Moderna R&D Day: Expands the Field of mRNA Medicine

 

• Company's flu vaccine, mRNA-1010, met its primary endpoint in Phase 3 trial; separate Phase 1/2 data demonstrated higher HAI titers than Fluzone HD
• Vaccine pipeline advancing rapidly with Company announcing the completion of RSV BLA filing (mRNA-1345), completion of adult enrollment in the Phase 3 trial of mRNA-1647, a first-in-class vaccine against CMV, and the Phase 3 trial of mRNA-1283, a next-generation COVID-19 vaccine
• With its partner Merck, the Company plans to begin a second Phase 3 trial of mRNA-4157, its individualized neoantigen therapy (INT), in combination with Keytruda®, for non-small cell lung cancer later this year; updated efficacy follow-up from the ongoing Phase 2 study in adjuvant melanoma expected in Q4
• With positive clinical data announced in mRNA-3705, a treatment for methylmalonic acidemia, the Company has three chronic rare disease medicines that have demonstrated potential for clinical benefit in patients
• Over the next five years, the Company expects to launch up to 15 new products addressing high unmet needs, to bring up to 50 new candidates into clinical trials and to continue expanding the field of mRNA into new applications

https://www.biospace.com/article/releases/moderna-expands-the-field-of-mrna-medicine-with-positive-clinical-results-across-cancer-rare-disease-and-infectious-disease/

Q32, Horizon Start Phase 2 Trial of Bempikibart (formerly ADX-914) for Severe Alopecia Areata

Q32 Bio, a clinical stage biotechnology company developing biologic therapeutics to restore immune homeostasis, and Horizon Therapeutics plc (Nasdaq: HZNP), today announced that the first patient has been dosed in a randomized, double-blind, placebo-controlled, Phase 2 multicenter, proof-of-concept study to evaluate bempikibart in adult patients with severe alopecia areata. Q32 Bio and Horizon are collaborating to develop bempikibart, a fully human anti-IL-7Rα antibody that re-regulates adaptive immune function by blocking signaling mediated by both IL-7 and TSLP, two key immune pathways.

https://www.biospace.com/article/releases/q32-bio-and-horizon-therapeutics-plc-announce-dosing-of-first-patient-in-phase-2-trial-of-bempikibart-formerly-adx-914-for-severe-alopecia-areata/

Forensic Analysis Of Deaths In Pfizer's Early mRNA Vaccine Trial Found Significant Inconsistencies

 by Megan Redshaw, JD via The Epoch Times (emphasis ours),

A group of researchers are calling into question Pfizer’s and BioNTech’s early trial data on its original COVID-19 vaccine after a forensic analysis revealed significant inconsistencies between data in the companies’ six-month interim report and publications authored by Pfizer/BioNTech trial site administrators.

The preprint, published on Sept. 4, showed trial subjects vaccinated with Pfizer’s COVID-19 vaccine experienced a 3.7 times increase in cardiovascular deaths compared to placebo controls—a “significant adverse event signal” not disclosed by Pfizer when the vaccine was authorized for emergency use. In addition, the analysis found numerous instances where Pfizer/BioNTech attributed potential vaccine-associated deaths to other causes and undermined vaccine safety data.

Clinical Trial ‘Cause of Death’ Unsupported by Documentation

Researchers assessed data from Pfizer’s original phase two/three clinical trial involving 44,060 subjects equally divided into two groups. One group received a dose of Pfizer’s COVID-19 vaccine, and the other received a placebo. As part of their analysis, researchers reviewed the cause of death forms (CRFs) of 38 trial subjects who died during the study period from July 27, 2020, to March 13, 2021, the end date of the clinical trial.

They found that 14 of the 38 deaths—more than one-third of deaths—resulted from cardiovascular events, accounting for the difference between the 21 deaths in the vaccination arm compared to the 17 deaths in the placebo arm. In numerous cases, researchers found that documentation did not support the cause of death diagnosis or allow one to rule out the possibility of a cardiovascular event with an autopsy.

“In general, our review of the CRFs found them to be lacking in detail and extremely difficult to interpret and develop a good timeline of events,” researchers wrote. “Often, a subject’s pre-trial clinical history was absent. Absent also were results of the extensive array of medical testing carried out at the pre-trial screening and at other regularly scheduled visits.”

Absent test results included complete blood counts, metabolic tests, pregnancy tests, COVID-19 tests, a comprehensive list of active medications, and other tests that would have provided clarity on a subject’s overall health. Although more detailed clinical data on the trial subjects exists, the researchers said it is being withheld. Given the limitations of what Pfizer provided, the researchers said the information in the CRFs was often insufficient to support the investigator’s conclusions regarding the cause of death.

The researchers also noted frequent communications between Pfizer/BioNTech physicians and trial site medical staff about the CRFs, some of which were over 400 to 900 pages.

Pfizer Used Earlier Data Cutoff and Unblinded Control Group

According to the analysis, Pfizer excluded the 38 deaths from information provided to the U.S. Food and Drug Administration (FDA) during its December 2020 meeting where its vaccine advisory panel was considering whether to authorize the Pfizer/BioNTech vaccine for emergency use.

When Pfizer/BioNTech submitted its application for Emergency Use Authorization (EUA) on Nov. 20, 2020, to the FDA, the application described clinical trial results using a cutoff date of November 14, 2020, even though the end date of the trial was March 13, 2021. Researchers said the earlier cutoff date concealed mortality data from the clinical trial.

“Both Pfizer presenters and the FDA committee failed to ask for and review deaths that occurred in the clinical trial participants after the data cutoff. As a result, they missed a more than three-fold increased risk of cardiovascular death with the Pfizer-BioNTech COVID-19 vaccine,” cardiologist Dr. Peter McCullough told The Epoch Times in an email.

“If the FDA presentation with core slides had been presented with accurate, updated data, the Pfizer COVID-19 vaccine should not have been approved because of safety concerns,” he added.

Twenty weeks into the clinical trial on Dec. 11, 2020, Pfizer’s COVID-19 vaccine received EUA from the FDA, and the agency allowed Pfizer to unblind its control group. Unblinding occurs when study participants are told whether they received a vaccine or a placebo, and placebo subjects are permitted to get vaccinated. All but a few chose to receive the vaccine.

https://www.zerohedge.com/covid-19/forensic-analysis-deaths-pfizers-early-mrna-vaccine-trial-found-significant

COVID Cancellations Are Back: California High Schools Cancel Football Games

 by Jack Phillips via The Epoch Times (emphasis ours),

Two California high schools have confirmed that they canceled football games because of COVID-19 cases among students.

Esparto High School near Sacramento confirmed that it canceled a game after it stated that six players tested positive for COVID-19. It also stated that multiple players were also injured and that it didn't have enough players for a game.

This comes as there have been concerns that virus-related rules might be reimplemented in the coming months.

“Ensuring the well-being of students is not only a moral obligation but also a legal and ethical responsibility,” district Superintendent Christina Goennier told affiliate station FOX40.

Dr. Aimee Sisson, the Yolo County health officer, told the outlet that she supports the move.

“Our role in the health department is to support our schools in being able to stay open for that in-person instruction,” she said. “We provide support certain tips on what to do when there are cases provide testing resources. But really our goal for this school year is to keep kids in school in person, but also to do so safely.”

Hundreds of miles away, a high school north of Los Angeles also confirmed to local media outlets that it canceled a football game against a rival school after multiple COVID-19 cases were confirmed among its players.

“We have an outbreak,” Santa Paula Assistant Principal Daniel Guzman told the Ventura County Star. “The number is rising.”

Mr. Guzman was referring to multiple cases among its football and cheerleading squads.

“Football is part of our little town’s DNA,” he said. “[But] student safety is a priority above all.”

The cancelations come as a public elementary school in Montgomery County, Maryland, stated that it reinstated mask requirements for "students and staff in identified classes or activities" after several students tested positive. Officials said it would involve a kindergarten class.

"Since last Friday, more students and staff members have reported new cases of COVID-19, with classroom outbreaks occurring in a few schools across the county. This rise in COVID-19 cases is not unexpected, as our community gathers together, following a modest summer surge," a school health official, Patricia Kapunan, wrote in a letter.

As reported by WUSA9, according to the letter, "measures may be temporarily introduced during outbreaks, including screening testing, distancing, and masking to control spread in a specific space where transmission is high," and "students who cannot safely and consistently mask due to young age, a medical condition, or developmental disability are not required to do so."

In a later report, Montgomery County Executive Marc Elrich said no mask mandate is in effect for schools or any government officials in the county, which is located adjacent to Washington.

"Our concern would be if we start seeing a lot of people in the hospital, a lot of people go into ICU, not just in the hospital, but intensive care, and if our deaths click up. Then, we'll be looking at mandates," he said. "But what we're going to be asking people to do is if you know you're at risk and you're in a crowded place, you should start wearing a mask again."

Several schools in Alabama have also reintroduced mask-wearing amid reports of an increase in COVID-19 cases. In Dallas County, Alabama, a probate judge told local media outlets that masks will be mandated in offices that have interaction with the public.

In August, multiple hospitals also reimplemented mandates or mask recommendations in several states, including in Upstate New York, California, and Massachusetts.

The mandates drew condemnation and concerns from several prominent Republicans, including former President Donald Trump and Florida Gov. Ron DeSantis. In a press conference several days ago, Mr. DeSantis said his state won't reimplement mandates, and the former president released a video calling on Americans to resist COVID-19 lockdowns, mandates, and other requirements that he likened to tyranny.

"They want to restart the COVID hysteria so they can justify more lockdowns, more censorship, more illegal drop boxes, more mail-in ballots, and trillions of dollars in payoffs to their political allies heading into the 2024 election—does that sound familiar?" the former commander-in-chief said in a video in late August.

"To every COVID tyrant who wants to take away our freedom, hear these words: We will not comply, so don't even think about it. We will not shut down our schools; we will not accept your lockdowns; we will not abide by your mask mandates; and we will not tolerate your vaccine mandates."

Over the weekend, former White House official Dr. Anthony Fauci, while defending masks in the face of studies that say they're ineffective, said it's possible that mask recommendations may be given again but that a mandate is unlikely.

"I don't see there being, certainly not federal mandates—I would be extremely surprised if we would see that," he told ABC News.

https://www.zerohedge.com/political/covid-cancellations-are-back-california-high-schools-cancel-football-games

Alnylam to be halted as FDA panel reviews treatment for Cardiomyopathy of ATTR Amyloidosis

 Alnylam Pharmaceuticals Inc. (ALNY) said Wednesday its stock will be halted on Nasdaq through the day as a regulatory advisory committee will meet to review its new drug application for a treatment for the Cardiomyopathy of ATTR Amyloidosis. The treatment called onpattro, or patisiran, is approved in the U.S. and Canada for the treatment of the polyneuropathy of hereditary ATTR (hATTR) amyloidosis in adults. ATTR is a progressive, debilitating and fatal disease caused by misfolded transthyretin (TTR) proteins, which accumulate as amyloid deposits in various parts of the body, including the nerves, heart and gastrointestinal tract. Patients can have polyneuropathy, cardiomyopathy, or both manifestations of the disease. There are two different forms of ATTR amyloidosis -- hereditary ATTR (hATTR) amyloidosis, which is caused by a TTR gene variant and affects approximately 50,000 people worldwide, and wild-type ATTR (wtATTR) amyloidosis, which occurs without a TTR gene variant and impacts an estimated 200,000 -- 300,000 people worldwide, according to Alnylam. The FDA advisory panel will meet at 9:00 a.m. ET. The FDA has set an Oct. 8 action date for the application. Alnylam's stock is down 11% in the year to date, while the S&P 500 has gained 16.2%.

https://www.morningstar.com/news/marketwatch/20230913256/alnylam-pharmaceuticals-stock-to-be-halted-wednesday-as-fda-advisory-panel-reviews-treatment-for-the-cardiomyopathy-of-attr-amyloidosis

Pullback Buying Opportunity For Blood Cancer Firm Geron: Goldman

 Goldman Sachs has upgraded Geron Corporation GERN to Buy from Neutral, with a price target of $4.

Recently, the FDA assigned a standard review and a Prescription Drug User Fee Act (PDUFA) action date of June 16, 2024, for Geron's New Drug Application (NDA) for imetelstat for transfusion-dependent anemia in patients with lower-risk myelodysplastic syndromes. 

In addition, the FDA informed that it plans to hold an advisory committee meeting.

The analyst says that imetelstat will likely be approved in this setting, with unadjusted peak sales of $1.5 billion (probability of success of 90%).

Further, the recent approval of Bristol-Myers Squibb & Co BMY Reblozyl (luspatercept) in frontline LR-MDS across a broad population (RS+/-) does not negate the blockbuster opportunity for imetelstat in the second-line setting.

Thus, the recent pullback in shares (-22.5% m/m) has presented a buying opportunity for the stock. 

Goldman analysts note that imetelstat has followed an extensive development journey marked by numerous clinical setbacks across various cancer types. 

Particularly noteworthy was a pilot study in myelofibrosis, which revealed both clinical effectiveness and significant adverse events, including hematological complications and liver-function irregularities. 

In anticipation of the upcoming AdCom meeting, these safety findings from the previous study are expected to be a key topic of discussion. 

However, it's worth noting that more recent data from GERN regarding imetelstat's use in LR-MDS presents a different safety profile compared to the earlier challenges. 

This divergence may be attributed to several factors, including GERN's adjustment of the dosing regimen for LR-MDS and extended dosing intervals. Additionally, differences in the patient population and the nature of the underlying disease could contribute to the distinct safety profile observed in LR-MDS.

https://www.benzinga.com/analyst-ratings/analyst-color/23/09/34495981/recent-pullback-buying-opportunity-for-blood-cancer-firm-geron-goldman-sachs

First Case Of White Dot Syndrome Emerged After COVID Vaccine And Subsequent Infection, Study Shows

 by Mary Gillis via The Epoch Times (emphasis ours),

Scientists from New Zealand have uncovered the first case of a rare eye disease linked to both the COVID-19 vaccine and the virus itself, a new study published in the Journal of Ophthalmic Inflammation and Infection reveals.

A 28-year-old otherwise healthy patient was diagnosed with multiple evanescent white dot syndrome (MEWDS) after complaining of vision problems just two days after receiving her second dose of the Pfizer-BioNTech vaccine.

The woman’s symptoms included dark blind spots, phantom light flashes, and overall decreased vision—all specific to her right eye.

According to the study, doctors discovered that the vision in her right eye went from 20/20 to 20/50. In addition, her eye tissue was torn, optic nerves were swollen, and multiple pale-colored lesions were scattered throughout the back of her eye.

A) Wide-field color fundus photo; B) Fundus infrared image of the right eye; C) OCT macula in a patient with multiple evanescent white dot syndrome associated with COVID-19 vaccination. (Courtesy of Hannah W. Ng and Rachael L. Niederer; Journal of Ophthalmic Inflammation and Infection)

After three months and without treatment, vision in her right eye returned to normal, and all other symptoms subsided.

One year later, the woman showed similar symptoms and was once again diagnosed with MEWDS, only this time in the left eye. Symptoms emerged seven days after she tested positive for COVID-19, leading researchers to suspect a link between the two events.

Similar to the first instance, no treatment was required, and symptoms resolved after nine months.

What Is MEWDS?

According to the study, MEWDS dates back to 1984 and is considered an idiopathic inflammatory disease of the outer retina that occurs spontaneously and without concrete explanation. It is thought to be an autoimmune response.

It often occurs in young, myopic women, with a mean age of 28. However, it is also seen among people over 65.

MEWDS patients may have flu-like early symptoms that include:

• Visual disturbances such as flashes of light.
• Sudden, painless decline in central acuity in one eye.
• Partial color blindness.

It can be bilateral in some cases.

https://www.zerohedge.com/medical/first-case-white-dot-syndrome-emerged-after-covid-19-vaccine-and-subsequent-infection-study