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FDA adcomm votes in favor of Alnylam’s new indication for Onpattro
The FDA’s Cardiovascular and Renal Drugs Advisory Committee on Wednesday voted 9-3 in favor of Alnylam Pharmaceuticals’ Onpattro (patisiran) on whether…
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The FDA’s Cardiovascular and Renal Drugs Advisory Committee on Wednesday voted 9-3 in favor of Alnylam Pharmaceuticals’ Onpattro (patisiran) on whether its benefits outweigh its risks for the treatment of ATTR cardiomyopathy.
Panelists agreed that the magnitude of Onpattro’s benefit in this indication was small, but the risks were even smaller.
Adcomm member Edward Kasper of Johns Hopkins School of Medicine said he based his “yes” vote on the fact there’s a “light wind” for benefit and “no wind” for risk. David Cella, professor at Northwestern University Feinberg School of Medicine, also voted in favor and noted limited benefits but said that he hopes clinicians will counsel patients on this option.
Alnylam touted the results of the pivotal trial for Onpattro, which first won approval in 2018 as a treatment of peripheral nerve disease caused by hereditary transthyretin-mediated amyloidosis (hATTR), as the treatment showed statistical significance with the primary endpoint, which was the change from baseline at month 12 in a 6-minute walk test, and a secondary endpoint on the change in baseline on the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS).
But ahead of the meeting and throughout its presentations Wednesday, the FDA raised questions on the effect size of siRNA-based Onpattro, which is an injection given every three weeks, and whether the positive effects are actually clinically meaningful. If approved in this indication, Onpattro would have to compete with Pfizer’s Vyndamax (tafamidis) capsules, which FDA approved in 2019 as the first treatment for ATTR-CM.
“While the results from the APOLLO-B study statistically favor patisiran over placebo, the magnitude of the treatment effect on function and quality of life is small and may not be clinically meaningful,” the FDA said in briefing documents ahead of the meeting. The agency also made clear at the meeting that the trial did not show a benefit to mortality or irreversible morbidity.
On the question of the clinical meaningfulness of Onpattro, Cella said that the primary endpoint “was met with a very small number,” and “just comparing this number to the literature it’s quite small and that’s a big part about why we’re having this meeting.”
Panelist Christopher O’Connor, president and executive director of the Virginia-based Inova Heart and Vascular Institute, said he thought the magnitude of the treatment’s effect “feels small and low but the clinical meaningfulness is unclear,” as he noted “significant design flaws” in Alnylam’s pivotal trial.
Panelist David Moliterno, professor of internal medicine at University of Kentucky Medical Center, who called his “yes” vote a “bunt single,” to a use a baseball metaphor, and similarly called the treatment benefit “small,” and noted that in Black and other non-Caucasian subpopulations, as well as women, the benefits from the trial looked even smaller. He said he’d be concerned if tafamidis gets “put on the side shelf” in favor of Onpattro.
The panelists all seemed to agree that the tafamidis interaction with Onpattro “was of concern,” according to the panel’s chair Javed Butler of the University of Mississippi, who voted against the benefit-risk profile of Onpattro, and he noted the panel was struggling to understand which patient populations might benefit of those who are progressing on tafamidis.
“I struggled with the vote,” Butler said. “I didn’t know if the benefits were clinically meaningful.”
But the panelists didn’t seem to go as far as the FDA did in questioning the use of the KCCQ-OSS, which noted on one of its slides:
There were neither appropriate anchor scales administered, nor qualitative data collected to aid in the evaluation of the clinical meaningfulness of the treatment effects of 6MWT or KCCQ-OSS, from the perspective of patients.
Panelist Noel Bairey Merz, a professor of cardiology at Cedars-Sinai Medical Center who voted against Onpattro in this indication, noted that after listening to the patients in the open public forum of the adcomm meeting, which she found “enlightening,” the 6MWT may not have been optimal in this case.
“I did not feel like there was benefit,” Bairey Merz said. “It was upset not by risks but by potential harm. Opting out of one formulation for another that may not be perceived as better is a potential harm.”
Ravi Thadhani, the EVP for health affairs at Emory University who voted in favor of Onpattro in ATTR-CM, said the benefit outweighed the risks and, regarding the clinical meaningfulness, “we know it’s minimal,” and “I would urge discussions between the agency and sponsor” on the subpopulations who did not benefit from Onpattro.
treatment fda
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One city held a mass passport-getting event
A New Orleans congressman organized a way for people to apply for their passports en masse.
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While the number of Americans who do not have a passport has dropped steadily from more than 80% in 1990 to just over 50% now, a lack of knowledge around passport requirements still keeps a significant portion of the population away from international travel.
Over the four years that passed since the start of covid-19, passport offices have also been dealing with significant backlog due to the high numbers of people who were looking to get a passport post-pandemic.
Related: Here is why it is (still) taking forever to get a passport
To deal with these concurrent issues, the U.S. State Department recently held a mass passport-getting event in the city of New Orleans. Called the "Passport Acceptance Event," the gathering was held at a local auditorium and invited residents of Louisiana’s 2nd Congressional District to complete a passport application on-site with the help of staff and government workers.
'Come apply for your passport, no appointment is required'
"Hey #LA02," Rep. Troy A. Carter Sr. (D-LA), whose office co-hosted the event alongside the city of New Orleans, wrote to his followers on Instagram (META) . "My office is providing passport services at our #PassportAcceptance event. Come apply for your passport, no appointment is required."
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The event was held on March 14 from 10 a.m. to 1 p.m. While it was designed for those who are already eligible for U.S. citizenship rather than as a way to help non-citizens with immigration questions, it helped those completing the application for the first time fill out forms and make sure they have the photographs and identity documents they need. The passport offices in New Orleans where one would normally have to bring already-completed forms have also been dealing with lines and would require one to book spots weeks in advance.
These are the countries with the highest-ranking passports in 2024
According to Carter Sr.'s communications team, those who submitted their passport application at the event also received expedited processing of two to three weeks (according to the State Department's website, times for regular processing are currently six to eight weeks).
While Carter Sr.'s office has not released the numbers of people who applied for a passport on March 14, photos from the event show that many took advantage of the opportunity to apply for a passport in a group setting and get expedited processing.
Every couple of months, a new ranking agency puts together a list of the most and least powerful passports in the world based on factors such as visa-free travel and opportunities for cross-border business.
In January, global citizenship and financial advisory firm Arton Capital identified United Arab Emirates as having the most powerful passport in 2024. While the United States topped the list of one such ranking in 2014, worsening relations with a number of countries as well as stricter immigration rules even as other countries have taken strides to create opportunities for investors and digital nomads caused the American passport to slip in recent years.
A UAE passport grants holders visa-free or visa-on-arrival access to 180 of the world’s 198 countries (this calculation includes disputed territories such as Kosovo and Western Sahara) while Americans currently have the same access to 151 countries.
stocks pandemic covid-19 grantsUncategorized
Fast-food chain closes restaurants after Chapter 11 bankruptcy
Several major fast-food chains recently have struggled to keep restaurants open.
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Competition in the fast-food space has been brutal as operators deal with inflation, consumers who are worried about the economy and their jobs and, in recent months, the falling cost of eating at home.
Add in that many fast-food chains took on more debt during the covid pandemic and that labor costs are rising, and you have a perfect storm of problems.
It's a situation where Restaurant Brands International (QSR) has suffered as much as any company.
Related: Wendy's menu drops a fan favorite item, adds something new
Three major Burger King franchise operators filed for bankruptcy in 2023, and the chain saw hundreds of stores close. It also saw multiple Popeyes franchisees move into bankruptcy, with dozens of locations closing.
RBI also stepped in and purchased one of its key franchisees.
"Carrols is the largest Burger King franchisee in the United States today, operating 1,022 Burger King restaurants in 23 states that generated approximately $1.8 billion of system sales during the 12 months ended Sept. 30, 2023," RBI said in a news release. Carrols also owns and operates 60 Popeyes restaurants in six states."
The multichain company made the move after two of its large franchisees, Premier Kings and Meridian, saw multiple locations not purchased when they reached auction after Chapter 11 bankruptcy filings. In that case, RBI bought select locations but allowed others to close.
Image source: Chen Jianli/Xinhua via Getty
Another fast-food chain faces bankruptcy problems
Bojangles may not be as big a name as Burger King or Popeye's, but it's a popular chain with more than 800 restaurants in eight states.
"Bojangles is a Carolina-born restaurant chain specializing in craveable Southern chicken, biscuits and tea made fresh daily from real recipes, and with a friendly smile," the chain says on its website. "Founded in 1977 as a single location in Charlotte, our beloved brand continues to grow nationwide."
Like RBI, Bojangles uses a franchise model, which makes it dependent on the financial health of its operators. The company ultimately saw all its Maryland locations close due to the financial situation of one of its franchisees.
Unlike. RBI, Bojangles is not public — it was taken private by Durational Capital Management LP and Jordan Co. in 2018 — which means the company does not disclose its financial information to the public.
That makes it hard to know whether overall softness for the brand contributed to the chain seeing its five Maryland locations after a Chapter 11 bankruptcy filing.
Bojangles has a messy bankruptcy situation
Even though the locations still appear on the Bojangles website, they have been shuttered since late 2023. The locations were operated by Salim Kakakhail and Yavir Akbar Durranni. The partners operated under a variety of LLCs, including ABS Network, according to local news channel WUSA9.
The station reported that the owners face a state investigation over complaints of wage theft and fraudulent W2s. In November Durranni and ABS Network filed for bankruptcy in New Jersey, WUSA9 reported.
"Not only do former employees say these men owe them money, WUSA9 learned the former owners owe the state, too, and have over $69,000 in back property taxes."
Former employees also say that the restaurant would regularly purchase fried chicken from Popeyes and Safeway when it ran out in their stores, the station reported.
Bojangles sent the station a comment on the situation.
"The franchisee is no longer in the Bojangles system," the company said. "However, it is important to note in your coverage that franchisees are independent business owners who are licensed to operate a brand but have autonomy over many aspects of their business, including hiring employees and payroll responsibilities."
Kakakhail and Durranni did not respond to multiple requests for comment from WUSA9.
bankruptcy pandemicUncategorized
Industrial Production Increased 0.1% in February
From the Fed: Industrial Production and Capacity Utilization
Industrial production edged up 0.1 percent in February after declining 0.5 percent in January. In February, the output of manufacturing rose 0.8 percent and the index for mining climbed 2.2 p…
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Industrial production edged up 0.1 percent in February after declining 0.5 percent in January. In February, the output of manufacturing rose 0.8 percent and the index for mining climbed 2.2 percent. Both gains partly reflected recoveries from weather-related declines in January. The index for utilities fell 7.5 percent in February because of warmer-than-typical temperatures. At 102.3 percent of its 2017 average, total industrial production in February was 0.2 percent below its year-earlier level. Capacity utilization for the industrial sector remained at 78.3 percent in February, a rate that is 1.3 percentage points below its long-run (1972–2023) average.Click on graph for larger image.
emphasis added
This graph shows Capacity Utilization. This series is up from the record low set in April 2020, and above the level in February 2020 (pre-pandemic).
Capacity utilization at 78.3% is 1.3% below the average from 1972 to 2022. This was below consensus expectations.
Note: y-axis doesn't start at zero to better show the change.
The second graph shows industrial production since 1967.Industrial production increased to 102.3. This is above the pre-pandemic level.
Industrial production was above consensus expectations.
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