GSK Builds Nucala’s COPD Case With Phase III Win

 

If approved in chronic obstructive pulmonary disease, Nucala will compete with Verona’s Ohtuvayre and—pending a potential approval later this month—Sanofi and Regeneron’s blockbuster Dupixent.

GSK on Friday announced topline results from the Phase III MATINEE trial, which found that its injectable antibody Nucala (mepolizumab) lessened exacerbations in patients with chronic obstructive pulmonary disease.

The pharma did not provide specific data in its announcement, only revealing that after following patients for up to two years, Nucala led to a “statistically significant and clinically meaningful reduction” in annual rates of moderate or severe exacerbations, compared with placebo. In terms of safety, Nucala’s adverse events in MATINEE were consistent with its known profile.

Further analysis of MATINEE continues and GSK will present full findings from the trial at a future scientific congress. The pharma will also share trial results with health regulatory authorities. Nucala is currently not approved for chronic obstructive pulmonary disorder (COPD).

Administered via a subcutaneous injection, Nucala is a monoclonal antibody designed to target the IL-5 cytokine, which is principally responsible for the growth, activity and survival of eosinophils. By binding to inhibiting IL-5, Nucala helps dampen the inflammatory response which is an underlying mechanism in various respiratory conditions.

The FDA first approved Nucala in November 2015 for the treatment of severe asthma in patients aged 12 years and older. Since then, Nucala has expanded into other indications including chronic rhinosinusitis with nasal polyps (CRSwNP), eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES). According to its label, Nucala’s precise mechanism of action for asthma, CRSwNP, EGPA and HES has not yet been fully elucidated.

Through MATINEE, GSK is looking to push Nucala into COPD. The late-stage, double-blinded, randomized and placebo-controlled trial enrolled more than 800 patients who received either Nucala or placebo on top of their usual, optimized maintenance therapies. Treatment lasted for at least 52 weeks, with a maximum duration of 104 weeks.

GSK’s COPD program for Nucala also includes METREX and METREO, which were completed in 2017.

Friday’s readout comes as the COPD space gears up for a potentially big approval later this month for Sanofi and Regeneron’s blockbuster antibody Dupixent. The partners are supporting their expansion bid with data from the Phase III BOREAS and NOTUS trials, which found that Dupixent could lower moderate or severe acute exacerbations while also boosting lung function.

The FDA accepted the supplemental Biologics License Application on February 2024 and gave it Priority Review, which means that the target action date should have been in June. However, weeks before its deadline, the regulator asked for additional efficacy data from BOREAS and NOTUS, which led to a delay in the review. The new PDUFA date is Sept. 27.

In the COPD space, Verona’s Ohtuvayre was approved in late June 2024 and represents the first novel mechanism of action for the condition in more than 10 years.

In the late-stage ENHANCE-1 and ENHANCE-2 studies, Ohtuvayre resulted in a respective 87-mL and 94-mL improvement in forced expiratory volume—a key measure of lung function. Verona’s drug also lowered exacerbations and prolonged the time before patients experienced their first exacerbation.

https://www.biospace.com/drug-development/gsk-builds-nucalas-copd-case-with-phase-iii-win

Travere Wins Full FDA Approval for IgAN Treatment Filspari

 

With the regulator’s traditional green light in IgA nephropathy, Filspari is up against Novartis’ Fabhalta—which won accelerated approval last month—and Calliditas’ Tarpeyo, which was approved in December 2023.

The FDA on Thursday granted traditional approval to Travere Therapeutics’ Filspari (sparsentan) for the treatment of patients with primary IgA nephropathy.

Filspari’s full approval expands its indication, allowing use of the small molecule blocker to slow the decline of kidney function in adult patients who are at risk of disease progression—while also removing a previous requirement of having a specific urinary protein level. According to Travere, Filspari is the only oral, once-daily and non-immunosuppressive treatment for IgA nephropathy (IgAN), specifically targeting glomerular injury in the kidney.

“Full approval now enables physicians to confidently prescribe Filspari more broadly as a once-daily, oral, non-immunosuppressive treatment, that can provide superior preservation of kidney function and replace current standard of care,” Travere CEO Eric Dube said in a statement. “Filspari is well positioned to become foundational care for IgAN as the treatment landscape evolves.”

Jefferies analyst Maury Raycroft in a note to investors said Filspari’s full approval was timed well with the new Aug. 30 draft guidance from the global nonprofit Kidney Disease Improving Global Outcomes (KDIGO). The recommendations lowered the urine protein-creatinine ratio (UPCR) threshold for at-risk patients while also raising treatment goals.

Filspari is one of the few agents that can satisfy the new KDIGO guidelines, according to Raycroft, who contends that Travere’s drug can address the immune and inflammatory drivers of IgAN while also targeting generic drivers of chronic kidney disease.

Designed to be taken orally, Filspari is a small molecule blocker of the endothelin and angiotensin II receptors, both of which are thought to play a role in the pathogenesis of IgAN, according to its label. Filspari comes with a boxed warning for hepatotoxicity and embryo-fetal toxicity and is available only through a risk evaluation and mitigation strategies program.

The FDA granted Filspari accelerated approval in February 2023 using proteinuria data from the Phase III PROTECT study. At the time, Travere had successfully shown that Filspari could lower urine protein levels more than three times as much as Avapro (irbesartan), the active control.

Travere kept PROTECT to serve as Filspari’s confirmatory trial, but in September 2023 the biotech announced that the trial had “narrowly” missed its efficacy endpoint of the total slope of estimated glomerular filtration rate (eGFR). Nevertheless, Dube continued to express confidence in Filspari and highlighted its effects on proteinuria and eGFR decline.

In Thursday’s announcement, Travere again touted Filspari’s clinical benefit, noting that the drug could significantly slow decline in kidney function. At week 110, patients on Filspari showed mean eGFR slope of –3.0 mL/min/1.73m²/year, as opposed to –4.2 mL/min/1.73m²/year in patients treated with Avapro. The treatment effect was statistically significant in favor of Filpsari, with a p-value of 0.0168.

In addition, long-term follow-up data from PROTECT showed that the 36-week benefit of Filpsari on proteinuria was durable through 110 weeks.

Travere competes with Calliditas Therapeutics and pharma giant Novartis in the IgAN space. In December 2023, Calliditas secured full approval for Tarpeyo (budesonide), while Novartis won accelerated approval for Fabhalta (iptacopan) last month.

https://www.biospace.com/fda/travere-wins-full-fda-approval-for-igan-treatment-filspari

ICE Headlines Are Wake-Up Call: Nation Sleepwalking Into Migrant Crisis Storm

 The radical progressive Biden-Harris-Mayorkas trio are destroying American sovereignty and endangering the lives of law-abiding citizens as armed Venezuelan prison gangs with AR-style rifles and pistols run amok in the northern Denver suburb of Aurora and other sanctuary cities run by far-left Democrats. We learned this week that migrant gangs were beginning to target critical energy infrastructure in West Texas. 

Since January 2021, the Biden-Harris-Mayorkas trio destroyed whatever border security the Trump administration built and facilitated the greatest migrant invasion this nation has ever seen, flooding cities and counties with millions of unvetted migrants, some of which have been confirmed as criminals and terrorists.

The breadth and depth of the continuing damage are only beginning to be realized as once-peaceful neighborhoods across the US, from New York City to Chicago to Denver to some West Coast cities, are plagued with migrant crime. Some municipalities are being overrun by illegal aliens as local resources are drained. 

Just chaos. 

A particularly alarming issue is in the Permian Basin, America's top oil-producing region, is now under threat from migrant gangs. This indicates that the nation's critical energy infrastructure is at risk.

What we've also told readers this week - is that law-abiding Americans must be made aware of the cities, counties, and states that have laws, ordinances, and policies that obstruct immigration enforcement and shield illegal alien criminals from US Immigration and Customs Enforcement. This is because these areas are increasingly becoming too dangerous - or perhaps 'no go' zones, with armed migrant criminals running amok. Aurora is a prime example.

The latest headlines from ICE's website are a major wakeup call this nation is sleepwalking into disaster:

• ERO Boston arrests Haitian national charged with sexually assaulting Massachusetts minor

• ICE Houston removes Salvadoran fugitive wanted for aggravated femicide, aggravated homicide and gang membership

• ERO Boston arrests Brazilian national charged with sex crimes against Massachusetts child

• Enforcement and Removal Operations Philadelphia arrests Brazilian national wanted for homicide in Brazil

• ICE Houston arrests 4-time previously removed convicted murderer from Mexico

• ERO Boston arrests Ecuadorian national charged with sex crimes against Massachusetts child

• ERO Houston removes 3-time deported Guatemalan fugitive with lengthy criminal history

• ERO New York City arrests fugitive wanted for homicide in Dominican Republic

• ERO Boston arrests noncitizen wanted by Mexican authorities for aggravated homicide

• ERO Washington, DC arrests Bolivian national convicted of sex crimes against Virginia minor

• ERO Baltimore arrests Guatemalan national convicted of assault in Maryland

• ERO Boston arrests Chinese national charged with sex crimes against Massachusetts residents

• ERO New York City arrests previously removed MS-13 gang member convicted of manslaughter

• ERO Boston arrests Brazilian national charged locally with attempted murder, stalking, kidnapping

Yeah. She said this... 

All of this chaos unfolding is the direct consequence of Biden-Harris-Mayorkas importing the third world into the first world.

https://www.zerohedge.com/political/ice-headlines-are-wake-call-nation-sleepwalking-migrant-crisis-disaster

Joy Behar Flusters Gov. Shapiro Turning Remark on Ana Navarro Into Something Dirty

 Another day, another awkward moment from Joy Behar on The View. On this morning’s episode of the hit daytime talk show, the longtime host had to get her mind of out the gutter after Pennsylvania Gov. Josh Shapiro apologized for not hooking up with Ana Navarro when she was visiting his home state this week.

Things between Behar and Shapiro, who was making his debut on The View, were shaky from the start, with the comedian telling him that “most” of her cousins who live in Pennsylvania approve of his work as governor.

“You’re super popular in Pennsylvania. My cousins live in Pennsylvania,” she said, before adding, “They like you. Most of them.”

Shapiro then asked, “Most?” to which Behar clarified, “Well, some of them are Trump supporters … but those are not blood, they’re in-laws.”

Navarro then jumped in to let Shapiro know that she was recently doing some work in Pennsylvania.

“I was just in Pennsylvania because we were doing something in Bethlehem with Puerto Ricans. I promised them you’re coming to see them. They love you too,” she said.

Upon the realization, Shapiro apologized for not meeting up with her during her trip.

“I’m sorry we didn’t hook up, that would be fun. We had to come to New York to do that,” he said, while a dirty-minded Behar chimed in, “Excuse me? Hook up?”

Photo: ABC

The politician attempted to explain what he meant, but Navarro quickly fired back, “Don’t start rumors!” At the same time, Alyssa Farah Griffin told Behar to “take us back on the rails.”

A flustered Shapiro then asked, “Was that on-air?” to which Behar nonchalantly confirmed, “Yeah, that was on-air.”

Fortunately, the awkwardness ended there. After talking politics through a couple of different segments, Shapiro concluded his visit by declaring his support for Kamala Harris, revealing that he’s in his “Speak Now” era when it comes to Taylor Swift music and saying he’s rooting for both the Eagles and the Steelers in the NFL (duh, he’s from Pennsylvania).

https://decider.com/2024/09/06/joy-behar-flusters-gov-josh-shapiro-remark-hooking-up-ana-navarro-dirty/

US Goes Ballistic Over New Iranian Missile Transfers To Russian Forces

 As another reminder of how these already dangerous and volatile wars in the Middle East and Eastern Europe are inter-connected, United States officials are slamming the Iranian government in the wake of fresh reports saying Tehran has transferred short-range ballistic missiles to Russia.

The Wall Street Journal was the first to report Friday that "Iran has sent short-range ballistic missiles to Russia, according to U.S. and European officials, a move that gives Moscow another potent military tool in its war against Ukraine and follows stern Western warnings not to provide those arms to Moscow."

The Pentagon and US intelligence has for months been warning about such a possibility, and has been threatening Iran over the potential move, but a US official has now "confirmed" to the WSJ that the missiles "have finally been delivered." The Biden White House has said "a severe response" to Tehran awaits.

NATO countries led by the US have been warning of swift and severe consequences, but the reality is at this point there's not too much left to sanction in either the Islamic Republic or Russia. Both are a couple of the most highly sanctioned countries on earth, which has only resulted in their deepening their relations, and turning to BRICS and non-aligned Global South countries. Group of 7 countries have said they will coordinate to punish Iran if missile deliveries to Russia's armed forces go through.

It's long been well-known that Russia has received thousands of Iranian kamikaze drones, which have for the last two-and-a-half years been a feature of the aerial assault on Ukrainian cities. The Islamic Republic is even helping Russia manufacture drones inside Russia.

The WSJ notes of the sensitive political timing of the alleged ballistic missile transfer and also the potential impact to the 'moderate' Pezeshkian administration on the global stage:

The missile deliveries also could have implications for the hopes of the new Iranian government to tamp down tensions with the West. The country’s new president, Masoud Pezeshkian, has said he hopes to improve the domestic economy by winning sanctions relief from Europe and the U.S.

But at this rate, this hoped-for sanctions relief is surely not going to happen. Late Friday, Iran issued a formal rejection of the contents of the WSJ report and the allegations of Western officials:

In a statement shared with Newsweek, however, the Iranian Mission to the United Nations stated that Iran had not provided weapons to either side of the conflict in Ukraine and called on other nations to cease doing so.

"Iran's position vis-à-vis the Ukraine conflict remains unchanged," the Iranian Mission said. "Iran considers the provision of military assistance to the parties engaged in the conflict—which leads to increased human casualties, destruction of infrastructure, and a distancing from ceasefire negotiations—to be inhumane."

"Thus, not only does Iran abstain from engaging in such actions itself but it also calls upon other countries to cease the supply of weapons to the sides involved in the conflict," the statement added.

We recently highlighted that Russia has appeared to step up supplies of air defense equipment to the Islamic Republic, at a moment Tehran is still threatening possible massive retaliation attacks on Israel for the July 31 killing of Hamas leader Ismail Haniyeh in Tehran. The expectation in such a scenario is that Israel's counter-response would be bigger. And yet for now it seems this escalation scenario has waned, given that over a month has passed and there's been no big strikes.

The Iranians are reportedly also pressuring Moscow to fulfill delivery of Su-35S fighter jet fighters which were previously pledged in a defense deal, given the regional temperature is heating up fast.

Moscow likely feels obliged given the significant Iranian drone transfers it has received throughout the course of the Ukraine war. Iran has heavily aided Russian forces, and now Russia is quickly coming to Iran's assistance.

https://www.zerohedge.com/geopolitical/us-goes-ballistic-over-new-iranian-missile-transfers-russian-forces

Poland's Official Story About An Alleged Airspace Violation Doesn't Add Up

 by Andrew Korybko via Substack,

The authorities’ story doesn’t add up since they still maintain that at least three radiolocation stations recorded a violation, but they also claim at the same time that no such violation ever occurred.

Major General Maciej Klisz announced that Poland’s ten-day search for physical evidence of last month’s recorded airspace violation came up empty-handed. According to him,

“As a result of this process and the undertaken analysis, I can say that with high likelihood the air space of the Republic of Poland was not breached on August 26…(but the) data has not changed, what changed is our assessment of the situation.”

For comparison’s sake, here’s what he said on that same day late last month:

“We are probably dealing with the entry of an object on Polish territory. The object was confirmed by at least three radiolocation stations. It is clear from its characteristics that the object is not a missile, it is not a hypersonic, ballistic or guided missile.”

Foreign Minister Radek Sikorski then started talking tough about Poland possibly shooting down Russian missiles over Ukraine, the subject of which was analyzed here.

Returning to Klisz’s remarks, it’s notable that he insisted that the “data has not changed”, thus meaning that Poland still maintains that at least three radiolocation stations recorded an airspace violation on 26 August, but they couldn’t discover any physical evidence inside of country. Nevertheless, he also flip-flopped by now concluding that Polish airspace wasn’t breached in the first place, which is contradictory. Notice that he’s not even speculating that a drone might have crossed in and out of Polish airspace.

If what he’s saying is true, then this means that Poland’s radiolocation stations are either malfunctioning or that Russia is somehow able to manipulate their signals, both scenarios of which are very concerning from the perspective of Polish national security. Another possibility is that debris from a Ukrainian air defense missile fell inside of Poland, but the authorities want to cover it up in order to not worsen bilateral relations and/or create a situation where more citizens sour on Polish aid to Ukraine.

The media should hold Klisz’s feet to the fire by pressing him and other officials to elaborate on his contradiction. They’re unlikely to get an answer, or whatever they receive might not directly address this, but it’s important that it’s not swept under the rug given the national security stakes involved. Poles and their NATO allies deserve to know whether Poland’s radiolocation stations are malfunctioning or being manipulated, or if a wayward Ukrainian air defense missile or its debris once again fell inside of Poland.

As it stands, this incident is already hugely embarrassing. Coming up empty-handed despite a ten-day search that covered 3,200 square kilometers from the air, 250 square kilometers on the ground, and analyzed satellite images of an area of 310 square kilometers where the object was likely to fall according to reports suggests that the full truth isn’t being shared. It also needlessly provoked panic among people who were duped into thinking that a Russian object supposedly violated Polish airspace.

Sikorski’s tough talk about possibly shooting down Russian missiles over Ukraine is also revealed to have been political opportunism that was advanced on what’s now officially considered to be a false pretext. The authorities’ story doesn’t add up though since they still maintain that at least three radiolocation stations recorded a violation, but they also claim at the same time that no such violation occurred. It’s therefore incumbent on truly independent members of the press to get down to the bottom of this.

https://www.zerohedge.com/geopolitical/polands-official-story-about-alleged-airspace-violation-doesnt-add

Absentee voting instruction violates law, North Carolina plaintiffs say

  Litigation filed against North Carolina’s State Board of Elections on Tuesday contests a memo of instruction to county boards of elections in conflict with absentee by mail ballot state laws.

For the board, it’s lawsuit No. 6 in 43 days, and the fourth in 12.

Virginia Wasserberg, registered in Pasquotank County, is joined by the North Carolina Republican Party and the Republican National Committee on the complaint. They say the state board sent instruction to the 100 county boards “that disregards election laws requiring absentee ballot security envelopes to be sealed in order for the ballot to count,” a release says.

“State law is clear in this matter and it is unfortunate that Director Bell is acting beyond her authority,” state party Chairman Jason Simmons said of Elections Board Executive Director Karen Brinson Bell. “We will continue to enforce integrity in the elections process and adherence to statutory requirements.”

The litigation says Numbered Memo 2021-03, an instruction from Bell, “issued guidance” and “undermines the protections afforded by the General Assembly’s carefully drafted absentee-voting statutes.” Four statute references are named that require “an absentee ballot must be received by the proper county board of elections in a sealed envelope for the ballot to be counted.”

Plaintiffs say the memo “advises county boards of elections that an absentee ballot may be counted even if it is not submitted in a sealed container-return envelope.”

A declaratory ruling to the board was rejected prior to the lawsuit being filed, the litigation says.

Defendants are the board as a whole, each member in their board capacity, and Bell. The board includes Democrats Alan Hirsch, its chairman, Jeff Carmon and Siobhan Millen; and Republicans Stacy Eggers and Kevin Lewis.

Since July 22, the state board has been litigated because of decisions related to ballot access involving the Justice For All Party, and the We The People Party; voter roll maintenance twice; and freedom of speech involving John F. Kennedy Jr.

https://nypost.com/2024/09/07/us-news/north-carolina-absentee-voting-violates-state-law-plaintiffs-say/