One COVID Vaccine Held Up Best Over Time: CDC Study

 In terms of preventing COVID-related hospitalizations, the two-dose mRNA vaccines from Pfizer (Comirnaty) and Moderna offered the best protection upfront and over time, a case-control analysis involving data from 21 U.S. hospitals showed.

From March to August 2021, the vaccine effectiveness (VE) against COVID-19 hospitalizations landed at 93% for the Moderna vaccine, 88% for Pfizer's, and 71% for Johnson & Johnson's (J&J), reported Wesley Self, MD, of Vanderbilt University Medical Center in Nashville, Tennessee, and colleagues, writing in the Morbidity and Mortality Weekly Report.

After 120 days from the time of vaccination, however, Moderna's VE against hospitalization only dipped to 92%, a non-significant decline, while Pfizer's dropped to 77% (P<0.001).

"Differences in VE between the Moderna and Pfizer-BioNTech vaccine might be due to higher mRNA content in the Moderna vaccine, differences in timing between doses (3 weeks for Pfizer-BioNTech versus 4 weeks for Moderna), or possible differences between groups that received each vaccine that were not accounted for in the analysis," Self and co-authors suggested.

No data were shown for the J&J shot after 120 days due to the limited number of patients who received the vaccine, but the VE rate dipped to 68% for the single-dose vaccine after 28 days.

A second analysis in the study, involving 100 patients, showed that individuals vaccinated with the one-dose J&J viral vector vaccine had lower anti-SARS-CoV-2 antibody levels at 2 to 6 weeks after being fully vaccinated compared with the mRNA vaccine recipients. Antibody levels were slightly higher with Moderna's versus Pfizer's.

"Although an immunologic correlate of protection has not been established for COVID-19 vaccines, antibody titers after infection and vaccination have been associated with protection," the group wrote.

The findings came from a sample of 3,689 adults without immunocompromising conditions (1,682 case patients and 2,007 controls) admitted with COVID-19 to one of 21 U.S. hospitals across 18 states from March 11 to August 15. Median patient age was 58 years and a little less than half were women, while 53% were white, 23% were Black, and 18% were Hispanic.

Overall, 20% were fully vaccinated with Pfizer's vaccine, 12.7% with Moderna's, and 3.1% with the J&J vaccine; 64.0% were unvaccinated.

Limitations of the study included that it was limited to non-immunocompromised adults, the limited number of J&J recipients, and that follow-up time after being fully vaccinated was only about 29 weeks. Notably, data on VE were not evaluated by SARS-CoV-2 variant, including the Delta variant.

Disclosures

Self disclosed relationships with Merck and Aerpio Pharmaceuticals. Co-authors reported various grant support and relationships with industry.

Primary Source

Morbidity and Mortality Weekly Report

Source Reference: Self WH, et al "Comparative effectiveness of Moderna, Pfizer-BioNTech, and Janssen (Johnson & Johnson) vaccines in preventing COVID-19 hospitalizations among adults without immunocompromising conditions -- United States, March–August 2021" MMWR 2021; DOI: 10.15585/mmwr.mm7038e1.

https://www.medpagetoday.com/infectiousdisease/covid19vaccine/94577

Incyte Jakafi sister med clears FDA for atopic dermatitis, with safety warning

 Months into extended FDA reviews that clouded an entire drug class, Incyte has finally snagged a go-ahead for ruxolitinib cream, key for the company’s diversification plan beyond Jakafi. But a less-than-ideal label that tags several serious safety warnings spells trouble for its commercial rollout.

To be sold under the brand name Opzelura, ruxolitinib cream is now cleared to treat mild to moderate atopic dermatitis in patients 12 years or older who aren’t suitable for or have failed other topical prescription drugs, Incyte said Tuesday.

While Opzelura is celebrated as the first topical formulation of a JAK inhibitor to enter the market, its approval comes with a classwide black box warning that has been added to oral JAKs about serious infections, death, cancer, heart-related events and blood clots. Some of the items are theoretical problems for the cream, as they have so far turned up in oral JAK inhibitors, while other issues reflect observations from JAKs for inflammatory conditions.

Incyte had previously expected a relatively clean label for Opzelura despite increased FDA scrutiny on the entire JAK inhibitor class. Jakafi, the oral formulation of ruxolitinib, treats blood cancer and transplant rejection and was spared from the label restrictions the FDA recently added to oral JAKs treating inflammatory diseases.

Despite the boxed warnings, Incyte expects Opzelura could reach at least $1.5 billion in peak sales, Todd Edwards, the company’s head of inflammation and autoimmunity business unit, told investors during a call Wednesday. The calculation comes from an estimate that patients will use about three to four tubes of 60-mg Opzelura a year at a per-unit wholesale acquisition cost of $1,950.

Wall Street pegged Opzelura to reach $1.5 billion in sales by 2030, but SVB Leerink analyst Andrew Berens figured the number is too high, putting his estimates at $600 million by 2030.  

For his part, RBC Capital Markets analyst Brian Abrahams marked $550 million for the drug’s peak U.S. sales for atopic dermatitis. In a Tuesday note to clients, he stressed that payer formulary position “will be critical for gauging ultimate revenue potential.” In a survey Abrahams’ team did in February, 36% of 40 dermatologists said they view reimbursement as the biggest hurdle to the use of atopic dermatitis therapies.

Analysts in general are having a hard time pinning a definite answer to how Opzelura might perform. On the one hand, the black box could be a serious blow; RBC’s physician survey showed that a similar warning for Opzelura as the oral JAKs could cut the cream’s adoption by 33%. The RBC team argued the reduction would mostly affect the mild patient population. Before the FDA’s safety review of oral JAKs, Incyte’s own physician survey found 85% of dermatologists indicated they would likely give Opzelura to their patients. A more recent survey by the company suggested dermatologists would reduce use by 15% in the case of a boxed warning.

What’s more, poor commercial performance of other branded topical eczema drugs such as Pfizer’s once blockbuster hopeful Eucrisa doesn’t really offer pharma watchers confidence in Opzelura. Cheap, generic topical corticosteroids are widely used for eczema.

But on the other hand, physicians expressed enthusiasm for Opzelura given its strong efficacy and lack of topical options. In its two phase 3 TRuE-AD trials, twice-daily Opzelura helped significantly more patients achieve clearer skin and reduce itch compared to nonmedicated cream. After eight weeks of treatment, 53.8% of Opzelura takers in TRuE-AD1 and 51.3% in TRuE-AD2 enjoyed clear or almost clear skins, versus 15.1% and 7.6% for the control patients in the two trials, respectively.

The recent boxed warnings the FDA slapped on the labels of Pfizer’s Xeljanz, AbbVie’s Rinvoq and Eli Lilly’s Olumiant indicate the agency’s cautionary stance on the three oral JAK inhibitors, which came after a large postmarketing study for Xeljanz in rheumatoid arthritis noted safety signals. While the FDA dug into findings from the Xeljanz study, the agency had delayed its decisions on Opzelura as well as atopic dermatitis rulings for Rinvoq, Olumiant and Pfizer’s investigational abrocitinib.

Abrahams, in his February note, suggested the oral JAKs “appeared to have more of a potential role in severe patients who would otherwise receive biologics,” while Opzelura could become “the preferred agent” in moderate disease.

Opzelura is broadly viewed as Incyte’s key program to diversify away from Jakafi before the oral med falls off the patent cliff in 2027, Evercore ISI analysts noted in their analysis Tuesday. Jakafi’s revenues of $529 million made up 76% of Incyte’s total haul in the second quarter. Now, with Opzelura’s boxed warnings, Incyte will likely turn to striking deals, the analysts said.

In addition to atopic dermatitis, Opzelura recently hit its goal in two phase 3 trials in vitiligo. For eczema, Opzelura is currently indicated for “short-term and noncontinuous chronic treatment,” but the Evercore ISI team pointed out that vitiligo requires more chronic treatment. During Wednesday’s call, Incyte said the intermittent dosing description is only reflecting the eczema clinical trial design and that it expects a potential vitiligo indication to have its own dosing.

https://www.fiercepharma.com/pharma/incyte-s-jakafi-sister-med-clears-fda-for-atopic-dermatitis-but-safety-warning-a-heavy-cross

Hospital ordered to treat COVID patient with ivermectin says drug could damage her health

 A Chicago-area hospital is pushing back on the use of the drug ivermectin as a treatment for COVID-19 after it said its administration caused a female patient’s heart rate to drop dramatically following a “mega dose” of the drug, the Chicago Tribune reports. 

The hospital, the Advocate Condell Medical Center in Libertyville, Ill.,, will head to court on Wednesday afternoon to argue that using the controversial drug as a treatment for the coronavirus could cause further health problems for the patient.

Attorneys for the patient, Leslie Pai, say that the hospital staff misinterpreted the prescription dosage and that her medical records don’t indicate a significant drop in her heart rate. They argue that Pai is responding well to the treatment with ivermectin.

Ivermectin made headlines when it began being authorized for use as a COVID-19 treatment. Health regulatory agencies say that it is usually used as a medicine for treating various infections caused by internal and external parasites, and that it has been used on both animals and humans.

The Centers for Disease Control and Prevention (CDC) issued a statement on its use as a COVID-19 medication in August, warning the U.S. Food and Drug Association (FDA) has not approved its use for treating COVID-19 infections and that reports of adverse effects and overdoses have increased.

The Tribune reported that the family of Pai, a 68-year-old photographer, has been pushing in court to have her receive ivermectin.

Pai’s daughter, Tiffany Wilson, had her transferred to Advocate Condell from another hospital after it opposed the use of ivermectin. After Advocate Condell initially refused the use of ivermectin, Wilson sued in DuPage County. While Advocate Condell Medical Center is in Lake County, its parent company is in DuPage County, where judges in at least two decisions have issued rulings siding with patients who have requested that they be treated with ivermectin.

On Friday, the Tribune reported, DuPage County Judge Ann Hayes granted a temporary injunction that allowed an outside physician to give Pai ivermectin.

Affidavits filed by the hospital’s lawyers stated that Pai’s condition did not improve from the treatment, and that after one dose her pulse fell to 28 beats per minute, requiring ICU staff to administer norepinephrine, the Tribune reported.

“In my expert medical opinion … without the intervention of Advocate Condell Medical Center ICU staff, Ms. Pai was at risk of heart failure, stroke, death and other significant harm,” attending physician Harvey Friedman wrote.

The hospital sent a statement to The Tribune, saying that while the staff has sympathy for Pai and her family, the staff “do not support or recommend the administration of ivermectin for treatment of COVID-19. We stand with our care team in recommending other proven courses of treatment which have worked safely and effectively for thousands of patients.”

The Tribune reported that it could not reach Wilson for comment, but that in an affidavit she said her own research had indicated the risks of ivermectin were “infinitesimally small.”

https://thehill.com/homenews/state-watch/573394-hospital-ordered-to-treat-covid-19-patient-with-ivermectin-says-drug

OraSure cut to Market Perform from Outperform by Raymond James

 Target $22

https://finviz.com/quote.ashx?t=OSUR

Device maker Cardiovascular Systems warns of hit to sales from Delta variant

 Medical device maker Cardiovascular Systems Inc on Wednesday warned of lower-than-expected sales in the first quarter, as the Delta variant of the coronavirus threatens to dent the recovery in demand for non-urgent surgeries.

The U.S.-based company, which makes products used in heart procedures, said increased hospitalizations in Florida, Texas and other heavily impacted areas has constrained the capacity of hospitals to conduct procedures that use its products.

The company did not withdraw or update its fiscal-year forecast, but said https://bit.ly/3CzwGa9 in a regulatory filing that it expected the impact to be greater than 10% from its prior expectations.

The company in August had forecast fiscal-year 2022 sales of between $295 million and $305 million.

Larger rival Medtronic Plc had also said last month that it expected infections from the Delta variant to peak in the next few weeks, while noting that demand for devices used in heart procedures have been hit recently. 

https://finance.yahoo.com/news/device-maker-cardiovascular-systems-warns-131058920.html

COVID Vaccine Using Dynavax Adjuvant Meets Efficacy Endpoints in Global Phase 2/3 Trial

 - Global Phase 2/3 SPECTRA Trial enrolled over 30,000 adult and elderly participants across 4 continents; 100% of SARS-CoV-2 strains observed in efficacy analysis were variants

- 100% efficacy against severe COVID-19 and hospitalizations, and 84% efficacy against moderate-to-severe COVID-19 caused by any strain of SARS-CoV-2

- Favorable safety profile; no significant differences in systemic adverse events or severe/serious adverse events compared to placebo

- The impressive results in efficacy and tolerability reflect the beneficial profile of CpG 1018 as a valuable vaccine adjuvant

https://finance.yahoo.com/news/covid-19-vaccine-developed-clover-110500740.html

CMS Approves Clover Health's Expansion Plans for 2022

 Expansion marks Clover’s entry into Alabama and nearly doubles company’s geographic footprint based on number of counties

Clover Health (Nasdaq: CLOV) (“Clover”), a technology company committed to improving health equity for America’s underserved seniors, announces that the Centers for Medicare and Medicaid Services (CMS) has approved the company’s service area expansion to operate in 101 new counties.

With this approved service area expansion beginning January 1, 2022, Clover’s Medicare Advantage (MA) plans will be available to eligible individuals in 101 new counties across Georgia, New Jersey, South Carolina, Texas, and Alabama – a new state for the company. This will bring Clover’s total coverage area for its Medicare Advantage plans to 209 counties across nine states. Individuals eligible for Medicare in any of the 209 counties can sign up for Clover’s plans during the Annual Election Period, which runs from October 15 to December 7.

“With CMS’ approval of our significant expansion efforts, we will be bringing affordable, wide network plans to additional previously underserved communities, which we believe is the key to achieving health equity for America’s aging population. Nearly doubling our service counties in one year demonstrates the differentiated scalability of our approach as compared to certain other plans which are constrained to narrow service areas orbiting specific providers,” said Andrew Toy, President of Clover.

The list of new 2022 counties includes:

Alabama	Chambers, Cherokee, Clay, Cleburne, Macon, Randolph, Russell
Georgia	Baker, Banks, Barrow, Berrien, Brantley, Brooks, Burke, Calhoun, Camden, Carroll, Catoosa, Chattahoochee, Chattooga, Clarke, Clay, Colquitt, Columbia, Cook, Coweta, Crisp, Dade, Decatur, Dougherty, Echols, Elbert, Fannin, Fayette, Franklin, Gilmer, Glascock, Grady, Greene, Habersham, Hall, Hancock, Haralson, Harris, Hart, Jackson, Jefferson, Laurens, Lee, Lincoln, Lumpkin, Madison, Marion, McDuffie, Miller, Mitchell, Morgan, Murray, Muscogee, Newton, Oconee, Oglethorpe, Pierce, Putnam, Quitman, Rabun, Randolph, Richmond, Schley, Spalding, Stephens, Stewart, Sumter, Talbot, Taliaferro, Terrell, Thomas, Tift, Troup, Walton, Warren, Webster, White, Wilkes, Worth
New Jersey	Cape May, Sussex
South Carolina	Aiken, Bamberg, Barnwell, Edgefield, McCormick, Calhoun, Orangeburg, Saluda
Texas	Comal, Guadalupe, Wilson, Atascosa, Medina, Bandera https://finance.yahoo.com/news/cms-approves-clover-healths-expansion-130000334.html