Apellis eye drug succeeds in one key study, but falls short in its twin

 A closely watched experimental treatment for a leading cause of blindness slowed the death of retinal cells in a large, late-stage study, a finding that the drug's maker, Apellis Pharmaceuticals, said Thursday will support an application to the Food and Drug Administration for approval.

But results from a second, similarly sized clinical trial showed no significant benefit to treatment over a sham eye injection, raising questions about why two studies designed to be essentially identical produced divergent results. The split outcome could also make Apellis' case to regulators more difficult, inserting doubt into a development program that's viewed as critically important for the Waltham, Massachusetts-based biotech company.

The two Phase 3 studies, respectively dubbed OAKS and DERBY, tested monthly or every-other-month eye injections of Apellis' drug pegcetacoplan in 1,258 patients with geographic atrophy, a progressive and irreversible form of vision loss that develops from age-related macular degeneration, or AMD.

In OAKS, both treatment regimens reduced the growth of lesions in the retina significantly more than sham injections after one year of study. But in DERBY, neither did.

In an interview, Apellis CEO Cedric Francois emphasized the "totality of the data" support the use of treatment with pegcetacoplan. An analysis of the two Phase 3 studies combined, which Apellis had planned for beforehand, showed a significant difference between treatment and sham injection overall for both monthly and every-other-month dosing.

"Yes, we had a narrow miss in DERBY. But we have a highly statistically significant readout in OAKS, which is further supported by our Phase 2 clinical trial," said Francois, referring to a study that first read out results in 2017.

Apellis only released summary results from the two trials Thursday. More detailed data will be presented at a future medical meeting, the company said, and the studies will continue for another year to further assess other secondary measures, like the drug's impact on visual acuity and reading speed. Additional data, which Apellis is still evaluating, could help answer why the two trials produced conflicting results.

While there are several effective medicines for the "wet" form of advanced AMD, none are available for geographic atrophy, which affects approximately 1 million Americans, according to data cited by Apellis. The company believes pegcetacoplan can be the first, and now plans to submit an application for FDA approval in the first half of next year.

An approved treatment could mean much to people with the disease, who have nothing to slow the steady degradation of their vision. The death of retinal cells in the macula — responsible for central vision — typically results in a loss of ability to see clearly and to see colors, in addition to causing dark splotches in the eye's sight.

"Once these retinal cells have died, they cannot be revived," said Jeffrey Heier, an investigator in the Apellis trials and the director of retinal research at the Ophthalmic Consultants of Boston, in an email. "Therefore, the goal is to slow the progression of the disease. Even when central vision is already lost, there is benefit to preserving as much vision as possible."

Study results suggested a greater benefit to treatment in patients whose eye lesions were outside the fovea, a central region of the macula that's dense with photoreceptor cells. Slowing the growth of lesions into the fovea could potentially help preserve some core vision.

Importantly, treatment appeared to cause a lower-than-expected rate of a side effect involving leakage from retinal blood vessels. There were two confirmed, and one suspected, cases of a serious kind of infection in treated eyes, but no changes in vision were reported as a result.

"The safety profile is better than any of us had hoped for," said Francois.

Still, the negative result from DERBY muddies the positive finding in OAKS. Additionally, the percentage reduction in lesion growth versus sham injections in the latter trial — 22% for monthly injections and 16% for every other month — was lower than what Apellis reported in its smaller Phase 2 study.

An approval, should the FDA grant one, would greatly buoy Apellis, which earlier this year won its first drug OK for a systemically infused version of pegcetacoplan, now sold as Empaveli for the treatment of a rare blood disorder called paroxysmal nocturnal hemoglobinuria. As geographic atrophy affects many more people, investors and analysts on Wall Street expect the first treatment for the eye condition could earn its developer billions of dollars in sales.

The market reaction to the' data could also affect the broader biotech industry, which draws momentum from smaller companies like Apellis proving they can discover and develop new therapies. Writing in a note to clients earlier this week, Umer Raffat, an analyst at Evercore ISI, said the readout is "considered one of the biggest catalysts in entire biopharma this fall."

Several other companies, including Iveric Bio, NGM Biopharmaceuticals and Anexxon Biosciences, are also developing geographic atrophy treatments.

All three are following a similar scientific hypothesis as Apellis, which views geographic atrophy as the result of excessive activation of the complement system, an arm of the body's innate immune defenses.

Previous efforts to treat AMD by blocking complement activation have come up short, however, with several late-stage studies from Roche and Novartis delivering negative results.

The positive findings from OAKS, Apellis' Francois said, are both evidence of complement system's role in AMD and serve as a bridge to the company's broader ambitions to target complement in a wider range of eye, rare and neurological diseases.

"It is the first of many where we are going to see the therapeutic potential of controlling complement," he said.

https://www.biopharmadive.com/news/apellis-geographic-atrophy-study-results-pegcetacoplan/606278/

DHS to increase fines for mask violations in airports, on planes

 The Department of Homeland Security announced on Thursday that those who refuse or fail to wear a mask in airports, planes or certain other public transportation modes will be subject to higher fines.

Though fines previously started at $250 and ranged upward, the new fines, which will become effective on Friday, would start at $500. DHS said that first-time offenders could see a fine of between $500 and $1,000. Second-time offenders could be fined between $1,000 and $3,000.

Additionally, the department said that the federal mask mandate would remain effective until Jan. 18. It is a part of President Biden’s larger COVID-19 action plan, which was implemented to combat further spread of COVID-19 and avoid possible shutdowns that were experienced last year.

“If you break the rules, be prepared to pay. And by the way, show some respect," Biden said in remarks on Thursday.

“The anger you see on television toward flight attendants and others doing their job is wrong, it’s ugly,” he added.

The Federal Aviation Administration (FAA) has reported a number of instances where passengers have disregarded mask mandates, sometimes at the detriment of crew staff and passengers as employees try to handle unruly passengers.

One unruly passenger was fined $29,000 after she refused to wear a facial covering and shouted at the aircraft crew. The FAA also reported that the passenger punched a passenger in the face after the person raised complaints about being bumped by the unruly passenger.

The DHS noted that the fines levied by Transportation Security Administration (TSA) are separate from ones that are doled out by the FAA over unruly passenger behavior.

“We appreciate the majority of travelers each day who voluntarily follow the requirement, but find this action necessary to maximize the protections for those who use and work within the transportation system, and to contain COVID-19,” TSA Administrator David Pekoske said in a statement Thursday.

“By doubling the range of penalties, we seek to reinforce the importance of voluntary adherence,” he added.

https://thehill.com/policy/transportation/571597-dhs-to-increase-fines-for-mask-violations-in-airports-on-planes

New fed rule to require businesses with 100+ employees 'mandate vaccinations'

 President Joe Biden announced on Thursday that federal government employees and contractors will now be required to be fully vaccinated against COVID-19 and the Occupational Safety and Health Administration will create a rule for private businesses with 100 or more employees to require their employees to be vaccinated or undergo weekly testing.

Biden was laying out his new six-part strategy to combat the delta variant in remarks from the White House.

A senior administration official estimated that this new OSHA requirement will cover about 80 million workers and businesses that do not comply with the agency's rule can face substantial fees -- up to $14,000. OSHA will require these employers to offer paid time off for vaccination.

As part of his effort to vaccinate the federal executive branch, the Department of Defense, the Department of Veterans Affairs, the Indian Health Service and the National Institutes of Health will complete implementation of their previously announced vaccination requirements that cover 2.5 million people.

This is an escalation of the president's action in July calling for federal workers to attest to their vaccination status and submit to mitigation efforts if they are not vaccinated, such as mask usage and regular testing.

"We're in the tough stretch and it could last for a while," Biden said Thursday.

"To make matters worse, there are elected officials actively working to undermine the fight against COVID-19," he continued. "Instead of encouraging people to get vaccinated and mask up, they're ordering mobile morgues for the unvaccinated dying from Covid in their communities. This is totally unacceptable."

The president also announced that the Transportation Security Administration's interstate travel mask mandate will be extended through Jan. 18, the fine for noncompliance will double and health care facilities that receive Medicare and Medicaid reimbursement must require their employees to be vaccinated. This will cover about 17 million health care workers across the country.

"In total, the new vaccination requirements in the president's plan cover about 100 million workers, that's two thirds of all workers in the United States," a senior administration official said on a briefing call with reporters Thursday afternoon.

The largest federal law enforcement union FLEOA, pushed back on the president's vaccine mandate, in a statement released Thursday.

"A mandate at this time only undermines these voluntary vaccination efforts and reduces public comfort in getting vaccinated," President Larry Cosme said.

Speaking at her daily briefing Wednesday, White House press secretary Jen Psaki told reporters Biden would "outline the next phase in the fight against the virus and what that looks like, including measures to work with the public and private sector."

She said he would be "building on the steps that we've already announced, the steps we've taken over the last few months, requiring more vaccinations, boosting important testing measures and more, making it safer for kids to go to school, all at a time when the American people are listening. Again, this will be six steps that we'll work to be implementing over the months ahead."

According to a White House official, the president's plan will include six areas of focus: vaccinating the unvaccinated; furthering protection for the vaccinated; keeping schools safely open; increasing testing and requiring masking; protecting the economy's recovery; and improving care for those with COVID-19.

Psaki confirmed there will be new components as part of the president's announcement but wouldn't go much beyond general comments about testing access, mandates and making sure kids are protected from the highly transmissible virus as they return to school and Americans return from summer vacations.

She said plans were still being finalized as Biden met with with his COVID-19 response team Wednesday afternoon.

"Will any of those new steps influence the average American's day-to-day life? Should we expect any new mitigation recommendations, as an example?" a reporter asked.

"It depends on if you're vaccinated or not," Psaki replied, but gave no further details.

She highlighted efforts the administration already has taken to try and get the delta variant under control.

"We've been at war with the delta variant over the course of the last couple of months. And just to remind you of some of the steps that we have announced, we have announced new government mandates on DOD, our military forces, NIH, other -- the VA, the Veterans Affairs -- Department of Veterans Affairs, folks who are serving on the front lines on the health -- on health -- in health roles in that department. We've also incentivized additional mandates, whether it is in home -- in health care facilities, nursing homes, and others," Psaki said.

"And we've also lifted up and -- and incentivized private sector -- private sector mandates, because we've seen that they have been effective. We've also deployed over 700 surge response teams across the country and work closely, again, with the private sector to institute more requirements on vaccinations," she continued.

"We have more work to do, and we are still at war with the virus and with the delta variant," she added. "So, we're going to build on that work. And he's speaking to it now, because this issue, of course, is on front of mind, top of mind to Americans across the country. People are returning to schools. Workplaces are either reopening, some brick and mortar, or some people are just returning to work after spending some time with family or loved ones over the summer."

But besides ordering the nation's 2.1 million federal employees and 1.3 million active duty service members get vaccinated, Biden has limited legal authority to institute a broad vaccine mandate for most Americans.

About 75% of the adult U.S. population has received at least one vaccine dose and 64.4% of the adult U.S. population is fully vaccinated as of Wednesday, according to the Centers for Disease Control and Prevention.

On Tuesday, Psaki did seem to suggest that Biden will call on the private sector to institute more vaccine mandates. Major corporations such as Facebook, Google and Citigroup have already announced vaccination requirements.

"I will note that we've seen that there are a range of ways that we have increased vaccinations across the country, or vaccinations have increased, I should say. One of them is private sector companies mandating in different capacities that their employees get vaccinated. Or certain school districts mandate," Psaki said.

Biden previewed some of what he planned to say when he spoke about the August jobs numbers, which were much lower than predicted.

"There's no question the delta variant is why today's jobs report isn't stronger. I know people were looking, and I was hoping, for a higher number. But next week, I'll lay out the next steps that are going to -- we're going to need to combat the delta variant, to address some of those fears and concerns," Biden said Friday.

A recent ABC News/Washington Post poll showed Americans in August souring on Biden's handling of the pandemic, with his approval rating for his handling or the response dropping 10 points from June, down to 52%

Biden's remarks are scheduled for just 11 days before the administration is set to begin widely rolling out booster shots of Pfizer on Sept. 20, a process mired by confusion as some public health experts say the data doesn't yet support the need for boosters.

https://abcnews.go.com/Politics/biden-order-federal-workers-vaccinated-strategy-combat-delta/story?id=79905030

'New' Biden plan to lower drug prices drawn from familiar Dem playbook

 The Biden administration on Thursday unveiled a long-awaited plan to lower prescription drug prices that included a number of aggressive proposals but largely tread over ideas that Democrats have pushed for years.

The plan would allow Medicare to negotiate drug prices with manufacturers, a longstanding pledge from Biden, Democratic lawmakers, and every Democratic presidential candidate in 2020. It also would limit yearly price increases, allow the importation of drugs from Canada, and place a cap on out-of-pocket spending for Medicare beneficiaries.

“Life-saving prescription medication should not cost anyone their life savings,” Xavier Becerra, Biden’s health secretary, said in a statement. “Yet too often, many low-income families cannot take their prescription medications because of cost concerns.”

The plan, authored by the Department of Health and Human Services, follows through on a Biden executive order demanding a new report on strategies to lower prescription drug prices. None of it is binding, however, and it’s not clear whether the proposal will have any impact at all: Most of the plan relies on action from Capitol Hill, where Democrats are independently negotiating a number of drug pricing proposals.

The pharmaceutical industry has long warned that aggressive new plans to limit drug prices, particularly Medicare negotiation, could lead companies to reduce their research investment and, therefore, develop fewer new medicines. In particular, drug companies have cited the record-setting development of Covid-19 vaccines as evidence that the industry is better off without limits on revenue or profit.

The new plan provides new insight into the Biden administration’s stance on drug prices, a key issue for American voters. Notably, though, it includes few new proposals, instead relying on a number of standard-issue Democratic planks.

The plan would allow Medicare to negotiate the prices of drugs provided by two of its major programs: Part B, which covers drugs administered in hospitals, and Part D, which typically covers prescriptions filled in pharmacies.

The new prices would also be available to commercial plans, the White House said, effectively creating a nationwide price ceiling.

The plan also expresses support for bills aimed at bringing generic and biosimilar drugs to market more quickly, like shortening exclusivity periods, creating incentives for doctors to prescribe biosimilars instead of brand-name drugs, and imposing a ban on “pay-for-delay” schemes.

Notably, the plan makes no mention of a scheme to peg U.S. prices to what foreign governments pay for the same drugs. International reference pricing proposals, which the drug industry staunchly opposes, were central to recent drug pricing proposals from major political figures ranging from President Trump, Sen. Bernie Sanders (I-Vt.), and House Speaker Nancy Pelosi.

The report also steers clear of a controversial proposal from progressive Democrats to strip companies of exclusivity to brand-name drugs if the government determines they’re priced unreasonably. It acknowledges that such authority exists under a law known as Bayh-Dole, though, writing that “HHS will continue to give such petitions due consideration.”

The Biden administration plan also cites a new mechanism to speed the development of new cures: The new research agency known as ARPA-H, for which Biden has proposed $6.5 billion in new spending. The report argues that like other government scientific agencies, including the National Institutes of Health, “ARPA-H will help bring more new cures and treatments to patients.”

https://www.statnews.com/2021/09/09/new-biden-plan-to-lower-drug-prices-drawn-from-familiar-democratic-playbook/

DOJ sues Texas over 'unconstitutional' abortion law

 The Justice Department is suing Texas over the state's new controversial restrictions on abortions after six weeks of pregnancy, Attorney General Merrick Garland announced  Thursday.

Garland said the law is plainly improper both for its onerous restrictions on abortion access and for the provisions allowing state residents to sue anyone who aids or carries out restricted abortions.

 

"The act is clearly unconstitutional under longstanding Supreme Court precedent," Garland said at a press conference.

 

"This kind of scheme to nullify the Constitution of the United States is one that all Americans, whatever their politics or party, should fear," Garland said.

 

"If it prevails, it may become a model for action in other areas by other states and with respect to other constitutional rights and judicial precedents. nor need one think long or hard to realize the damage that would be done to our society if states were allowed to implement laws that empower any private individual to infringe on another's constitutionally protected rights in this way," he added. 

The move comes a week after the Supreme Court refused to block the state law, which would effectively ban most abortions, in a 5-4 ruling over the objections of the court's liberal wing and the Chief Justice John Roberts. The law went into effect on Sept. 1.

The lawsuit was filed Thursday afternoon in federal district court in Texas.

"The United States has the authority and responsibility to ensure that Texas cannot evade its obligations under the Constitution and deprive individuals of their constitutional rights by adopting a statutory scheme designed specifically to evade traditional mechanisms of federal judicial review," the lawsuit reads.

"The federal government therefore brings this suit directly against the State of Texas to obtain a declaration that S.B. 8 is invalid, to enjoin its enforcement, and to protect the rights that Texas has violated."   

A spokeswoman for Texas Gov. Greg Abbott (R) dismissed the legal challenge as a political ploy.

“The most precious freedom is life itself," said the governor's press secretary Renae Eze in an emailed statement.

 

"Texas passed a law that ensures that the life of every child with a heartbeat will be spared from the ravages of abortion. Unfortunately, President Biden and his Administration are more interested in changing the national narrative from their disastrous Afghanistan evacuation and reckless open border policies instead of protecting the innocent unborn. We are confident that the courts will uphold and protect that right to life,” the statement said.

 

Under the law, the abortion restrictions are enforced through civil litigation brought by private parties, who can be awarded up to $10,000 if their case is successful. That scheme creates liability not only for doctors and medical personnel who perform abortions but also for anyone who so much as drives a patient to obtain a restricted abortion.

That enforcement scheme also creates legal hurdles in court for those seeking to challenge the law, making it difficult to determine the correct parties to sue in order to block the law.

The administration's lawsuit asks for a court order nullifying the statute and prohibiting the state's officials and even private citizens from "implementing or enforcing" the law.

 

The Supreme Court's ruling last week incensed the Democratic Party and reproductive rights activists, with some warning that it had effectively overturned the court's landmark Roe v. Wade decision that found that women have a constitutionally protected right to obtain an abortion without excessive restrictions.

 

It also raised fears that Texas's success at the Supreme Court would open the door for a slew of Republican-controlled state legislatures to impose similar restrictions across the country.

 

"If another state uses the same kind of provisions to deprive its citizens of their constitutional rights ... we will bring the same kind of lawsuit," Garland said on Thursday.

https://thehill.com/homenews/administration/571556-justice-department-sues-texas-over-abortion-law

Biden to require COVID-19 vaccines, tests for millions of private workers

Biden will announce a new rule Thursday to require all private employers with 100 or more employees to mandate vaccines or weekly testing.

A senior administration official said the rule will be issued from the Department of Labor’s Occupational Safety and Health Administration (OSHA) "in the coming weeks," and the implementation timeline will likely mirror the roughly 90 day window other private sector employers, like Tyson Foods and United Airlines, have required.

The requirement could impact nearly 80 millions workers, the administration official said, and if a business fails to comply with the rule they could face fines up to $14,000 per violation. 

The new rule for employers is one in a series of new aggressive steps that Biden will announce in a speech Thursday evening to boost vaccination rates in the coming weeks and rapidly scale up the country's COVID-19 testing capacity, according to senior administration officials familiar with the plans. 

The new national strategy, dubbed "Path Out of the Pandemic," represents a redoubling of the administration's efforts to combat the threat of the delta variant of the coronavirus. The administration has muddled through a summer marked by rising infections and fierce resistance to public health measures from many Republican governors. 

Biden is also dramatically expanding vaccination requirements for health workers. Last month, the administration said it would require all staff at about 15,000 nursing homes to be vaccinated in order to receive Medicare and Medicaid funding, a move that would impact about 1.3 million employees. The rule is expected to be issued later this month.

Under the new plan, workers in most other health care settings that receive Medicare or Medicaid reimbursement, including major hospitals, will need to be vaccinated. The rules would impact 50,000 providers and about 17 million workers, but officials did not have an immediate effective date. 

The administration will also impose sweeping new vaccination requirements on federal employees and contractors. 

A senior administration official told reporters that under a new executive order to be announced by the president, federal employees will have 75 days to be fully vaccinated, with limited exemptions for religious or medical reasons. There will be no testing option. The order will cover about 100 million workers.

"It's simple; if you want to work for the federal government, you must be vaccinated. If you want to do business with the government, you must vaccinate your workforce," the official said.

Vaccines will also be mandatory for all teachers and staff at Head Start and Early Head Start programs, as well as schools and youth programs operated by the Department of Defense and the Bureau of Indian Education.

The embrace of mandates represents a major escalation for the administration, which was previously reluctant to impose them. 

President Biden will also call on governors to get all teachers and school staff vaccinated, and will urge schools to set up regular COVID testing, consistent with CDC guidelines. 

Public health experts think regular screening of children and staff will help stop infections from spreading.

The federal government in the spring set aside $10 billion in funding for COVID screening tests for teachers, staff and students, but few took advantage as cases dropped.

https://thehill.com/homenews/administration/571569-biden-to-unveil-covid-strategy-with-heavy-emphasis-on-vaccine

Premier, 11 health systems acquire minority stake in Exela to lock down drug supply

 In a bid to head off drug supply shortages, healthcare improvement company Premier Inc. and 11 of its partner health systems have acquired a minority stake in the holding company of Exela Pharma Sciences, the organizations announced Wednesday.

The deal will see Premier’s health system members gain an uninterrupted supply of 19 pharmaceutical products developed and manufactured by the specialty pharma company at its Lenoir, North Carolina, location, according to the announcement. Of note, that includes Exela’s 503B pharmaceutical products and several injectables the companies said are often in short supply.

“Leveraging Exela’s significant production capacity, this collaboration is expected to give Premier’s participating members uninterrupted access to high-quality, U.S.-made pharmaceutical products and safety stock,” Michael J. Alkire, president and CEO of Premier, said in a statement. “With this investment, we are committing to support the domestic production of vital medicines for our members and the market—and to bring much-needed solutions to help eliminate drug shortages.”

Financial terms of the deal were not disclosed, although Premier said the investment is not expected to materially impact the results of its 2022 fiscal year.

According to the announcement, the 11 participating health systems have each signed multiyear commitments to purchase Exela’s products through Premier’s group purchasing organization.

The announcement named 10 of these provider organizations: Baystate Health, Genesis Health System, Henry Ford Health System, McLaren Health Care, Memorial Healthcare System, OSF HealthCare, Riverside Health System, Saint Francis Health System, Texas Health Resources and Universal Health Services.

The deal will help health systems cut down on regional or emergency-related drug shortages while supporting domestic drug manufacturing infrastructure, the companies said in the announcement.

These types of supply chain shortcomings have become stark throughout the COVID-19 pandemic and have increased hospitals’ costs for medical supplies, personal protective equipment, construction materials and more.

The latest investments also recall some of the supply chain deals the partners have made over the past year or so.

In May 2020, Premier and 15 health systems banded together to purchase a minority stake in Prestige Ameritech, the largest domestic manufacturer of PPE such as face masks. Near the tail end of that year, a partnership between global medical manufacturer DeRoyal, Premier and 34 health systems yielded a joint venture dedicated to domestic production of PPE.

https://www.fiercehealthcare.com/hospitals/premier-11-health-systems-acquire-minority-stake-exela-to-lockdown-drug-supply