AstraZeneca, Amgen’s Phase III Win Strengthens Case for Tezspire Expansion

 

The partners are building toward a regulatory submission for Tezspire in chronic rhinosinusitis with nasal polyps in the first half of 2025.

While regulatory preparations are underway, powerhouse partners AstraZeneca and Amgen continue to beef up their case for the expansion of the subcutaneous antibody Tezspire into chronic rhinosinusitis with nasal polyps.

Full data from the Phase III WAYPOINT trial showed Tezspire could elicit a more than 2-point reduction in the Nasal Polyp Score (NPS) at 52 weeks versus placebo. Similarly, the biologic lowered patient-reported Nasal Congestion Score (NCS) by more than 1 point as compared with placebo. Both treatment effects were highly statistically significant, according to the companies’ announcement.

Aside from hitting its co-primary endpoints NPS and NCS, Tezspire also aced key secondary outcomes, including the time to first use of a systemic glucocorticoid, loss of smell, total symptom score and the time before patients decide to undergo surgical removal of their polyps. Tezspire also reduced the need for subsequent surgery by 98% and for systemic corticosteroids by 88%, according to the companies.

AstraZeneca and Amgen presented the data Saturday at a late-breaking oral presentation at the Joint Congress of the American Academy of Allergy Asthma & Immunology (AAAAI) and World Allergy Organization, held in San Diego.

In an investor note on Sunday, analysts at Leerink Partners also took the WAYPOINT readout as a positive for Amgen and AstraZeneca, noting that Tezspire “demonstrated marginally better efficacy cross-trial vs. Dupixent,” with better NPS and NCS improvements.

Still, the analysts cautioned that cross-study comparisons could be fraught, particularly given “trial inclusion differences.” WAYPOINT, in particular, “enrolled a more selective group regarding respiratory comorbidities, but a broader population in terms of prior surgery,” the analysts noted.

Sharon Barr, executive vice president of biopharmaceuticals R&D at AstraZeneca, said Saturday’s readout points to the “potential of Tezspire to provide a much-needed option for patients with chronic rhinosinusitis with nasal polyps (CRSwNP).”

“With its first-in-class mode of action, targeting TSLP [thymic stromal lymphopoietin] at the top of the inflammatory cascade, the data add to the body of evidence that tezepelumab can transform care for patients with epithelial-driven inflammatory diseases,” Barr added.

TSLP is a cytokine that is a crucial upstream player in the inflammatory cascade. Tezspire, a humanized IgG2 monoclonal antibody, works by binding to TSLP and preventing its interaction with its corresponding receptor, thereby disrupting the inflammation pathway.

This mechanism of action won it the FDA’s approval for severe asthma in December 2021, backed by data from the Phase III NAVIGATOR trial, where Tezspire significantly reduced the annualized rate of asthma exacerbations versus placebo, while also eliciting improvements in lung function, symptom burden, disease control and quality of life. Tezspire can only be used in patients aged 12 and above.

In its fourth-quarter business presentation, Amgen disclosed that it was preparing to file regulatory submissions for Tezspire in CRSwNP in the first half of 2025. Beyond asthma and CRSwNP, AstraZeneca and Amgen are studying Tezspire for other inflammatory respiratory indications, including chronic obstructive pulmonary disease and eosinophilic esophagitis.

https://www.biospace.com/drug-development/astrazeneca-amgens-phase-iii-win-strengthens-case-for-tezspire-expansion

Lexicon Phase 2b pain trial misses statistical significance on primary endpoint

 In the PROGRESS study, all pilavapadin treatment arms demonstrated reductions in the mean average daily pain score (ADPS) from baseline to Week 8 with the 10 mg, 20 mg/10 mg and 20 mg dose arms achieving reductions of 1.74, 1.70 and 1.38, respectively, compared to a reduction of 1.31 in the placebo arm. The study’s statistical analysis plan was designed to detect a dose-response signal based on a prespecified model that assumed separation of all treatment arms from placebo when measuring the primary endpoint of change from baseline to Week 8 on ADPS as compared to placebo. As a result of the lack of separation in ADPS reduction between the 20 mg dose arm and placebo, the study results did not reach statistical significance on the primary endpoint (p=0.11). However, the 10 mg dose arm demonstrated clear evidence of effect by achieving early and clinically meaningful separation from placebo on ADPS that was maintained throughout the study duration.

Adverse events were more frequent in the pilavapadin treatment arms, but were significantly improved from the RELIEF-DPN-1 study across all doses. Nearly all adverse events were reported as mild or moderate. Adverse events were most prominent at the 20 mg dose and pilavapadin was generally well-tolerated at the 10 mg dose. Dizziness and nausea were the most commonly reported adverse events and the most frequently associated with patient discontinuations from the study, which occurred most predominantly in the 20 mg dose.

On the basis of the PROGRESS study results in the 10 mg dose arm, together with the previous findings from RELIEF-DPN-1, Lexicon has identified 10 mg once daily as an appropriate dose to advance into Phase 3 clinical development for DPNP.

Lexicon management will hold a live conference call and webcast today at 8:00 a.m. ET / 7:00 a.m. CT to review the details of this announcement. Participants can access the conference call live via webcast on the Events page of the Company’s website at https://investors.lexpharma.com/. Participants who wish to ask a question may register here to receive dial-in numbers and a unique pin to join the call. An archived version of the webcast will be available on the Lexicon website.

https://www.globenewswire.com/news-release/2025/03/03/3035469/0/en/Lexicon-Pharmaceuticals-Announces-Topline-Results-from-Phase-2b-PROGRESS-Study-Evaluating-Pilavapadin-LX9211-in-Adults-with-Diabetic-Peripheral-Neuropathic-Pain.html

Pliant discontinues pulmonary fibrosis trial

 Pliant Therapeutics, Inc. (Nasdaq: PLRX) today announced that following a prespecified data review and recommendation by the trial’s independent Data Safety Monitoring Board (DSMB), as well as a secondary review and recommendation by an outside expert panel, Pliant has discontinued the BEACON-IPF Phase 2b trial evaluating bexotegrast in patients with idiopathic pulmonary fibrosis (IPF). While an imbalance in unadjudicated IPF-related adverse events between the treatment and placebo groups led to the discontinuation of the trial, early evidence of efficacy on the forced vital capacity (FVC) endpoint was also observed.

BEACON-IPF is the first late-stage IPF trial to be discontinued for safety while showing strong evidence of efficacy.

The Company plans to analyze the complete data from the BEACON-IPF trial and evaluate next steps for bexotegrast’s development. Once the full analysis is completed, which should provide a better understanding of the benefit risk profile and therapeutic window of bexotegrast, the Company will consider additional dose-ranging Phase 2b studies with lower doses in pulmonary fibrosis and potentially, other non-respiratory indications, including liver diseases.

https://www.globenewswire.com/news-release/2025/03/03/3035743/0/en/Pliant-Therapeutics-Provides-Update-on-BEACON-IPF-a-Phase-2b-3-Trial-in-Patients-with-Idiopathic-Pulmonary-Fibrosis.html

Aclarion First Commercial Agreement with Scripps Health

 Agreement expands access to Nociscan technology for leading spine physicians and more than 3.2M people in the greater San Diego Metro area

Nociscan leverages MR Spectroscopy (MRS) and Augmented Intelligence (AI) to Identify Sources of Chronic Low Back Pain

https://www.globenewswire.com/news-release/2025/03/03/3035378/0/en/Aclarion-Announces-First-Commercial-Agreement-with-Scripps-Health.html

BioXcel: FDA Closed Inspection of Site for Phase Alzheimer’s Dementia Trial

 FDA concludes site inspection is closed under 21 C.F.R.20.64(d)(3); Voluntary Action Indicated

Company believes this further supports reliability of data from TRANQUILITY II trial of BXCL501

https://www.globenewswire.com/news-release/2025/03/03/3035455/0/en/BioXcel-Therapeutics-Announces-FDA-Closed-its-Inspection-of-Site-for-Phase-3-TRANQUILITY-II-Trial-for-Acute-Treatment-of-Agitation-Associated-with-Alzheimer-s-Dementia.html

Zelensky Rejects Calls For Immediate Ceasefire & Won't Apologize To Trump: 'Ukraine Not For Sale'

 Ukrainian President Volodymyr Zelensky has remained defiant in the wake of Friday's explosive confrontation with President Trump and Vice President JD Vance in the Oval Office. He said from London Sunday that he will not apologize that that his country's freedom is "not for sale".

He acknowledged that the public spat "didn’t bring anything positive or additional to us as partner" - however he also said "This relationship will continue because this is more than a relationship in one moment."

Zelensky in London, AFP

"If you don’t have an end to the war and you don’t have security guarantees, no one is able to control a ceasefire," he told reporters while preparing to leave the UK, following a meeting with European leaders to agree on continued support for Ukraine.

Financial Times has underscored that Zelensky is not only rejecting calls from the US to apologize to Trump and Vance, but he's now openly pushing back against ceasefire. The Ukrainian leader...

rejected calls for Ukraine to agree an immediate ceasefire in its war with Russia, saying it would be “failure for everyone” if a cessation of hostilities were not accompanied by detailed security guarantees.

"If you don’t have an end to the war and you don’t have security guarantees, no one is able to control a ceasefire," Zelensky stressed in these latest remarks.

He still proclaimed that he remains "ready" to sign a US-Ukraine minerals deal, confirming that his aides are now speaking to Trump's team about ways to move forward on it.

Zelensky says he is prepared to sign a mineral rights deal with the US and thinks the relationship with Washington can be salvaged. —NBC

But the mood from the White House appears to be one of willingness to cut Zelensky off altogether. There are reports that President Trump is mulling cutting off all continuing defense aid to Ukraine.

Administration officials have sought to clarify that this was no ambush which played out before media cameras on Friday, but that Zelensky was rude and confrontational the whole time, and never satisfied with what the US was providing to Ukraine.

National Security Advisor Michael Waltz told the Sunday news shows that President Trump "was frustrated and angry because it’s unclear if Zelensky truly wants to stop the fighting. The President and VP said enough is enough."

Walz added: "This [lecturing] was the wrong approach, wrong time, and the wrong president to try to do this kind of a thing. This is not Joe Biden. The entire world saw that, crystal clear."

And this segment from Walz's account in a Fox News interview is hugely revealing:

Q: How did Zelensky react after press left? Was he surprised?

Waltz: No. His team was. His ambassador, and adviser were practically in tears, wanting this to move forward. But Zelensky was still argumentative. I said “Mr. President, time is not on your side here, on the battlefield, and in terms of the world situation. And most importantly, USAID, and the taxpayers' tolerance, is not unlimited”.

Waltz: I think Zelensky is used to hearing that “as long as it takes” and blank check from Biden.

He has not gotten the memo that this is a new sheriff in town. This is a new president, and we are determined to take a new approach towards peace.

European leaders are meanwhile trying to absorb the blowback and fallout, now talking about an alternative peace plan backed by "boots on the ground and planes in the air". UK Prime Minister Sir Keir Starmer is leading the way on plans for a 'stabilization force' to back a Ukraine ceasefire, likely involving France - and which the Europeans hope Trump can sign on to. But the Kremlin is likely to immediately reject it, given the Western 'boots on the ground' aspect to the plan.

https://www.zerohedge.com/geopolitical/zelensky-rejects-calls-immediate-ceasefire-wont-apologize-trump-ukraine-not-sale

US Reportedly Halts Offensive Cyber Ops Against Russia As Trump Pulls World Back From Brink

 In the latest indication that we're entering a new, less adversarial era of US-Russia relations, Defense Secretary Pete Hegseth has ordered a suspension of offensive cyber operations against Russia. 

The length of the pause is uncertain but the purpose seems clear: To demonstrate good will as the Trump administration earnestly seeks a negotiated end to the three-year-old war in Ukraine, which has been costly not only to the two warring countries, but to the United States and Western European countries that first precipitated that conflict, and then perpetuated it. The pause will continue as long as negotiations move forward, according to the Washington Post's sources. 

US officials tell various media outlets that the stand-down order was issued to US Cyber Command in late February. Headquartered at Ft Meade, Maryland and commanded by Air Force Gen. Tim Haugh, the mission of Cyber Command's two to three thousand employees is to "plan and execute global cyber operations, activities, and missions to defend and advance national interests in collaboration with domestic and international partners across the full spectrum of competition and conflict."

Created in 2010, US Cyber Command is headquartered at Fort Meade, Maryland

“I have seen many times when we are in some type of negotiation with another nation, especially if it’s one that is considered an adversary, that we stop operations, exercises, we even cancel speeches sometimes,” retired Cyber Command deputy commander Lt. Gen. Charlie Moore told the Post. 

The pause in offensive cyber-operations was first reported by The Record. 

The precise nature of the adjustment in activity is unclear, but the outlet's sources say it does not apply to the National Security Agency and its signals intelligence-gathering.  

Right on cue, hawks squawked over the deescalation move. “Russia continues to be among the top cyberthreats to the United States,” James A. Lewis, a Clinton administration diplomat and former U.N. cyber negotiator told the Washington Post. 

“Turning off cyber operations to avoid blowing up the talks may be a prudent tactical step. But if we take our foot off the gas pedal and they take advantage of it, we could put national security at risk.” Senate Minority Leader Chuck Schumer accused Trump of giving Russian President Vladimir Putin "a free pass...to launch cyberoperations and ransomware attacks against critical American infrastructure.”

Pete Hegseth talks to reporters upon arriving at the Pentagon for his first day as Secretary of Defense (PO1 Alexander Kubitza via DOD)

Appearing on ABC's This Week on Sunday, Secretary of State Marco Rubio pushed back on leftist hysterics about Trump's eagerness to reach a negotiated ceasefire and lasting peace in Ukraine -- consistent with his campaign pledges: 

“If this was a Democrat that was doing this, everyone would be saying, well, he’s on his way to the Nobel Peace Prize. This is absurd. We are trying to end a war. You cannot end a war unless both sides come to the table, starting with the Russians, and that is the point the president has made. And we have to do whatever we can to try to bring them to the table to see if it’s even possible.”

In another recent sign of easing tensions between the world's two nuclear superpowers, the United States approved Russia's selection of a new ambassador to Washington. Aside from the Ukraine peace overtures, current bilateral US-Russia dialogue has been focused on fully restoring relations and putting back in place all embassy staff in Washington and Moscow, respectively. As relations deteriorated during the Biden era, there had been several rounds of hostile, mutual booting of diplomats. Meanwhile, a summit between Trump and Putin is in the works. 

Time for the Union of Concerned Scientists to dial back its Doomsday Clock?   

https://www.zerohedge.com/geopolitical/us-halts-offensive-cyber-ops-against-russia-trump-pulls-world-back-brink