Madrigal’s NASH candidate looks more cost-effective than Intercept rival, ICER says

 Drugmakers large and small have faced setbacks in advancing potential drugs against non-alcoholic steatohepatitis (NASH). Now that two appear to be nearing the market, the cost watchdogs at the Institute for Clinical and Economic Review (ICER) are weighing in on potential pricing.

Madrigal Pharmaceuticals’ resmetirom fared better than Intercept’s Ocaliva (obeticholic acid) in a draft assessment by ICER looking at potential cost-effectiveness in treating non-alcoholic steatohepatitis.

There are no approved treatments for the disorder which affects between 1.5% and 6.5% of adults in the United States. But several therapies are in development, with FDA decisions possible for resmetirom and obeticholic acid in 2023.

In ICER’s study, an annual placeholder price of $19,000 for resmetirom would provide cost savings over a lifetime of care for NASH patients, ICER said. Meanwhile, Ocaliva’s current list price of $85,000 would need to be reduced dramatically to make it cost-effective.

These findings come in the form of a draft report, which marks the midpoint of an 8-month review process, ICER stressed.

ICER derived its resmetirom pricing placeholder from a 2022 study of potential NASH treatments, the group said. Obeticholic acid's placeholder price is based on its 2022 wholesale acquisition cost in its approved use of primary biliary cholangitis.

In reviewing the findings, Intercept said that it does not believe that ICER's economic model does not "include the full breath of publicly available information" on its drug.

"We believe that the draft Evidence Report fails to fully reflect the potential clinical and economic value of OCA for patients with pre-cirrhotic fibrosis due to NASH, particularly those with advanced fibrosis without cirrhosis," a company spokesperson wrote. "Further, it’s premature for ICER to assign a price to OCA in NASH in this model as a price cannot be determined until after the FDA review process concludes. We continue to work with the FDA as they review our new drug application in consideration of determining the product label."

Both resmetirom and obeticholic acid appear to improve survival and quality of life in NASH, but based on ICER’s analysis of trial data, resmetirom is the more promising treatment.

“Resmetirom appears to reduce progression, promote regression of fibrosis, and lead to resolutions of NASH compared with placebo,” Boston-based ICER wrote. 

By contrast, ICER saw a “moderate certainty of small or substantial net benefit” with obeticholic acid and with more potentially negative consequences, citing cardiovascular issues and the incidence of pruritis as a common side effect.

NASH is caused by a buildup of fat in the liver which can lead to inflammation, scarring and cirrhosis. The condition isn’t necessarily progressive. It is similar to the liver disease caused by heavy drinking but NASH occurs in people who don’t abuse alcohol. There is no cure. Diet modification and exercise can slow its progression.

In December, Philadelphia-based Madrigal reported results from a phase 3 study showed that both 80-mg and 100-mg daily doses of resmetirom hit both liver histological improvement endpoints that the FDA had proposed as reasonably likely to predict clinical benefit.

"ICER’s initial draft assessment is aligned with our belief that resmetirom has the potential to be a cost-effective specialty therapy for patients," said Madrigal, which added that it plans to file file a new drug application seeking accelerated approval of resmetirom in the first half of this year. 

Obeticholic acid is up for a June decision in NASH, New Jersey-based Intercept said last month, while warning that the date is subject to change.

The drug was rejected by the FDA for use against NASH in 2020 but data from the phase 3 REGENERATE trial showed that obeticholic acid helped patients with advanced but pre-cirrhotic NASH achieve at least one stage of liver scarring improvement with no worsening of NASH after 18 months.

Aside from these potential treatments, multiple other drugs have entered the "NASH graveyard" after failed studies, including Genfit's elafibranor and Gilead’s selonsertib.

https://www.fiercepharma.com/pharma/madrigals-nash-candidate-tops-intercept-rival-icer-cost-effectiveness-assessment

Blinken claims China ‘strongly considering’ providing Russia with ‘lethal assistance’

 Secretary of State Antony Blinken said China is “strongly considering” providing Russia with “lethal assistance” in its nearly year-long war with Ukraine.

Blinken, who met with his Chinese counterpart Wang Yi on the margins of the Munich Security Conference on Saturday, said he warned Beijing against such a move.

“China is trying to have it both ways,” Blinken told NBC News’ Chuck Todd in an interview set to air on Sunday. “Publicly, they present themselves as a country striving for peace in Ukraine. But privately, as I said, we’ve seen already over these past months the provision of non-lethal assistance that does go directly to aiding and abetting Russia’s war effort.”

He added that further information indicates that Beijing is considering providing “materiel support to Russia’s war effort that would have a lethal effect.”

However, Blinken noted that China has not yet provided lethal assistance to Russia.

“We see China considering this. We have not seen them cross that line,” he said. “So, I think it’s important that we make clear, as I did this evening in my meeting with Wang Yi, that this is something that is of deep concern to us.” 

“I made clear the importance of not crossing that line and the fact that it would have serious consequences on our own relationship, something that we do not need on top of the balloon incident that China is engaged in,” Blinken added.

U.S.-China relations have been particularly tense in recent weeks, after a suspected Chinese spy balloon was spotted hovering over the U.S. The balloon spent about a week traversing the U.S., before it was shot down off the coast of South Carolina on Feb. 4. 

Blinken’s trip to Beijing was postponed amid the balloon drama, with a State Department official calling the balloon’s presence in U.S. airspace a “clear violation of our sovereignty as well as international law.”

Wang, who serves as the director of the Office of the Central Foreign Affairs Committee, mocked Washington’s response to the Chinese balloon while at the Munich Security Conference on Saturday, calling it “hysterical.”

Blinken’s interview with NBC News’ “Meet the Press” will air on Sunday morning on NBC.

https://thehill.com/policy/international/3864815-blinken-claims-china-strongly-considering-providing-russia-with-lethal-assistance/

Trudeau Responds To Leak Saying Beijing Interfered In 2021 Election To Back Liberal Minority

 by Andrew Chen via The Epoch Times (emphasis ours),

Prime Minister Justin Trudeau has responded to a news report about leaked Canadian Security Intelligence Service (CSIS) documents detailing how China used a strategy to interfere in the 2021 federal election in order to return the Liberals to office.

The Feb. 17 Globe and Mail article cited top-secret CSIS documents covering the period before and after the September 2021 election campaign which resulted in a minority Liberal government. That result was one of the goals of the interference, while Beijing also sought the defeat of Conservative MPs it deemed critical of the regime, the Globe reported.

Beijing’s desire for a second Liberal minority in Parliament was to ensure that Trudeau’s power would be kept curtailed, according to the CSIS documents.

“I have been saying for years, including on the floor of the House of Commons, that China is trying to interfere in our democracy, in the processes in our country, including during our elections. We are aware of this,” Trudeau told reporters on Feb. 17, hours after the Globe article was published.

“This is not a new phenomenon. This is something that countries around the world have been grappling with for a long time and Canada is no exception.”

Trudeau also insisted that the Canadian election process is intact.

“For the 2019, and for the 2021 elections, and for elections going forward, this government created a panel of top civil servants, who would lean on all the information provided to them by our security agencies like CSIS to ensure that interference by foreign actors does not affect the running or the outcomes of our elections,” he said.

“All Canadians can have total confidence that the outcomes of the 2019 and the 2021 elections were determined by Canadians and Canadians alone.”

The Globe report noted that the Security and Intelligence Threats to Elections (SITE) Task Force, established by the Trudeau government to monitor threats to federal elections, never raised the issue of foreign interference during the 2019 or 2021 campaigns.

This was further supported by Walied Soliman, who served as the Conservative party representative to SITE.

“I can confirm that after extensive security clearances and multiple meetings with our security establishment in Ottawa, these specific threats to our democracy were *never* raised, despite what is now clear evidence of tampering by China in the 2019 election,” Soliman wrote on Feb. 17 on Twitter in response to the Globe report.

“What’s worse: our party was seeing clear signs of tampering in ridings with substantial Chinese diasporas. We made the conscious decision to work through the Task Force and appropriate security channels. Our concerns were never taken seriously.”

When asked if the leaked documents signal a discomfort within CSIS about the government’s inaction, Trudeau said the agency needs to review its security.

“It’s certainly a sign that security within CSIS needs to be reviewed, and I am expecting CSIS to take the issue very seriously,” he said.

Following the publication of the Globe’s report, Bloc Quebecois and Conservative MPs weighed in on criticizing the Liberal government.

“Today the Globe & Mail reported that CSIS documents confirm “Chinese diplomats and their proxies backed the re-election of Justin Trudeau’s Liberals,” Conservative MP Raquel Dancho wrote on Twitter.

“Parliament must investigate these reports thoroughly and transparently.”

The Epoch Times has not seen the original CSIS documents.

Beijing Interference Operation

According to the CSIS documents reported on by the Globe, Beijing instructed its diplomats and other proxies—including some Chinese-language media—to propagate the idea that Conservative MPs were too critical of China, and that, once elected, they would follow the lead of former U.S. President Donald Trump and ban Chinese students from certain universities or education programs.

“This will threaten the future of the voters’ children, as it will limit their education opportunities,” a Chinese Consulate official said, according to the CSIS documents as reported by the Globe.

“The Liberal Party of Canada is becoming the only party that the PRC can support,” the official added, according to the report.

Beijing’s interference tactics involved “pressuring its consulates to create strategies to leverage politically [active] Chinese community members and associations within Canadian society,” as well as using Canadian organizations to advocate on behalf of China, the article said.

The CSIS documents said former Chinese consul-general in Vancouver, Tong Xiaoling, had bragged in 2021 about how she helped defeat two Conservative MPs.

In early November 2021, CSIS reported, Tong discussed the defeat of a Vancouver-area Conservative, whom she described as a “vocal detractor” of the Chinese regime. The Globe said an unidentified national-security source said that the MP was Kenny Chiu, then Tory MP for Steveston–Richmond East, B.C.

When asked about Tong taking credit for the defeat of Conservative MPs, Trudeau said it’s not surprising.

“The fact that a Chinese diplomat would try to take credit for things that happened is not something that is unseen in diplomatic circles around the world,” he said.

“The fact is, the work that CSIS has done, including with our election integrity panel, headed by our top public servants, … will always ensure that any risks to our election or to the integrity of those elections get highlighted to Canadians.”

The CSIS documents also say that the Chinese Communist Party leadership in Beijing was “pressuring its consulates to create strategies to leverage politically [active] Chinese community members and associations within Canadian society.”

The regime uses Canadian organizations to act on its behalf “while obfuscating links to the People’s Republic of China,” the documents said, according to the Globe.

The documents also said people sympathetic to Beijing’s cause were encouraged to give campaign donations to candidates favoured by China, the Globe said. Political campaigns would then quietly return a portion of the contribution—“the difference between the original donation and the government’s refund”—to the donors, which is illegal, the report added.

The anonymous national-security source told the Globe that nine Liberal and two Conservative candidates were favoured by Beijing, and that the two Conservative candidates were viewed as friends of China.

https://www.zerohedge.com/geopolitical/trudeau-responds-leaked-csis-files-saying-beijing-interfered-2021-election-support

Medicare to collect drug price rebates starting in 2025

 Drugmakers will be required to pay rebates to the federal government for price increases in Medicare that exceed the rate of inflation beginning in 2025, the Centers for Medicare and Medicaid Services said Thursday.

The timeline is part of initial guidance the agency released for inflation-linked price hike limits, one of a set of reforms in last year’s Inflation Reduction Act that are aimed at reducing Medicare drug costs. The law also allows Medicare to negotiate prices for top-selling, single-source drugs and capped monthly insulin costs for the program’s participants.

“The Medicare Prescription Drug Inflation Rebate Program will require drug companies with excessive increases in drug prices to pay rebates to Medicare,” CMS Administrator Chiquita Brooks-LaSure said in a statement.

The law requires drugmakers pay a penalty for Medicare drug price increases that rise faster than inflation, a limit that began in October for certain physician-administered Plan D drugs in Medicare and in January for certain self-administered Plan B drugs.

CMS will accept comments on the guidance until March 11 and revisions will be released in the fourth quarter. The agency said in a timeline it will tell drugmakers what rebates they owe for prices that exceeded the inflation rate in 2023 or 2024 by Sept. 30, 2025 for Plan B drugs and by Dec. 31, 2025 for Plan D drugs.

Drug manufacturers will receive a preliminary rebate report that will allow them to flag errors in calculations, which will be based on Medicare average sales prices over a 12-month period for Plan D drugs and over each quarter for Plan B drugs.

Later this spring, CMS is due to release initial guidance for its more wide-reaching reform — how it will negotiate prices for a first set of 10 drugs that will be published by September 2023 under a timeline released last month. CMS can negotiate prices for a total of 60 drugs that lack competition by 2029.

The drug industry has warned the law will have negative effects on research, and has the ear of some in the Republican party. Three GOP senators last year introduced a bill to repeal the law’s drug pricing provisions, but President Biden this week warned he would fight any attempts to roll back the law’s price reforms.

Meanwhile, Democratic lawmakers welcomed the latest rollout, which also adds limits to some Medicare participants’ copays for drugs starting April 1.

“I’m pleased to see CMS beginning this transformational Medicare policy to protect seniors from price gouging by drug companies,” Senate Finance Committee Chair Ron Wyden, D-Ore., said in a statement Thursday. “There have never been price gouging penalties in Medicare before, and I am confident that these policies are going to deliver real savings for Americans.”

https://www.biopharmadive.com/news/cms-medicare-drug-price-rebates-inflation-guidance/642513/

CMS plans trio of experiments aimed at lowering drug costs

 The Biden administration on Tuesday proposed three pilot programs aimed at lowering costs and improving access to drugs under Medicare and Medicaid, including gene therapies and medicines cleared via accelerated approval.

In the first program, the Centers for Medicare and Medicaid will test capping co-pays at $2 per month for commonly used generic drugs for chronic conditions. The other two would centralize outcomes-based agreements to improve access to expensive cell and gene therapies, and rework how CMS pays for certain drugs approved by the Food and Drug Administration on an accelerated basis “to encourage timely confirmatory trial completion.”

The payment models follow efforts begun last year to reduce Medicare drug costs through the Inflation Reduction Act, which gave CMS the ability to negotiate prices for a select number of Medicare’s top-selling drugs that lack competition. President Joe Biden later signed an executive order that called for new healthcare payment and delivery models.

CMS said it would consult with the FDA on how to implement the pilot payment program for drugs with accelerated approvals in 2023 and launch it “as soon as feasible.”

The FDA’s accelerated approval program has been under increased scrutiny because of some drugmakers’ long delays in completing confirmatory trials. CMS said it will test making “targeted adjustments” to payments to incentivize manufacturers to finish the trials.

Many details are still unclear: “We’re not able to say at this point exactly what those adjustments might look like,” CMS Administrator Chiquita Brooks-LaSure said on a press call Tuesday.

But the model could open a way to pay less for drugs that have obtained speedy approvals until further evidence proves their benefit, or to vary payment based on which disease they treat. 

“Structured right, this CMS proposal could allow drug pricing to match the level of evidence; enabling patients to access breakthrough drugs earlier, at lower prices, and as stronger confirmatory clinical evidence emerges, permit prices [to] adjust to reflect the proof of wider benefit,” former FDA commissioner Scott Gottlieb wrote in a tweet.

The pilot program is separate from Medicare’s restrictive policy on Alzheimer’s drugs approved on an accelerated basis, which last year limited coverage to only people enrolled in a clinical trial. CMS has faced pressure from patient groups to reconsider the policy. On Tuesday, Brooks-LaSure reiterated the agency’s message last month that it may revisit the policy based on new information about the drugs, which include Eisai and Biogen’s recently OK’d treatment Leqembi. 

“We continue to be open to hearing new data from manufacturers and advocates,” Brooks-LaSure said, adding that this class of drugs “is unique … our set of decisions around that don’t necessarily reflect our views of accelerated approvals more generally.”

The pilot program for cell and gene therapies, meanwhile, would seek to improve access to these one-time treatments, which can cost more than $1 million but promise many years of benefit. 

CMS would attempt to set up multi-state agreements with manufacturers, allow it to pool states’ bargaining power and better link payments to outcomes. The models could be announced by 2024 or 2025 and launched as early as 2026, starting within Medicaid and likely targeted to a single disorder such as sickle cell disease.

The $2 copay model — similar to practices by retail pharmacy chains to offer a list of drugs at low-cost, fixed prices — would include about 150 generic medicines used to treat chronic conditions like hypertension for those enrolled in one of Medicare’s drug plans.

https://www.biopharmadive.com/news/biden-cms-drug-pricing-experiment-model-accelerated-approval/642814/

Cigna restricts coverage of new ALS drug, deepening fears about access

 One of the nation’s largest healthcare insurers has changed its policy for a new and in-demand ALS medicine, deciding not to cover it due to “a lack of clinical efficacy data.”

Cigna considers the medicine, called Relyvrio, to be “experimental, investigational or unproven” and now won’t cover it for the treatment of ALS, or amyotrophic lateral sclerosis. Relyvrio was developed by the Massachusetts-based biotechnology company Amylyx Pharmaceuticals, and approved by the Food and Drug Administration last September.

“We want people living with ALS to have affordable access to effective, safe treatments,” Cigna said in a statement to BioPharma Dive. “Right now, there is not enough clear clinical evidence to support Relyvrio’s effectiveness so it is not currently covered on our standard formularies.”

“However, patients who meet certain clinical criteria may still be able to get coverage for it, depending on their plan,” Cigna added.

Previously, the insurer had covered Relyvrio if patients met a list of eight criteria and had been prescribed the drug by a physician who specializes in ALS treatment.

Cigna’s new policy is likely to further fuel concerns among patients and healthcare providers, who have feared that insurance companies will restrict access to Relyvrio, as they have in the past for other expensive rare disease medications. Amylyx set Relyvrio’s price tag at $158,000 per year.

Delays to treatment are especially daunting in diseases that rapidly progress, as ALS does. Patients with the disorder, which is hallmarked by the progressive decaying of nerve cells, often die within two to five years after first showing symptoms.

At Duke University’s ALS clinic, several patients’ applications for Relyvrio coverage have been denied by various insurers. But compared to Cigna, “no other company is anywhere near this extreme,” according to director Rick Bedlack.

“If we don’t do something about this, I worry that others will see this and soon follow suit,” said Bedlack, who has consulted with Amylyx in the past.

Stephen Scelsa, a neurologist at Mount Sinai Health System in New York and director of its ALS center, hasn’t seen any denials from Cigna yet, though he notes that’s not a common insurance among the clinic’s patients. (Scelsa has previously advised and received grant funding from Amylyx.)

Rather, most of the denials have involved ALS patients whose disease is more advanced than those who participated in the clinical trial that led to Relyvrio’s approval. That study enrolled nearly 140 participants, and found those given Amylyx’s drug as opposed to a placebo declined a bit slower in their ability to perform essential functions like speaking, writing and walking. It also showed Relyvrio-treated patients lived a median of about five months longer.

Amylyx is now running an additional, much larger trial to confirm the benefits of its drug. The trial finished enrolling patients last week, and is expected to produce data next year.

“We will continue to closely monitor developments as Relyvrio undergoes its confirmatory clinical trial, and will reevaluate its formulary status as more data is available,” Cigna said.

In its own statement to BioPharma Dive, Amylyx said it’s aware of Cigna’s commercial policy and has been in communication with the insurer about Relyvrio’s safety and effectiveness.

“Our payer interactions to date have been highly encouraging, and Cigna’s policy is an outlier, as we have seen strong positive coverage nationally,” Amylyx added.

For many ALS patients and their caregivers, Relyvrio has become a vital source of hope. Most drugs ever developed to treat the disease have failed in clinical testing. The FDA has only approved two other medications specifically for ALS, and the effects of both are considered modest.

Amylyx, therefore, is under pressure to ensure its drug gets covered by insurers and delivered to patients in a timely fashion. Investors are also watching closely, as Amylyx’s near-term financial future rests on a successful launch of Relyvrio.

https://www.biopharmadive.com/news/cigna-relyvrio-als-coverage-restrict-amylyx/642241/

Doing adoption the ‘right’ way can work for everyone involved

 The past year has not been good for the image of adoption. In the wake of the Dobbs decision rolling back abortion rights last June, the media has been filled with reports describing how adoption is “a traumatic event for everyone involved.” 

Adult adoptees, for instance, have detailed the crises they’ve often faced in life, with some even comparing adoption to colonization or slavery. Then there are the concerns about potential coercion pregnant women might face if abortion were to be restricted even further. 

But is any of this actually relevant?

Last year the American Enterprise Institute contracted with the National Opinion Research Center (NORC) to learn more about the demographics and experiences of birth mothers who placed their children up for adoption.

Using data from Spence-Chapin Services to Families and Children — the oldest adoption agency in New York — we were able to examine the outcomes for hundreds of women who opted for adoption between 2006 and 2020.

NORC researchers examined more than 700 anonymous administrative records, surveyed 60 birth mothers online and conducted a number of in-depth interviews to get a sense of who these women were and how their lives unfolded after their babies were placed with adoptive parents.

Spence Chapin facilitates private adoptions in which a mother voluntarily decides to give up her child. (This is different from adoption out of the foster-care system, in which a child who has been abused or neglected has been permanently removed from their family by a state agency and placed with another family.) Spence Chapin presents all options (including abortion and financial/social support if they decide to keep their children).

For those who decide to give birth, the agency offers women “interim care,” that is, vetted volunteers will care for newborns for up to a month while the mother decides whether she wants to complete the adoption. Although interim care is a rare practice for agencies, it has the virtue of allowing mothers more time to make what is clearly a very difficult decision.

This process also creates a kind of natural experiment where we can understand some of the factors associated with making this decision and compare those who end up parenting with those who opt for adoption.

The study’s results were intriguing.

The average age of the mothers who decided on adoption was 27, compared to 24 for mothers who chose to parent. The group who chose adoption were more likely to have a bachelor’s degree, speak English and be white than the people who kept their babies. There were no major differences in the marital status of the two groups and their families were about equally likely to know about their decisions. These factors suggest that notions about women who choose adoption being coerced by family or community stigma may be outdated. 

While it was an impossible choice for these women, Spence Chapin’s multi-pronged process seemed to help. Some 96% of the survey respondents said they found the interim baby care to be “helpful” or “extremely helpful.”

As one participant told an interviewer, “Even though I was pursuing adoption, I was pretty clear . . . that I wasn’t going to . . . make my decision for sure until the baby had left my body because . . . I don’t know how I’m going to feel.” 

The respondents also made clear that knowing their legal and emotional interests were being represented during this process was also very important. As one recalled, her social worker didn’t even use the term “birth parent” while she was pregnant because she wanted to leave open the possibility of her keeping the child. She said she appreciated that her social worker represented only her. “She didn’t have any adoptive families in her ear, being like, hey, like . . . can we get a kid?”

While there is older research suggesting that women who place children for adoption are “at risk for long-term physical, psychological, and social repercussions,” the vast majority of participants in our study reported being extremely satisfied with their life outcomes.

Of those who responded to the survey, 78% reported being either satisfied or extremely satisfied with their “emotional well-being,” 82% with their “physical safety,” 71% with their “romantic relationships,” 80% with their family, and 81% with their careers.

Though the survey participants were self-selecting and it is hard to generalize about all adoptive mothers, the reports suggest that for many women, life after placing a child for adoption is not simply a story of trauma. 

Spence Chapin mothers also appreciated the choices they had for families in which to place their babies. These include same-sex couples, couples of all faiths and races. And most were satisfied with the ongoing contact they had with their children — all the adoptions were open. 

If there are communities that, in the wake of Dobbs, find themselves with more unwanted babies, it’s crucial that our adoption practices be as fair, compassionate and transparent as possible. Understanding the needs of birth mothers is the first step. Americans mostly have positive views of adoption. But too often we we allow pundits and politicians to disparage the institution without bothering to research the experiences of those involved. Sharing these experiences is the best way to serve mothers and children. This report is a necessary first step toward making that happen.

https://nypost.com/2023/02/18/doing-adoption-the-right-way-can-work-for-everyone-involved/