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Friday, October 8, 2021

FDA seals Chemocentryx’s fate

 Chemocentryx finally got the green light today for Tavneos in ANCA-associated vasculitis after a Pdufa delay, and the thumbs up follows previous precedent in that Pdufa date extensions rarely result in knockbacks. While the news sent Chemocentry’x shares soaring 64% the reaction is still not enough to put the company to levels seen before the mixed adcom in May, when shares lost three quarters of their value. The FDA’s concerns over liver toxicity seem to have been abated with the use of frequent liver function tests, and Tavneos's label comes without a black box warning. Tavneos, a complement C5a inhibitor, has been pegged as a pipeline in a product, but has suffered mid-stage setbacks in hidradenitis suppurativa and glomerulonephritis, thus leaving vasculitis as its main source of revenue.

Chemocentry'x pipeline
ProductMechanism of actionIndication/status2026e sales ($m)
Tavneos (avacopan)Complement factor C5a inhibitorVasculitis (approved in US and Japan, EU decision by end of 2021)610
Hidradenitis suppurativa (Aurora Ph2 failed), plan for Ph3 in severe patients57
Glomerulonephritis (Accolade Ph2 failed), discussing path forward with FDA41
Lupus nephritis study planned to start H1 2022-
CCX140CCR2 inhibitorDiabetic kidney disease (Ph2), development in focal segmental glomerulosclerosis discontinued-
CCX507CCR9 inhibitorUlcerative colitis (Ph1)-
CCX559PD-L1 inhibitorSolid tumours (Ph1), oral-
CCX587CCR6 inhibitorTh17-mediated inflammation (psoriasis; preclinical)-
Source: company releases & Evaluate Pharma.

https://www.evaluate.com/vantage/articles/news/snippets/fda-seals-chemocentryxs-fate

School hiring decline, worker shortages curb U.S. job growth

 The U.S. economy created the fewest jobs in nine months in September amid a drop in hiring at schools and worker shortages, but ebbing COVID-19 cases and the end of generous unemployment benefits could boost employment gains in the months ahead.

Though the Labor Department's closely watched employment report on Friday showed the unemployment rate dropping to an 18-month low of 4.8%, that was in part due to people leaving the labor force. But there were signs of labor market tightness. Wage gains accelerated further, permanent job losses decreased and fewer people were experiencing long spells of unemployment.

"The biggest problem is not that growth has slowed, it is that people are still scared to go back to work," said Brad McMillan, chief investment officer for Commonwealth Financial Network.

The survey of establishments showed nonfarm payrolls increased by 194,000 jobs last month. Data for August was revised to show 366,000 jobs created instead of the previously reported 235,000 positions. Employment is 5.0 million jobs below its peak in February 2020.

Economists polled by Reuters had forecast payrolls would increase by 500,000 jobs, with estimates ranging from as high as 700,000 jobs to as low as 250,000. The unemployment rate of 4.8% was down four-tenths of percentage point from August, while average hourly earnings increased 0.6% from 0.4% in August. The average workweek also lengthened by 0.2 hours to 34.8 hours.

Employment gains were restrained by a drop of 161,000 in state and local government payrolls. Private education jobs fell by 19,000. Most back-to-school hiring typically occurs in September, but recruitment last month was lower than usual, resulting in a decline after stripping seasonal fluctuations from the data. Pandemic-related staffing fluctuations in education have distorted the normal seasonal patterns, making it difficult to interpret the data, the government said.

The drop in public education jobs led to a decrease of 123,000 in government employment. That was offset by an increase of 317,000 in private payrolls.

Employment in leisure and hospitality rose by 74,000 in September, with hiring at restaurants and bars rising 29,000. There were also gains in professional and business services payrolls. Retailers hired 56,000 workers, while manufacturers added 26,000 jobs. Construction payrolls rose by 22,000 jobs.

With wage inflation rising, September's meager payroll gains probably will not deter the Federal Reserve https://www.reuters.com/business/fed-closes-november-bond-taper-after-jobs-report-2021-10-08 from beginning to scale back its massive monthly bond-buying program this year.

The U.S. central bank signaled last month that it could start tapering its asset purchases as soon as November. Economists expect that announcement will come at the Nov. 2-3 policy meeting.

"The bar was always quite low for a tapering of asset purchases to be announced in November and the combination of upward revisions, the drop in the unemployment rate, and signs of labor market tightness should more than meet it," said Andrew Hollenhorst, chief U.S. economist at Citigroup in New York.

The likelihood of a taper was bolstered by the U.S. Senate agreeing on Thursday to raise the Treasury Department's borrowing authority until December.

Stocks on Wall Street were mixed in choppy trade. The dollar slipped against a basket of currencies. U.S. Treasury prices fell.

MIXED SIGNALS

Despite the modest jobs gain, accelerating wage growth bodes well for the economic outlook, following an apparent sharp slowdown in growth in the third quarter.

The economy hit a speed bump last quarter because of the summer flare-up in coronavirus cases, an ebb in the flow of pandemic relief money from the government, scarce labor and raw materials, which have hammered motor vehicle sales.

The Atlanta Fed estimates that gross domestic product growth braked to a 1.3% annualized rate in the July-September quarter. The economy grew at a 6.7% pace in the second quarter.

But with COVID-19 infections decreasing and schools fully reopened for in-person learning, more people should be able to rejoin the labor force. In the months ahead, the labor squeeze could ease following the expiration of federal government-funded benefits in early September.

These expanded benefits were blamed by businesses and Republicans for the failure to fill a record 10.9 million job openings as of the end of July. So far, many of the unemployed appear to be in no hurry to start looking for jobs, having saved a chunk of their government money.

The smaller household survey from which the unemployment rate is derived showed 183,000 people left the labor force in September. As result, the labor force participation rate, or the proportion of working-age Americans who have a job or are looking for one, dipped to 61.6% from 61.7% in August.

Some economists say a significant portion of people who dropped out of the labor force have retired, thanks to a strong stock market and record house price gains, which boosted household wealth. Self employment has also increased.

"Labor supply remains an important constraint and an issue that may very well not get resolved in a short time horizon," said Ellen Zentner, chief U.S. economist at Morgan Stanley in New York.

Even though participation remains low, some aspects of the labor market are improving. The employment-to-population ratio, viewed as a measure of an economy's ability to create employment, rose to 58.7% from 58.5 in August.

The number of long-term unemployed dropped by 496,000 to 2.7 million in September. They accounted for 34.5% of the 7.7 million officially unemployed people, down from 37.4% in August. The median duration of unemployment fell to 13.3 weeks from 14.7 weeks in August.

https://www.yahoo.com/news/u-job-growth-seen-picking-040316433.html

Nkarta Expects Initial Data From CAR NK Cell Therapy In Blood Cancer In 2022

 

  • Nkarta Inc (NASDAQ: NKTX) has updated guidance on initial data readout of Phase 1 trial of NKX101 in relapsed or refractory acute myeloid leukemia or higher-risk myelodysplastic syndromes.

  • Data from the engineered CAR NK cell therapy candidate targeting the NKG2D ligand is expected in 1H of 2022, against the end of 2021 expected earlier.

  • Multiple factors have affected the cadence of the NKX101 Phase 1 study, including the use of haplomatched (half-matched or partially-matched) donor-derived cells, the requirement for a staggered enrollment of patients that was longer than expected initially, and COVID-19 related disruptions.

  • Additionally, Nkarta dosed the first patient in Phase 1 trial of NKX019 in advanced B-cell malignancies.

  • NKX019 is an NK cell immunotherapy engineered to eradicate tumors expressing CD19, a validated B-cell cancer target.

Cellectis cut to Neutral from Outperform by Baird

 Target to $10 from $39

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

Takeda transplant drug gets unanimous support of FDA AdComm

 Takeda’s faltering effort to deliver a wave of new products that will drive sales growth over the next decade has received a boost. Having seen its other prospects stumble in recent months, Takeda got back on track with unanimous FDA advisory committee votes in favor of a transplant drug.

The drug, maribavir, beat standard of care in transplant recipients with refractory cytomegalovirus (CMV) infection in an open-label phase 3 clinical trial. With the study also linking maribavir to fewer treatment-related toxicities such as low white blood cell counts and acute kidney injury, Takeda went into the advisory committee meeting holding a strong hand.

Takeda was rewarded with unanimous votes in favor of maribavir on the two key questions. All of the experts agreed the overall benefit-risk assessment of maribavir is favorable, regardless of whether a patient is resistant to the existing treatment options. 

“Overall, the data are very persuasive in support of approval,” Nancy Bridges, M.D., transplantation branch chief of the National Institute of Allergy and Infectious Diseases, said at the committee meeting. 

The unanimous votes suggest Takeda is on track to win FDA approval for maribavir. However, the experts also identified concerns with the design of the clinical trial, including the patient population and the open-label nature of the study. 

Arthur Flatau, M.D., the patient representative, and Lauren Lee, M.D., bone marrow transplant medical director at Brooke Army Medical Center, both flagged the lack of data in children as a gap in the evidence that needs to be addressed. Bridges identified another shortcoming of the composition of the study population.

“The study participants were overwhelmingly white,” Bridges said. “We know that CMV serum positivity has a much higher prevalence among African Americans. So, within the context that I do hope that this drug is approved, I would like to see some requests to the company to gather data about efficacy in African Americans, because I don't think we have any data really on that.”

Lee also expressed an interest in seeing how maribavir would fare in a blinded, controlled clinical trial. Maribavir, back when it was owned by ViroPharma, failed a phase 3 placebo-controlled clinical trial in 2009. Takeda, which acquired maribavir through its takeover of Shire, defended its decision to run an open-label study on the grounds that the drug causes taste disturbance that affects blinding. 

https://www.fiercebiotech.com/biotech/takeda-s-transplant-drug-gets-unanimous-support-fda-adcomm-despite-concerns-over-diversity

Flu shots, Moderna COVID-19 booster can be given at same doctor visit: Sanofi study

 With the arrival of autumn and warnings of a potential “twindemic,” many are prioritizing vaccinations with more urgency this year.

Thursday, Sanofi provided timely data that show elderly people can take care of their COVID-19 booster and flu inoculation needs in one stop.

Interim results from co-administration of Sanofi’s Fluzone high-dose quadrivalent vaccine and a Moderna COVID-19 booster in the same doctor’s visit show that both provide similar immunogenicity responses—in addition to comparable safety and tolerability profiles—to when they are provided individually.  

The study, conducted in the U.S., includes approximately 300 participants age 65 and older who are eligible for the high-dose version of Fluzone and received the Moderna COVID-19 vaccine at least five months prior to enrollment. An application by Moderna for use of its shot as a booster is under review by the FDA.

The results reinforce co-administration recommendations in several countries including the U.S., Germany, France and the U.K., Sanofi says. 

A similar co-administration trial for another vaccine, conducted earlier this year by Pfizer, produced comparable results. In that study of 1,727 people at 66 sites, Pfizer tested its Prevnar 20 pneumococcal shot, which was approved in June, alongside an unnamed flu shot. The co-administered vaccines provided the same protection, along with similar safety and tolerability profiles, compared to when they were provided a month apart.  

The company also is running a trial where Prevnar 20 is co-administered with its mRNA COVID-19 vaccine.

The Sanofi results come less than two weeks after the company revealed positive data for a clinical trial of its own mRNA coronavirus vaccine, while at the same time saying it was abandoning the effort. Sanofi said it saw no reason to bring another mRNA COVID-19 shot to the market so late but that the findings will allow it to shift gears and pursue vaccines for other pathogens.

https://www.fiercepharma.com/pharma/trial-shows-sanofi-s-fluzone-and-moderna-s-covid-19-shot-perform-same-when-given-same-doctor

Merck molnupiravir: blockbuster during pandemic; what about endemic COVID-19?

 After showing a 50% reduction in the risk of hospitalization or death, Merck & Co. and Ridgeback Biotherapeutics’ molnupiravir looks on track to secure an FDA emergency use authorization and become a blockbuster earner during the pandemic. But what kind of longer-term market will the drug face once COVID-19 makes the likely shift from pandemic to endemic?

With the increasing number of people vaccinated, COVID-19 is gradually becoming more manageable. Once the public health crisis transitions to the endemic stage, the need for treatment will persist. That will leave a $6 billion global market for oral antivirals, Bernstein analyst Ronny Gal estimates.

Gal used the influenza market as the benchmark for his calculation and incorporated efficacy data from molnupiravir and COVID-19 vaccines. He now projects Merck—as the only company with positive clinical data—will take half of the endemic oral drug market, with Pfizer and Roche potentially sharing the rest if their contenders prove successful.

Molnupiravir’s 50% reduction in hospitalization and death risk came from the MOVe-OUT study in high-risk, unvaccinated adults. That profile description only matches about 15% of the U.S. population, Gal noted. Merck may argue that vaccinated, high-risk patients should also be eligible for molnupiravir, but, given the impressive protection already offered by the vaccine, the drug will have a hard time making that case, Gal said.

However, Pfizer and Roche are running their trials differently, which could open up a broader market for oral antivirals. Pfizer has two studies for PF-07321332, used in combo with AbbVie’s HIV antiviral Norvir. One is similar to MOVe-OUT in high-risk patients to measure reduction in hospitalization or death. The other is in low-risk patients and evaluates alleviation of COVID symptoms as the primary endpoint. By comparison, Roche’s Atea Pharmaceuticals-partnered AT-527 is in phase 3 testing in a broader non-hospitalized population regardless of risk factors, and it’s also using improvement of symptoms as the primary goal.

Using Roche’s newer influenza drug Xofluza as an example, Gal suggested that Pfizer and Roche's symptom alleviation trials have a relatively low efficacy bar to cross and gain approval.

Because vaccination have already significantly lowered hospitalization rate, “we believe the oral antivirals will be used broadly based on symptom alleviation and shortening of disease durations,” Gal wrote in an investor note Wednesday.

In the U.S., influenza causes about 10 million to 15 million medical visits each year, accounting for about 30% of symptomatic cases, and about 80% of them eventually get a script for an antiviral, mostly Roche’s Tamiflu or its generic.

All told, Gal assumed a slightly higher penetration of treatment for COVID than influenza, estimating 40% of all symptomatic COVID infections will be treated with an oral antiviral.

Then the question is the overall number of diagnosed cases. Compared with the high, 90% effectiveness of COVID vaccines, influenza vaccines are much less effective at 40% or below and are adopted less. But the coronavirus is much more infective than influenza. Taking these factors together, Gal’s team figures there would be about 60% as many COVID infections a year as there are flu infections. So that would translate into about 18 million overall COVID cases in the U.S. each year.

In terms of pricing, Merck already has a deal with the Biden administration to supply 1.7 million courses of molnupiravir to the U.S. government for $1.2 billion. That’s about $700 per course. Merck said it expects to make 10 million courses of the drug by the end of 2021, meaning $7 billion in revenue.

Even though that’s the pandemic price before the data readout, Gal argued that the sticker will likely be kept same for the postpandemic world. As for Roche and Pfizer, Gal expected they will adopt a lower, $300-per-treatment price for their drugs, given they could have broader labels. It would still be a nice price; Xofluza costs about $150 after showing about a one-day improvement in time to symptom relief, Gal noted.

All told, Gal estimates a $6 billion global market for oral antivirals beginning in 2023. Of those, Merck could take away $3 billion, and Roche and Pfizer will split the remainder. Gal assigned the two latecomers lower market share at the moment after adjusting for the risks of failure.

https://www.fiercepharma.com/pharma/merck-molnupiravir-blockbuster-covid-19-pandemic-endemic-oral-antivirals-market