Category: 3. Business

Overview

 

Ensuring quality of the health product ensures its safety and efficacy. Manufacturers in lowand middle-income countries (LMICs) face challenges to achieve quality in local production,
such as the lack of an available manufacturing workforce trained in quality and understanding
regulatory quality standards and difficulties in implementing a quality culture in the
manufacturing facility.

The Local Production and Assistance (LPA) Unit in the Innovation and Emerging Technologies
Department (IET), Access to Medicines and Health Products Division (MHP), WHO, supports
Member States (MS), particularly LMICs, to strengthen sustainable local production and
technology transfer to improve timely, equitable access to quality, safe and effective essential
medical products. The LPA Unit provides assistance and support to MS with an ecosystem wide and holistic approach, such as conducting ecosystem assessments for sustainable,
quality local production, developing and implementing strategies, roadmaps and tools,
providing comprehensive capacity building and technical assistance, including for WHO
Prequalification (PQ)/Emergency Use Listing (EUL), and facilitating technology transfer (TT).

To support MS to overcome challenges to locally produce quality-assured vaccines and
biotherapeutics, medicines and in vitro diagnostics (IVDs), the LPA Unit organized a new
global training event – Week of Quality – to complement the annual Virtual cGMP Training
Marathons also organized by the LPA Unit. The first Week of Quality was organized from 16 to
20 June 2023 and focused on establishing quality specifications of vaccines, medicines and
IVDs based on WHO and other international guidelines, one of the stepping stones to
achieve quality. The second week of quality took place from 15 April to 13 June 2024 and
focused on exploring key aspect of regulatory compliance for Medicines, IVDs and Vaccines
and biotherapeutics. More than 1700 vaccine and biopharmaceutical manufacturers and
regulators attended the sessions on key aspects of vaccine and biotherapeutic
regulatory compliance. More than 1400 pharmaceutical manufacturers and
regulators strengthened their knowledge on quality requirements for pharmaceutical
product development.

And for the first time, over 1000 IVD manufacturers and
regulators, built capacity in principles of design, quality and compliance for optimizing IVD
product development.
Questions raised by manufacturers and regulators in the second Week of Quality have been
assembled in this training material with questions-and-answers (Q&A) with answers prepared
and peer-reviewed by experts with long and rich experience in the vaccine, medicine or IVD
industry, national regulatory authority (NRA), and other organizations. This document has
been developed to provide manufacturers and other relevant stakeholders with a continuous
learning resource and reference document to acquire new and fortify existing, knowledge
and capacities to strengthen the local production of quality vaccines, medicines and IVDs.

BTS 82-25

The U.S. Department of Transportation (DOT) today released its Airline Service Quality Performance data compiled for the month of September 2025 for on-time performance, mishandled baggage, mishandled wheelchairs, and scooters. 
 

For additional information and interactive charts on transportation’s role in aviation, please visit BTS’ Aviation Facts and Figures. BTS regularly updates TranStats, with both Marketing Carrier On-Time Performance (Beginning January 2018) and the Reporting Carrier On-Time Performance (1987-present).

To receive updates from BTS directly to your email, please consider subscribing to our GovDelivery service.

Gedatolisib plus fulvestrant (Faslodex) with or without palbociclib (Ibrance) continued to showcase significant efficacy vs fulvestrant alone when used as second-line treatment in patients with hormone receptor–positive, HER2-negative, PIK3CA wild-type advanced breast cancer, irrespective of duration of prior treatment, according to updated data from the phase 3 VIKTORIA-1 trial (NCT05501886).¹

Findings from additional analyses, which were shared during the 2025 San Antonio Breast Cancer Symposium, looked at progression-free survival (PFS) by time to progression (TTP) on immediate prior therapy. Those with a TTP longer than 6 months who received the gedatolisib triplet experienced a median PFS of 9.9 months (95% CI, 7.2-19.2) vs just 1.9 months (95% CI, 1.8-2.3) with fulvestrant monotherapy (HR, 0.20; 95% CI, 0.13-0.30; P < .0001); those given the gedatolisib doublet experienced a median PFS of 7.6 months (95% CI, 5.5-10.0; HR, 0.25; 95% CI, 0.17-0.37; P < .0001). Those with a TTP longer than 12 months who received the triplet had a median PFS of 10.7 months (95% CI, 7.2-19.2) vs 1.9 months (95% CI, 1.8-3.5) with the monotherapy (HR, 0.21; 95% CI, 0.15-0.31; P < .0001); treatment with the doublet led to a median PFS of 9.1 months (95% CI, 5.5-13.6; HR, 0.26; 95% CI, 0.18-0.37; P < .0001).

In those who had a TTP of longer than 18 months, the median PFS with the gedatolisib triplet was 12.4 months (95% CI, 7.0-19.3) compared with 1.9 months (95% CI, 1.8-3.5) with fulvestrant alone (HR, 0.17; 95% CI, 0.11-0.28; P < .0001); the median PFS with the gedatolisib doublet was 10.0 months (95% CI, 5.6-not evaluable [NE]; HR, 0.19; 95% CI, 0.12-0.31; P < .0001). Lastly, in those with a TTP of longer than 24 months who received the combination vs the monotherapy, the median PFS was 12.4 months (95% CI, 7.4-NE) vs 2.0 months (95% CI, 1.8-3.7), respectively (HR, 0.26; 95% CI, 0.26-0.28; P < .0001); with the gedatolisib doublet, the median PFS was 13.6 months (95% CI, 7.6-NE; HR, 0.14; 95% CI, 0.08-0.27; P < .0001).

“VIKTORIA-1 is the first study to demonstrate a statistically significant and clinically meaningful improvement in PFS with PAM inhibition in patients with PIK3CA wild-type disease, all of whom received prior CDK4/6 inhibition,” Barbara Pistilli, MD, the head of the Breast Cancer Unit at Gustave Roussy, in Villejuif, France, said in a rapid fire presentation of the data. “These additional analyses confirm the efficacy of gedatolisib irrespective of the duration of prior treatment.”

What was the design of the VIKTORIA-1 trial evaluating gedatolisib in this breast cancer population?

Gedatolisib at a Glance: What Updated VIKTORIA-1 Data Reveals

• Gedatolisib plus fulvestrant, with or without palbociclib, consistently improved PFS vs fulvestrant alone, regardless of prior treatment duration in patients with hormone receptor–positive, HER2-negative, PIK3CA wild-type advanced breast cancer.

• Benefit was observed in both bone-only and non–bone only metastases, with the strongest gains seen in non–bone only disease.

• Stomatitis was the most common toxicity reported on the trial but was mostly low grade and manageable.

• The median time to definitive deterioration was meaningfully delayed with gedatolisib regimens vs fulvestrant monotherapy.

The study enrolled premenopausal and postmenopausal patients with hormone receptor–positive, HER2-negative, advanced breast cancer who progressed on or following CDK4/6 inhibition and a nonsteroidal aromatase inhibitor.² Patients received no more than 2 prior lines of endocrine therapy for advanced disease, were tested for PIK3CA status, and did not have prior exposure to an mTOR inhibitor, a PI3K inhibitor, an AKT inhibitor, or chemotherapy for advanced disease.

Those with PIK3CA wild-type disease were randomly assigned 1:1:1 (n = 392) to 1 of 3 treatment arms: gedatolisib plus palbociclib and fulvestrant (arm A), gedatolisib plus fulvestrant (arm B), and fulvestrant alone (arm C). Gedatolisib was administered at a once weekly dose of 180 mg as part of a 3-weeks-on/3-weeks-off schedule; palbociclib was given at a daily dose of 125 mg for 21 days on and 7 days off; and fulvestrant was administered at 500 mg on days 1 and 15 and then every 4 weeks. Those in arm C were able cross over to arms A or B when they experienced disease progression.

Stratification factors included presence of lung or liver metastases (yes vs no), TTP on immediate prior therapy (≤6 vs >6 months), and region (US/Canada vs rest of the world).

The primary end points of the study were PFS by blinded independent central review for arm A vs arm C and for arm B vs arm C. Key secondary end points comprised overall survival (OS), objective response rate (ORR), safety, and quality of life (QOL).

What data have previously been reported from VIKTORIA-1 with the gedatolisib combinations?

Data from the primary analysis of VIKTORIA-1 presented during the 2025 ESMO Congress indicated that the gedatolisib triplet (n = 131) led to a median PFS of 9.3 months (95% CI, 7.2-16.6) vs 2.0 months (95% CI, 1.8-2.3) with fulvestrant monotherapy (n = 131), translating to a 76% reduction in the risk of disease progression or death (HR, 0.24; 95% CI, 0.17-0.35; P < .0001). The gedatolisib doublet (n = 130) led to a median PFS of 7.4 months (95% CI, 5.5-9.9), which translated to a 67% reduction in the risk of disease progression or death vs single-agent fulvestrant (HR, 0.33; 95% CI, 0.24-0.48; P < .0001).

At the time of the interim analysis, immature OS data showed that the median OS with the triplet was 23.7 months (95% CI, 21.4-NE) vs 18.5 months (95% CI, 15.8-NE) with fulvestrant alone (HR, 0.69; 95% CI, 0.43-1.12; P = .1328); the median OS with the gedatolisib doublet was not reached (NR; 95% CI, NE-NE; HR, 0.74; 95% CI, 0.46-1.19; P = .2122). Additionally, ORRs of the the triplet, doublet, and monotherapy were 31.5%, 28.3%, and 1.0%, respectively; with median duration of response of 17.5 months (95% CI, 8.8-NE), 12.0 months (95% CI, 8.1-NE), and NR (95% CI, NE-NE).

What additional efficacy data were reported from the analyses shared during SABCS?

PFS was also examined by bone metastases status.¹ Findings indicated that in those with bone-only metastases, the gedatolisib triplet led to a median PFS that was NR (95% CI, 7.0-NE) vs 8.2 months (95% CI, 1.7-NE) with fulvestrant (HR, 0.30; 95% CI, 0.04-2.37; P = .2969); the gedatolisib doublet resulted in a median PFS that was also NR (95% CI, 3.5-NE; HR, 0.41; 95% CI, 0.12-1.54; P = .2098).

In those with non–bone only metastases, the gedatolisib triplet resulted in a median PFS of 9.3 months (95% CI, 5.7-16.6) vs 1.9 months (95% CI, 1.8-2.0) with fulvestrant (HR, 0.23; 95% CI, 0.16-0.33; P < .0001); the gedatolisib doublet led to a median PFS of 7.3 months (95% CI, 5.5-9.4; HR, 0.32; 95% CI, 0.23-0.45; P < .0001).

What did additional safety analysis reveal about the gedatolisib regimens?

“Stomatitis was the most frequent adverse [effect] reported in the VIKTORIA-1 trial, and I want to remind you that the study protocol recommended prophylactic use of a steroid containing mouthwash,” Pistilli noted. “The majority of patients experienced grade 1 stomatitis as the first event.”

Treatment-related stomatitis was reported in 69.2% of those given the triplet (n = 130) and in 56.9% of those given the doublet (n = 130), and the median time to onset was 7.5 days (range, 1-259) and 4.0 days (range, 1-524), respectively. Of those in the triplet arm, 57 had a grade 1 event, 24 experienced a grade 2 event, and 9 had a grade 3 event; the median time to first onset ranged from 4.0 days (range, 1-20) to 8.0 days (range, 1-259). In the doublet arm, 48 patients experienced a grade 1, 16 had a grade 2 event, and 10 had a grade 3 event with median time to first onset ranging from 3.5 days (range, 2-87) to 4.5 days (range, 1-524).

“Most stomatitis events occurred within the first 3 weeks of treatment initiation, the majority were grade 1, and very few patients experienced grade 3 stomatitis as this event,” she said.

In the triplet arm, the median time to improvement from grade 3 to lower was 12.0 days (range, 3-103), from grade 2 to lower was 14.0 days (range, 4-229), and from grade 1 to lower was 27.5 days (range, 1-402). In the doublet arm, the median time to improvement from grade 3, grade 2, or grade 1 to lower was 7.5 days (range, 2-112), 9.0 days (range, 3-41), and 17.5 days (range, 1-317), respectively. “Grade 2/3 [effects] generally improved to a lower grade within 1 to 2 weeks,” Pistilli said.

She added that median glucose levels were stable. All-grade hyperglycemia occurred in 9.2% of those who received the triplet, 11.5% of those given the doublet, and no patients who received the monotherapy. Change in median HbA1c from baseline to end of therapy in the respective arms was 0.5 (range, –1.6 to –2.9), 0.6 (range, –0.7 to –8.2), and 0.2 (range, –0.6 to 1.3). “Gedatolisib did not produce clinically relevant hyperglycemia and had no dose reductions or withdrawals due to hyperglycemia,” Pistilli said.

What was learned in terms of PROs?

The median time to definitive deterioration in EQ-5D-5L was “meaningfully delayed” with gedatolisib vs fulvestrant,” she added. In the triplet arm the median time to definitive deterioration was 23.7 months (95% CI, 6.8-NE) vs 4.0 months (95% CI, 2.8-8.2) in the monotherapy arm (HR, 0.39; 95% CI, 0.25-0.67; P = .0003); in the doublet arm, the median time to definitive deterioration was NR (95% CI, 7.1-NE; HR, 0.37; 95% CI, 0.24-0.66; P = .0003).

What is the take-home message of the updated VIKTORIA-1 data?

“Gedatolisib plus fulvestrant, with or without palbociclib, represents a potential new standard of care for patients with hormone receptor–positive, HER2-negative, PIK3CA wild-type advanced breast cancer whose disease progressed on or after treatment with a CDK4/6 inhibitor,” Pistilli concluded.

In November 2025, a new drug application seeking approval of gedatolisib for use in patients with hormone receptor–positive, HER2-negative advanced breast cancer was submitted to the FDA for review.³ The NDA was supported by findings from the PIK3CA wild-type cohort of VIKTORIA-1.

Disclosures: Pistilli disclosed receipt of consulting fees from Astrazeneca (institutional), Seagen (institutional), Gilead (institutional), Novartis (institutional), Lilly (institutional), MSD (institutional), Pierre Fabre (personal), Daiichi Sankyo (institutional/personal), and Olema (institutional). Research funding (institutional) was provided by AstraZeneca, Daiichi Sankyo, Gilead, Seagen, and MSD. Travel support was provided by AstraZeneca, Gilead, MSD, Daiichi Sankyo, Accord, and Pfizer.

References

1. Pistilli B, Layman RM, Curigliano G, et al. Gedatolisib, a multitarget PI3K/AKT/mTOR inhibitor, plus fulvestrant with or without palbociclib for second-line treatment of patients with HR+/HER2-/PIK3CA-WT advanced breast cancer: updated results from the randomized, phase 3 VIKTORIA-1 trial. Presented at: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract R47-04.
2. Hurvitz SA, Layman RM, Curigliano G, et al. Gedatolisib plus fulvestrant, with and without palbociclib, vs fulvestrant in patients with HR+/HER2-/PIK3CA wild-type advanced breast cancer: first results from VIKTORIA-1. Presented at: 2025 ESMO Annual Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA17.
3. Celcuity announces completion of submission of its new drug application to the US FDA for gedatolisib in HR+/HER2-/PIK3CA wild-type advanced breast cancer. News release. Celcuity, Inc. November 17, 2025. Accessed December 11, 2025. https://ir.celcuity.com/press-releases/

Verra has opened a public consultation on a major revision to VM0032 Methodology for the Adoption of Sustainable Grasslands through Adjustment of Fire and Grazing, v1.0 in the Verified Carbon Standard (VCS) Program. The revised methodology would be published as VM0032 Sustainable Native Grasslands Management through Adjustment of Fire and Grazing, v2.0. The consultation will run from December 11, 2025, through January 23, 2026.

VM0032 is globally applicable and quantifies the greenhouse gas emission reductions and removals from sustainable practices that sequester carbon in soil and woody biomass and/or avoid emissions from natural fires.

The proposed revision includes the following:

• Enhanced grasslands definition
• Updated applicability conditions and specifications for project boundaries
• Updated additionality requirements
• Introduction of a modeled way of setting a baseline
• Introduction of true-up mechanism for soil organic carbon (SOC) modeling
• Introduction of control sites for SOC and woody biomass measurements
• Updates to leakage and uncertainty sections
• Updates to ensure consistency between VM0032, v2.0 and the proposed major revision to VM0042 for grazing projects implemented on pastures and rangelands, clarifying each methodology’s applicability in terms of agricultural and livestock management, land use, and land cover
• Introduction of differentiation between emission reductions and carbon dioxide removals

Verra is seeking general feedback on the proposed revisions, as well as targeted feedback on whether to keep VM0032 as a standalone methodology or integrate it into VM0042.

Option 1: VM0032 remains active, and Verra would clarify that native grasslands are not eligible under VM0042, v3.0.

Option 2:  VM0032 will be inactivated and VM0042 would be revised to include all grassland system types, i.e., all native grasslands management projects that focus on soil organic carbon stock increases would be required to use VM0042.

Verra also welcomes more specific feedback on whether projects using VM0026 (any version) or VM0032, v1.0 should be able to transition to VM0032, v2.0.

Please note that the public consultation on VM0042, v3.0 is expected to start in January 2026.

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About Collins Aerospace
Collins Aerospace, an RTX business, is a leader in integrated and intelligent solutions for the global aerospace and defense industry. Our 80,000 employees are dedicated to delivering future-focused technologies to advance sustainable and connected aviation, passenger safety and comfort, mission success, space exploration, and more.

About RTX
RTX is the world’s largest aerospace and defense company. With more than 185,000 global employees, we push the limits of technology and science to redefine how we connect and protect our world. Through industry-leading businesses – Collins Aerospace, Pratt & Whitney, and Raytheon – we are advancing aviation, engineering integrated defense systems for operational success, and developing next-generation technology solutions and manufacturing to help global customers address their most critical challenges. The company, with 2024 sales of more than $80 billion, is headquartered in Arlington, Virginia. For questions or to schedule an interview, please contact [email protected].

About Elbit Systems of America, LLC 
Elbit Systems of America, headquartered in Fort Worth, Texas, is a leading provider of high-performance products, system solutions, and support services focusing on the defense, homeland security, law enforcement, commercial aviation, and medical instrumentation markets. With facilities throughout the U.S., Elbit Systems of America is dedicated to supporting those who contribute daily to the safety and security of the United States. Elbit Systems of America, LLC is wholly owned by Elbit Systems Ltd. (NASDAQ: ESLT and TASE: ESLT), a global high technology company engaged in a wide range of programs for innovative defense and commercial applications.  For additional information, visit www.ElbitAmerica.com, or follow us on X, LinkedIn, Facebook, and YouTube.

About Elbit Systems
Elbit Systems is a leading global defense technology company, delivering advanced solutions for a secure and safer world. Elbit Systems develops, manufactures, integrates and sustains a range of next-generation solutions across multiple domains. Driven by its agile, collaborative culture, and leveraging Israel’s technology ecosystem, Elbit Systems enables customers to address rapidly evolving battlefield challenges and overcome threats. Elbit Systems employs approximately 20,000 people in dozens of countries across five continents. The Company reported $1.9 billion in revenues for the three months ending March 31, 2025, and an order backlog of $23.1 billion as of such date. For additional information, visit: https://elbitsystems.com/, follow us on Twitter, or visit our official Facebook, YouTube, and LinkedIn channels.

JPMorgan Chase is facing the ire of some of the world’s biggest investors over the bank’s role in a complex multibillion-dollar refinancing at Patrick Drahi’s telecoms group Altice USA that threatens them with heavy losses.

After the Altice deal, and an antitrust lawsuit it filed against investment groups including Apollo Global Management, Ares Management, BlackRock and Oaktree, some investors told the Financial Times they were rethinking relationships with the US bank as well as with Kirkland & Ellis, the powerhouse law firm seen as the architect of the legal complaint.

Distressed debt investors are accustomed to aggressive manoeuvring but it is unusual to see the biggest bank in the US, with $4.6tn in assets, step into a messy confrontation between a billionaire entrepreneur and aggrieved Wall Street funds.

“This is wild . . . this is the craziest thing that has happened in the history of the distressed debt market,” said the head of one prominent multi-strategy private capital fund, referring to JPMorgan’s central role in a surprise $2bn capital raise.

Altice USA had been struggling under the weight of $26bn of debt and for months had been locked in tense negotiations with its creditors. Since Altice’s creditors were unusually united, the company lacked some of the leverage it could normally exert by playing one lender off another.

But the company had another gambit. Altice was desperate to pay off one of its borrowings, known as its B-6 term loan, because it contained restrictive covenants that prevented a broader refinancing. If it could pay off the B-6 term loan, it would no longer be bound by those terms, giving it far greater flexibility to raise new debt.

Paying off the B-6 loan would also give Altice the opportunity to move some collateral — previously pledged to other lenders — outside the reach of its existing creditors.

Such a manoeuvre would be controversial. Some investors believed Altice needed separate backing from its existing lenders, which it may have struggled to obtain given they were lined up against it.

Then JPMorgan stepped into the breach. It was the administrative agent on the B-6 term loan, meaning it was responsible for managing the payment of interest and principal to lenders — and for overseeing the collateral.

JPMorgan believed it was in its own bind, according to people familiar with the matter.

The bank had been told that Altice had competing offers from private capital firms to provide the cash to pay down the B-6 loan, people familiar with the matter said, with the understanding that the replacement financing would be provided to a different subsidiary not involved in the ongoing debt fight. Collateral previously pledged under the B-6 term loan could then be moved to this new structure, away from the rest of the creditors fighting with Altice.

Rather than have someone else provide the debt backed by the shifted collateral, JPMorgan decided to step in and make the loan itself to its long-term client, one of the people added.

On November 25 Altice announced it had borrowed $2bn from the bank, money that it then used to pay down the B-6 term loan, wiping away its onerous covenants.

The reaction in the market has been explosive.

“JPMorgan has crossed a line here that I don’t know has ever been crossed before,” said a top executive at a large investment group. “And if there was going to be a bank to do it, JPMorgan would have been last to do it.”

Although such a move was not uncommon, it would normally have been a lender with a greater risk appetite willing to take on such a deal — a specialist outfit such as Apollo, Angelo Gordon or Centerbridge, for example.

Banks like JPMorgan have significant businesses advising and trading with private investment firms. Large asset managers can often pay $100mn to $200mn in total fees each year to big banks, discouraging big banks from engaging in activities that could threaten those relationships.

As the distressed debt market has come to be dominated by so-called creditor-on-creditor violence, large banks have steered clear of picking sides. Rather than become entangled in such disputes, banks have often resigned as agents or trustees on loans or bonds when a creditor fight is about to break out.

It was JPMorgan’s decision not to do this that shocked the investors.

People familiar with the bank said it had attempted to structure the deal in a way that did the least harm to lenders, including the ability to refinance the loan without a premium in the event existing lenders wanted to pitch their own loan. They added that it had not seen any damage to its relationship with investment clients.

One investor said JPMorgan was too deep in leveraged finance markets for firms to blackball.

There was a further twist to come. Hours after the JPMorgan financing was announced, Altice USA filed a novel lawsuit in New York federal court that accused hundreds of creditors of forming an illegal cartel when they organised together to negotiate against the company.

Among the named defendants was JPMorgan’s own investment management division, which has a significant stake in Altice debt.

The antitrust lawsuit had its own fallout. Kirkland & Ellis, which did not formally bring the action but is Altice USA’s longtime restructuring adviser, has come in for criticism from the asset management community over its role.

“The Altice matter has been escalated to the top of the house,” said one top industry lawyer. Senior managers at the creditor firms have had to be drafted in to help deal teams handle the lawsuit — as well as to manage nervous limited partners.

Ares, a large Altice bondholder, has been reconsidering its long-standing relationship with Kirkland and the work it brings to the firm, according to people familiar with the matter.

“Kirkland represents Altice in transactional matters and not in the litigation,” the law firm said. The litigation strategy had been developed by another firm and the lawsuit drafted “before Kirkland was ever engaged by the company”, it added.

Altice USA, Apollo, Ares, BlackRock, JPMorgan and Oaktree declined to comment.