Demand for Novo Nordisk's new weight-loss drug Wegovy outstripped early supply

 Novo Nordisk’s GLP-1 empire is on the ascent, courtesy of its diabetes stalwarts Ozempic and Rybelsus, plus its newly-approved obesity drug Wegovy. With momentum building—and facing "substantial" demand for its new weight loss med—the Danish drugmaker is dialing up its performance forecast for the year, CEO Lars Fruergaard Jørgensen said Wednesday. 

During the first six months of 2021, Novo's diabetes and obesity sales grew 13% at constant exchange rates, clocking in at 56.9 billion Danish kroner ($9.05 billion), the company said in an earnings release.

Sales for the company's GLP-1 arsenal, which includes Ozempic and its oral counterpart Rybelsus, leapt 30% at constant currencies.

Meanwhile, sales in obesity care jumped 34% at constant currencies for the six-month period, Novo said. While Novo didn't break out sales for new weight-loss drug Wegovy, Jefferies analysts estimated the med generated between DKK 250 million and DKK 300 million ($40 million to $48 million) after its approval in early June.

Initial demand for the drug in the U.S. has "exceeded supply," Jefferies analysts wrote. That's resulted in temporary delays on the filling of some prescriptions, the Jefferies team said.

But on the flip side, the "initial substantial demand" helped the company raise its expectations for the rest of the year, CEO Jørgensen said in a statement. 

Overall sales for the first half of the year landed at 66.8 billion Danish Kroner ($10.63 billion), signaling a 12% jump over the same period last year. With the performance, Novo expects to chart 10% to 13% sales growth for the full year versus the 6% to 10% it had previously predicted.

While Rybelsus sales grew during the quarter, the med failed to meet consensus analyst expectations. Analysts had estimated the drug would pull in DKK 1.17 billion ($190 million) while it actually generated DKK 950 million ($150 million), the Jefferies team wrote.

https://www.fiercepharma.com/pharma/novo-nordisk-rises-ozempic-sales-as-analysts-say-demand-for-new-obesity-med-wegovy-has

Supply problems solved, Novavax in deal to supply Europe with up to 200M COVID vax doses

 Ironing out production problems has allowed Novavax to finalize a handshake deal with Europe that it made in December to supply its COVID-19 vaccine.

On Wednesday, the European Commission said it approved a deal to purchase 200 million doses of the Maryland-based biotech's protein-based vaccine, which has yet to gain approval in the U.S. or Europe. 

The contract calls for Novavax to provide 100 million vaccine doses, with an option for another 100 million by the end of 2023. The company said it is working to complete the rolling submission to the European Medicines Agency in the third quarter of this year. 

A preliminary agreement on the deal was reached in December, but Novavax delayed its completion because of difficulty securing raw materials to produce the shot. In April, Novavax CEO Stanley Erck told The Observer that a shortage of 2,000-liter bags was a threat to the global supply of vaccines. Around that time, the company altered its projection to be able to supply 150 million vaccine doses per month by the end of June. 

Tiny Novavax has been an unlikely COVID-19 vaccine success story. Despite never bringing a product to the market, the company won a $1.6 billion contract from the U.S. to develop the shot and supply 100 million doses. It also has committed 1.1 billion doses to middle- and low-income countries. 

The move allows Europe to diversify its vaccine stock. After contending with supply problems and safety concerns with the adenovirus vector vaccines produced by AstraZeneca and Johnson & Johnson, the bloc announced that it would not renew contracts with those companies, leaving it heavily dependent on shots from Pfizer-BioNTech and Moderna.

“Our new agreement with Novavax expands our vaccine portfolio to include one more protein-based vaccine, a platform showing promise in clinical trials,” EU Health Commissioner Stella Kyriakides said in a statement.

GlaxoSmithKline and Sanofi, who are partnering on a protein-based vaccine that has yet to be approved, also have signed a supply deal with the EU. The bloc additionally has an agreement in place with CureVac to supply 405 million doses of its mRNA shot, which the company has struggled to develop.

The mRNA shot produced by Pfizer-BioNTech is the overwhelming favorite in Europe. The companies have signed on to supply the bloc with 2.4 billion doses, while Moderna has agreed to provide 460 million shots.  

Earlier this week, the Financial Times reported that Pfizer-BioNTech and Moderna raised the prices of their shots in their most recently signed contracts with Europe.

https://www.fiercepharma.com/pharma/supply-problems-solved-novavax-completes-deal-europe-to-supply-200m-covid-19-vaccine-doses

Fauci Predicts 'Turnaround' in U.S. Pandemic Curve

 Anthony Fauci, MD, chief medical advisor to President Biden, said he anticipates a "turnaround" in the pandemic and a trajectory that mirrors the experience of the U.K., but warned that cases here haven't peaked yet.

During an interview hosted by the Center for Strategic and International Studies (CSIS) on Tuesday, the NIAID director also plugged the launch of the NIH's Antiviral Program for Pandemics, and described his vision of an antiviral that would fight COVID-19.

New Antiviral Program

"I want a pill that blocks a specific viral function," Fauci said. "I want to give it once a day, if possible, I want it to be low in toxicity, and I want it to have very minimal drug-drug interactions."

"Give me that, and I'll be really happy," Fauci told webinar host and interviewer J. Stephen Morrison, senior vice president at CSIS and director of its Global Health Policy Center.

Manufacturing would need to be "scaleable," Fauci stressed, to ensure that low- and middle-income countries would have access to any new therapy, and he underscored the need to factor in variants.

"When you have variants, you've got to be ready," he said, noting that it's unlikely it will be as simple as "one pathogen and one drug that's the knock-out home-run drug. You always have to be ready to continue to develop alternatives that could keep up with the variants."

Asked whether a $3.2 billion program will be enough to incentivize drugmakers, Fauci hinted that he anticipates more funding down the line.

"Nothing convinces the source of resources to give more resources than success," he said. "If we come up with success, I think we'll get more."

Pandemic 2.0

Switching gears, Morrison noted that the current phase of the pandemic has stirred up anxieties once more, but also increased the pressure on Americans to get vaccinated against COVID-19 and to begin wearing masks again.

Asked whether he was hopeful that the U.S. could narrow the gap on vaccination and begin to curb the pandemic's spread, Fauci shared his predictions, with the caveat that he can't guarantee they will be right: "Since an acceleration of vaccines doesn't give a result until several weeks after, we are already on a trajectory that looks strikingly similar to the sharp incline that the U.K. saw," he said.

Average daily cases of COVID-19 ranged from 12,000 to 15,000 in the U.S. a little over a month ago, but now surpass 70,000, he noted. "We are going to be between 100,000 and 200,000 cases before this thing starts to turn around."

A lot depends on people's willingness to act quickly and get their shot, Fauci said, noting that 93 million eligible people remain unvaccinated.

Three states account for roughly 40% of the infections in the country, with Florida alone seeing 20% of new COVID cases nationwide, but Fauci said he's hopeful that even in those hotspots, things are changing.

"Where you're seeing a lot of infection, the rate of vaccination as an average is better than the rest of the country," he said. "That's telling us that the states that are suffering most from the increase are starting to realize that you've got to get vaccinated if you want to get out of this."

Fauci praised Republican governors and a member of Congress for their work in promoting vaccination. Arkansas Gov. Asa Hutchinson (R) is "out beating the bushes, asking people to get vaccinated," he said. Rep. Steve Scalise (R-La.) is telling people, "'Go out and get vaccinated,'" added Fauci, and we even have Florida Gov. Ron DeSantis (R), "who doesn't want to have mask mandates, going out, saying people should wind up getting vaccinated."

"I think we're going to see a turnaround," Fauci said.

Another "game changer," he said, would be when the COVID-19 vaccines switch from emergency use authorization to a standard approval.

Fauci said he believes that as soon as FDA grants full approval, "those people who are hesitant to get vaccinated because they perceive the emergency use authorization as not being proof enough that it's safe and effective -- even though we have ample, ample evidence that it's highly effective and highly safe -- I think you're going to see more people get vaccinated."

Standard approval would likely lead to the implementation of more local vaccination mandates as well, he said.

"You're not going to see a central mandate coming from the federal government, but you're going to see more universities, colleges, places of business -- once they get the cover of an officially approved vaccine -- they're going to start mandating vaccines. So, we're going to see an increase in vaccines, and that's going to be the solution to the problem."

https://www.medpagetoday.com/infectiousdisease/covid19vaccine/93896

Anti-VEGF Injections Preserved Vision in Severe Diabetic Retinopathy

 Intravitreal injections of a vascular endothelial growth factor (VEGF) inhibitor reduced disease severity and vision-threatening complications in patients with severe nonproliferative diabetic retinopathy (NPDR), the phase III PANORAMA trial found.

After 1 year of treatment with aflibercept (Eylea), approximately 80% of patients who received a more intensive dosing regimen saw a two-step or greater improvement in the Diabetic Retinopathy Severity Scale (DRSS) compared with only 15% of patients who received sham injections (adjusted difference 64.8%, 95% CI 55.8-73.9%, P<0.001), according to Charles Wykoff, MD, PhD, of Retina Consultants of Texas in Houston, and colleagues.

As reported in JAMA Ophthalmology, 65% of patients who received a less intensive dosing regimen showed the same improvement on the DRSS at week 52 (adjusted difference 50.1%, 95% CI 40.1-60.1%, P<0.001).

And at approximately 2 years of follow-up, only 18.7% of patients in the more intensive aflibercept group and 16.3% in the less intensive group developed vision-threatening complications or center-involving diabetic macular edema (CI-DME) versus 50% of the control group (P<0.001).

The trial found no differences in visual acuity among the groups at week 100. But in a post hoc analysis exclusively looking at participants with vision-threatening complications and/or CI-DME, about 29% on sham treatments lost five or more letters on the Early Treatment Diabetic Retinopathy Study chart at some point during the study versus only 9% of either treatment group.

Current diabetic retinopathy treatment guidelines are predominantly reactive, with treatment only recommended when CI-DME and/or proliferative diabetic retinopathy (PDR) develop, Wykoff's group highlighted.

"However, once PDR has developed, retinal damage from fibrosis and contraction may not be reversible, even with intervention, and can be associated with permanent vision loss," they wrote. "Subsequent treatment with [panretinal photocoagulation] leads to visual field loss because the procedure is inherently destructive. Therefore, prevention of progression to PDR and DME represents an important public health goal."

They also noted that the current standard of case for NPDR is simply observation, but pointed out that "the risk of patients with severe NPDR developing potentially irreversible PDR and associated vision loss (approximately 30% at 2 years in the control group of PANORAMA) suggests that implementing anti-VEGF therapy should be considered and discussed with these patients."

Based on this trial, the FDA approved Eylea in May 2019 indicated to treat all stages of diabetic retinopathy and diabetic macular edema. The VEGF inhibitor, which works by blocking the growth of new blood vessels and decreasing vascular permeability, also holds indications for neovascular age-related macular degeneration and macular edema following retinal vein occlusion. For diabetic retinopathy, the recommended dose is 2 mg (0.05 mL) of intravitreal injection every 4 weeks for the first five injections followed by 2 mg via intravitreal injection once every 8 weeks (the more intensive dosing regimen in PANORAMA).

The double-blind, 87-site trial included 402 patients with diabetes and severe treatment-naive NPDR -- defined as a DRSS level of 47 or 53. Participants were free of DME and had a best-corrected visual acuity of 20/40 or better. The cohort's average age was 56 years, 56% were male, and 77% were white.

Participants were randomized to one of three groups. The first group -- less intensive regimen -- received 2 mg of intravitreal aflibercept injections every 16 weeks after three initial monthly doses and one 8-week interval. The second group -- the more intensive regimen -- received 2 mg of intravitreal aflibercept injections every 8 weeks after five initial monthly doses during the first year, with flexible as-needed dosing in the second year if the investigator determined the DRSS level was worse than 35. The third group received sham injections with observation.

The primary endpoint was the proportion of eyes with a two-step or greater improvement in DRSS level from baseline to weeks 24 and 52. Secondary endpoints included the proportion of eyes that developed vision-threatening complications or CI-DME at weeks 52 and 100. Only one eye per participant was measured.

Outcomes for study participants worsened in the second year while on the as-needed dosing, Wykoff's group reported. Participants averaged just 1.8 injections during that year (with a maximum of 6 injections), and those with improvements in the DRSS dropped from 80% to 50%, while the incidence of vision-threatening complications increased.

Although no new safety signals emerged, the most common ocular adverse events -- occurring in 7.5% of eyes in any trial arm -- included conjunctival hemorrhage, DME, vitreous floaters, and eye pain. There were no cases of endophthalmitis reported.

"Thus, although 1 year of aflibercept therapy substantially decreased the occurrence of PDR and CI-DME compared with sham treatment and observation in the PANORAMA study, discontinuation or reduction in the frequency of therapy may lead to PDR-related complications," they wrote.

One important study limitation was the restriction to patients with severe to moderately severe NPDR, the researchers said, adding that it would've been useful to know how eyes with more or less severe retinopathy responded differently to the therapy.

In addition, the as-needed dosing in the second year precluded the ability to determine if continued regular dosing during that time would have been beneficial. Finally, trial participants were evaluated with more frequent visits than are typical in a clinical setting.

Disclosures

The study was funded by Regeneron Pharmaceuticals.

Wykoff reported numerous relationships with industry, including Regeneron. Some co-authors were employed by Regeneron and others disclosed various relationships with industry.

Primary Source

JAMA Ophthalmology

Source Reference: Brown DM, et al "Evaluation of intravitreal aflibercept for the treatment of severe nonproliferative diabetic retinopathy: Results from the PANORAMA randomized clinical trial" JAMA Ophthalmol 2021; DOI: 10.1001/jamaophthalmol.2021.2809.

https://www.medpagetoday.com/ophthalmology/generalophthalmology/93910

Therapeutic Solutions Gets FDA OK to Initiate Phase III for Universal Donor COVID Therapy

 Adult Stem Cell Therapy Previously Demonstrated to Block Inflammation While Regenerating Injured Tissue to Enter Final Phase of Testing

Therapeutic Solutions International, Inc., (OTC Markets: TSOI), announced today clearance from the Food and Drug Administration (FDA) to initiate a Phase III pivotal trial for registration of the Company's JadiCell™ universal donor stem cell as a treatment for COVID-19 associated lung failure.

In previous studies the Company has demonstrated the superior activity of JadiCell™ to other types of stem cells including bone marrow, adipose, cord blood, and placenta. Furthermore, the JadiCell™ was shown to be 100% effective in saving the lives of COVID-19 patients under the age of 85 in a double-blind placebo controlled clinical trial with patients in the ICU on a ventilator. In patients over the age of 85 the survival rate was 91%1.

"We are thankful for the strong regulatory, basic research and translational team that has worked in successfully obtaining this FDA clearance," said Dr. Thomas E. Ichim, Director of the Company. "FDA clearance to initiate a Phase III clinical trial means we are at the last phase of development before commercially selling the product. This positions us in a highly exclusive place in that to our knowledge no other cells have this potent ability to concurrently suppress inflammation while restoring function of tissue damaged by SAR-CoV-2."

https://finance.yahoo.com/news/therapeutic-solutions-international-receives-fda-130000153.html

White House Defies WHO With Plans To Start Doling Out Booster Shots

 Despite WHO Director-General Dr. Tedros's pleas for the west to impose a booster shot "moratorium" to give the developing world a better chance of catching up to North America and Europe in the vaccination race, it looks like President Biden is preparing to greenlight booster jabs for the most vulnerable, Axios reports.

Citing anonymous sources, Axios says Biden and his team are "actively working toward" allowing the highest-risk patients to receive a third jab, a policy that could be handed down in the coming days or weeks, despite the WHO's pleas. The recommendation is likely to be issued "soon", according to Axios's sources.

Israel became the first country to start handing out booster shots earlier this month, and the UK and Germany are already reportedly drawing up plans for booster jabs as well. According to Axios, some immunocompromised people see a much bigger benefit from the third dose.

Of course, approval for the third dose will need to come from the FDA, and Biden Administration officials are working with the agency to try and work something out. But as Axios points out, scientists aren't exactly in agreement that booster shots are the right course of action. Some are concerned that antibodies from the shots fade over time.

"We...are prepared if the FDA decides that they are going to recommend a booster," White House Press Secretary Jen Psaki said yesterday at a briefing.

"That is why we ordered the number of doses we did order several months ago, because we are like Boy Scouts and Girl Scouts and always want to be prepared."

The FDA recently claimed there wasn't enough evidence to warrant recommending booster shots after Pfizer started actively campaigning for them. But apparently, they have changed their tune, even as more data emerges to suggest that the present delta-driven wave of infections might soon start to wane.

Moderna CEO Stephane Bancel appeared on CNBC Thursday morning to advocate the need for booster shots while promoting the latest favorable data (trial data showing the Moderna jab is 93% effective).

The US isn't the only western power ignoring the WHO's call for the moratorium: France on Thursday announced that it would start doling out booster jabs in the fall, joining Germany in the UK, who have announced similar plans.

https://www.zerohedge.com/political/white-house-defies-who-plans-start-doling-out-booster-shots

Amedisys reports earning, says pandemic affecting hospice segment

 Amedisys Inc. on Wednesday reported second-quarter net income of $80.1 million, or $1.69 per share, as the company said its hospice segment fell short of expectations due to hiring difficulties caused by the COVID pandemic.

That’s up from $34.7 million in earnings, or $1.34 per share, during the second quarter of 2020.

Earnings, adjusted for non-recurring costs were $2.43 per share.

The results topped Wall Street expectations. The average estimate of seven analysts surveyed by Zacks Investment Research was for earnings of $1.64 per share.

The Baton Rouge-based home health care and hospice services provider posted revenue of $564.2 million in the period, missing Street forecasts. Six analysts surveyed by Zacks expected $564.7 million.

Amedisys said it completed the previously announced purchase of Contessa Health, a Nashville-based health technology startup, which will allow the company to take care of more complex patients in their homes.

The company announced it expanded its credit facility, giving Amedisys access to $1 billion via a term loan and revolver. This is a sign the company plans to do more acquisitions, said Paul Kusserow, chairman and chief executive officer.

The Amedisys board of directors has approved a $100 million stock buy-back program, which will be used opportunistically, Kusserow said.

Amedisys expects full-year earnings in the range of $6.03 to $6.18 per share, with revenue in the range of $2.24 billion to $2.26 billion. The company revised the forecast, based on the hospice segment's performance. The problem is due to hiring and employee turnover issues caused by the pandemic.

“With our recent acquisition activity, we believe that there is a significant opportunity to grow our hospice segment, which has required us to invest in leadership and continue to hire clinical employees to support this future growth,” the company said.

https://www.theadvocate.com/baton_rouge/news/business/article_bff6fb7a-f56d-11eb-9b68-9717ea277651.html