was associated with reduced mortality vs remdesivir,” researchers wrote. “To our knowledge, this is the largest association study of patients with COVID-19, mortality, and ivermectin.”

According to The Associated Press, Missouri state Rep. Patty Lewis, a Democrat, agreed to the bill to satisfy a group of conservatives in the Senate. She added that the bill will not change anything significantly as medical boards do not engage in punishing doctors who prescribe drugs legally.

Tyler Durden Wed, 05/18/2022 - 23:25

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