Category: 3. Business

Linklaters has advised Unilever PLC (Unilever) and The Magnum Ice Cream Company N.V. (TMICC) on the creation of TMICC, its separation and demerger from Unilever and its listings on the Amsterdam, London and New York stock exchanges.

In one of the largest and most complex global carve-outs in recent years, Linklaters advised on the project from conception to completion, including on strategic options for the business, executing the legal and operational separation of the ice cream business in over 80 countries, and running the demerger and listing process across Amsterdam, London and New York.

The firm was the sole legal advisor on the listing of TMICC on all three stock exchanges, running a tripartite process with the Dutch Authority for Financial Markets (AFM), the UK Financial Conduct Authority (FCA), and the United States Securities and Exchange Commission (SEC) and delivering an innovative structure that will see TMICC’s ordinary shares trading on the New York Stock Exchange.

This follows a number of high-profile roles for Linklaters on Unilever’s other global carve-outs, including advising on the €4.5bn sale of its tea business to CVC Capital Partners and on the US$7bn carve-out sale of its global spreads business to KKR.

The Linklaters team, spanning 24 offices,18 countries, and 14 practices, was led by London Corporate Partners Charlie Turner and Michael Fanner, Dutch Corporate Partners Guido Portier and Alexander Harmse, US Corporate Partners Mike Bienenfeld and Igor Rogovoy, and Tax Partners Chris Smale and Michelle Lo.

Charlie Turner, Corporate Partner at Linklaters, said: 

“The depth and breadth of our global teams enabled us to deliver on one of the largest and most complex carve-outs in recent years, as well as advising on all three listings for the demerger. Our team showed great agility in navigating the complexity of the separation and competing requirements of three regulatory regimes as well as helping Unilever and The Magnum Ice Cream Company navigate the US government shutdown. Congratulations to both Unilever and The Magnum Ice Cream Company on this incredible transaction.” 

Pirtobrutinib (Jaypirca)demonstrated noninferiority in overall response rate (ORR) compared with ibrutinib (Imbruvica) in patients with BTK inhibitor–naive chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) in both the relapsed/refractory (R/R) and treatment-naive settings, according to findings from the phase 3 BRUIN CLL-314 trial (NCT05254743). The results from this head-to-head comparison also showed a progression-free survival (PFS) trend in favor of pirtobrutinib, according to Jennifer Woyach, MD, who presented the findings at the 2025 ASH Annual Meeting.¹

In the ITT population of patients with either R/R or treatment-naive CLL/SLL, the ORR was 87% in patients randomized to pirtobrutinib (n = 331) vs 78.5% in those randomized to ibrutinib (n = 331; P = .0035). The ORR ratio was 1.1080 (95% CI, 1.034–1.187; P value for noninferiority <.0001). The best overall response with pirtobrutinib vs ibrutinib, respectively, was complete remission (CR) or CR with incomplete hematologic recovery (CRi) of 4.8% vs 2.4%, partial remission (PR) or nodular partial remission (nPR) of 82.2% vs 76.1%, partial remission with lymphocytosis (PR-L) of 2.4% vs 3.9%, stable disease (SD) of 5.4% vs 10.9%, and progressive disease (PD) of 1.5% vs 1.2%.

In the treatment-naive population, the ORR was 92.9% in patients randomized to pirtobrutinib (n = 112) vs 85.8% in those randomized to ibrutinib (n = 113; P = .0886). The ORR ratio was 1.0797 (95% CI, 0.989–1.179). The best overall response with pirtobrutinib vs ibrutinib, respectively, was CR/CRi of 7.1% vs 3.5%, PR/nPR of 85.7% vs 82.3%, PR-L of 0.9% vs 2.7%, SD of 2.7% vs 4.4%, and no cases of PD.

In the R/R population, the ORR was 84.0% in patients randomized to pirtobrutinib (n = 219) vs 74.8% in those randomized to ibrutinib (n = 218; P = .0886). The ORR ratio was 1.1233 (95% CI, 1.020–1.237; P value for noninferiority <.0001). The best overall response with pirtobrutinib vs ibrutinib, respectively, was CR/CRi of 3.7% vs 1.8%, PR/nPR of 80.4% vs 72.9%, PR-L of 3.2% vs 4.6%, SD of 6.8% vs 14.2%, and PD of 2.3% vs 1.8%

“Pirtobrutinib demonstrated consistently higher ORR than ibrutinib across all patients, including treatment-naive and R/R populations,” said Woyach, director of the Division of Hematology, The Ohio State University Comprehensive Cancer Center.

PFS data, while immature, showed a trend in favor of pirtobrutinib. In the ITT population, at a median follow-up of 22.0 months with pirtobrutinib and 19.7 months with ibrutinib, the 18-month PFS rates per investigator assessment were 86.9% vs 82.3%, respectively (HR, 0.569; 95% CI 0.388–0.834; nominal P value = .0034). In the R/R population, at a median follow-up of 18.4 months with pirtobrutinib and 15.8 months with ibrutinib, the investigator-assessed 18-month PFS rates were 81.7% vs 79.2%, respectively (HR, 0.729; 95% CI, 0.471–1.128; nominal P value =.1563). And in the treatment-naive population, at a median follow-up of 22.5 months with pirtobrutinib and 22.4 months with ibrutinib, the investigator-assessed 18-month PFS rates were 95.3% vs 87.6%, respectively (HR, 0.239; 95% CI, 0.098–0.586; nominal P value =.0007).

“Early trends in PFS favored pirtobrutinib among all patients and in the R/R and treatment-naive populations,” said Woyach, adding that, “The most pronounced effect [was] in the treatment-naive population, which had the longest follow-up at this data cutoff.”

Safety in BRUIN CLL-314

Regarding safety, the most common all grade treatment-emergent adverse events (TEAEs) with pirtobrutinib vs ibrutinib were neutropenia (22.7% vs 17.8%), upper respiratory tract infection (17.9% vs 19.4%), anemia (15.2% vs 14.2%), pneumonia (13.6% vs 15.1%), and diarrhea (13.3% vs 19.1%). The most common grade ≥3 TEAEs with pirtobrutinib vs ibrutinib were mostly similar: neutropenia (17.3% vs 13.2%), pneumonia (6.4% vs 8.6%), anemia (5.8% vs 3.7%).

Rates of all-grade (10.6% vs 15.1%) and grade ≥3 (3.3% vs 4.9%) hypertension were lower with pirtobrutinib vs ibrutinib. One patient developed Richter Transformation with pirtobrutinib vs 4 patients with ibrutinib.

“Pirtobrutinib was well tolerated with fewer dose reductions and discontinuations due to TEAEs than ibrutinib,” said Woyach.

She said that adverse events of special interest were mostly low-grade and consistent with prior studies of pirtobrutinib. Grade ≥3 neutropenia (25.2% vs 17.5%) and anemia (6.1% vs 3.7%) were higher with pirtobrutinib vs ibrutinib; however, grade ≥3 thrombocytopenia was lower with pirtobrutinib (3.6% vs 4.0%).

All-grade incidence of atrial fibrillation/flutter (2.4% vs 13.5%) was substantially lower with pirtobrutinib versus ibrutinib, particularly among patients aged ≥75 years (4.5% vs 21.4%).

BRUIN CLL-314 Design and Patient Characteristics

The phase 3 BRUIN CLL-314 study accrued patients with BTK inhibitor–naïve CLL/SLL, including both patients with treatment-naive and R/R disease. Overall, there were 662 patients (ITT population) randomized in a 1:1 ratio to pirtobrutinib (n = 331) or ibrutinib (n = 331) between August 18, 2022, and June 17, 2024. The median age was 67 years in both the pirtobrutinib (range, 39–90) and ibrutinib (range, 34–86) arms, and the median number of prior therapies in both arms was 1. In the ITT population, 225 patients were treatment-naive and 437 patients were R/R.

In patients with evaluable samples, 68% (n = 199/293) vs 66% (n = 183/277) of patients in the pirtobrutinib vs ibrutinib cohorts had unmutated IGHV. Further, 40% (n = 104/259) vs 34% (n = 78/227) and 15% (n = 50/331) vs 16% (n = 52/331) had complex karyotype ≥3 abnormalities and del(17p), respectively.

Pirtobrutinib was administered orally at 200 mg/daily and ibrutinib was administered orally at 420 mg/daily. The primary end point was non-inferiority of ORR in the ITT population or R/R population. The key secondary end point was superiority of PFS in the ITT population or R/R population.

Significance and Next Steps

CLL-314 is the first trial comparing pirtobrutinib and ibrutinib in treatment-naive patients and patients with BTK inhibitor–naive R/R CLL/SLL.

Pirtobrutinib is currently approved by the FDA for patients with R/R CLL/SLL who have previously received a BTK inhibitor.² When the PFS data from the BRUIN CLL-314 study fully mature, it is hoped that the trend favoring pirtobrutinib will be upheld and can lead to a regulatory filing for use of the agent in earlier CLL/SLL lines.

REFERENCES

1. Woyach J, Qiu L, Grosicki S, et al. Pirtobrutinib vs ibrutinib in treatment-naïve and relapsed/refractory CLL/SLL: Results from the first randomized phase III study comparing a non-covalent and covalent BTK inhibitor. Blood. 2025;146(suppl 1): 683. doi:10.1182/blood-2025-683

2. FDA grants traditional approval to pirtobrutinib for chronic lymphocytic leukemia and small lymphocytic lymphoma. Food and Drug Administration. Published December 3, 2025. Accessed December 7, 2025. https://tinyurl.com/46522682

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The ESMO Asia 2025 Congress took place from December 5–7, 2025, at the Suntec Singapore Convention & Exhibition Centre in Singapore. The three-day meeting brought together oncology professionals from across the Asia-Pacific region to review the latest advances in cancer research and clinical practice.

The scientific program featured plenary lectures, expert sessions, and multidisciplinary tumor boards that highlighted progress in systemic therapies, immuno-oncology, precision medicine, and supportive care. Attendees also engaged in discussions on evolving treatment standards and regional challenges in oncology.

20 Posts Not to Miss from ESMO Asia 2025

In this article, we selected 20 key posts you shouldn’t miss, capturing the most impactful insights, research updates, and expert perspectives shared throughout ESMO Asia 2025.

Herbert Loong, MBBS, FASCO:

“Kicking off activities at ESMOAsia25 with a short talk on AI driven Biomarkers and what are the potentials and implications of these in drug development and oncology clinical care. A shoutout to the just released EBAI guidance document: check it out here: https://doi.org/10.1016/j.annonc.2025.11.009 Ben Westphalen and many others”

Melvin LK CHUA:

“ESMO Asia 25 Packed room for Radiation Oncology session! Such a strong line up of speakers!”

Teresa Amaral MD:

“The ESMOAsia25 ongoing patient engagement summit
Excellent discussion with patient advocates, listening and learning about the challenges patients and caregivers are facing this part of the globe .
A proud moment to see the ESMO – European Society for Medical Oncology ISF EISF project on Health Equity & hashtag#Inclusive Research PG.
You can read more about this here  https://lnkd.in/d4c43_2p

Tomorrow I will talk about “Advancing diversity in clinical trials: how Europe is meeting the challenge” and I am looking forward to a lively discussion.
Thank you to the ESMO Public Policy for the invitation.”

 Angela Lamarca:

“Very interesting discussion on toxicity Higher (x2-3 times ) haemato-toxicity (grade 1/2) in China (LUMINET-1 1) vs Western (NETTER-1 2) Should dose be the same? Maybe not (I agree Dr Llang) Stephen Chan (as ussual)”

 

Hongcheng Zhu:

“Super engaged ESMOYOC session of ESMOAsia25 with Vesalius talk about Research, Education, & Collaboration for YoungOncologists in Asia-Pacific, fantastic discussion with our amazing international experts.”

Herbert Loong, MBBS, FASCO:

“Amazing team at the educational session for lung cancer during ESMOAsia25! ”

Jarushka Naidoo:

“ESMOAsia2025 Investigator-initiated 1L Ph II/III trial Crizotinib+Chemo v Criz in ALK+ NSCLC Tata Memorial – study stopped early – DCR 55% v 75% in favour of Criz – 11SAEs 8 deaths- sepsis main tox A cautionary tale- more is not always more.”

Angela Lamarca:

“Here we are, a few of the GI people at ESMOAsia25 It’s always a pleasure working with you all Great co-chairing of the #ESMOAsia conference, Fantastic track chairs, Lorenza Rimassa and Dr Ikeda To many more of these…”

Foo Chuan Jie:

“Challenges and opportunities of oncology early-phase drug development programmes in Asia. ESMOAsia25 day2. Exciting discussions with Prof. Toshio Shimizu and Adj. Prof. Voon Pei Jye! for Phase 1!”

Jarushka Naidoo:

“ESMOAsia2025 Lung Orals MARIPOSA: Asian subgroup analysis – HR OS 0.74 – majority of MARIPOSA made up of asian subset – similar tox signal, & crossing of curves at 9m.”

Angela Lamarca:

“Proffered Paper in BTC at ESMOAsia25  TOURMALINE (DurvaChemo nonTOPAZ) in #Asia (90 pts) iCCA51%; GBC30%; PS2 16.7% 52% G3-4 AEs – haem/cholangitis; 13% anyG imAE; 6.7% IRR 26.7% ORR – best CisGem (PS2; ORR 50%) Confirms data in Asia Doublet (vs mono) chemo best.”

Yuichiro Kikawa, MD, PhD:

“Korea NHIS breast cancer: ~12% of rural pts traveled to Seoul. Travelers were younger/healthier, treated at tertiary centers, but had longer waits. Survival improved overall vs rural care (HR ~0.75); no clear benefit when initial tx was chemo. Avoid >30-day delays.”

Deborah Mukherji:

“Excellent discussion in the GU Mini Oral session this morning ESMOAsia25 thoughtfully putting new data into clinical context and highlighting what it means for real-world practice across Asia. Great insights from Dr Senthil Rajappa”

Jordi Remon:

“Uncommon / PACC EGFR mut NSCLC are 10% of all EGFRm.Afatinib is the unique drug approved in this subset. Enozertinib (ORIC-114):promising activity in PACC EGFRm in 3L with intracranial activity Other “competitors” : furmonertinib, zipalertinib, amivantamab+lazertinib”

Herdee Luna:

“Congratulations Annie Wong and the whole ESMO Asia LGP family who contributed to this abstract on APAC Availability, OPC, and Accessibility of AntiNeoplastic Medicines!”

Deborah Mukherji:

“Patient-reported data are essential to understanding real gaps in cancer care. IKCC GPS 2025 shows that SDM remains limited across Asia and up to 92% of kidney cancer patients face treatment barriers. Listening to patients must guide action.”

 Yuichiro Kikawa, MD, PhD:

“Proud to share our study from Japan’s phase 3 RESQ trial estimating MIDs for EORTC QLQ-C30/BR23 in HER2− metastatic BC. First MID estimates for QLQ-BR23 Expanded QLQ-C30 benchmarks Excellent presentation by Dr. Aoyama—clear and impactful.”

Lorenza Rimassa:

“Meet the expert: ESMO GI Oncology Journal in Asia. Su Pin Choo moderates Florian Lordick discussing gastric cancer and claudin 18.2 in Asia at ESMOAsia25 in Singapore”

Long Nguyen:

“Glad to see an increasing representation of Vietnamese young oncologist at major international oncology meetings! ESMOASIA25”

 

Foo Chuan Jie:

“Challenges and opportunities of oncology early-phase drug development programmes in Asia. ESMOAsia25 day2. Exciting discussions with Prof. Toshio Shimizu and Adj. Prof. Voon Pei Jye! for Phase 1!”

More post about ESMO Asia 2025 on OncoDaily.

MakeMyTrip (MMYT) has quietly slipped over the past month, even as its long term returns still look strong. That mix of short term weakness and solid growth makes the stock worth a closer look.

See our latest analysis for MakeMyTrip.

The latest 30 day share price return of negative 5.6 percent and 90 day share price return of negative 26.5 percent show momentum has clearly cooled, even though the five year total shareholder return of about 183 percent still points to a strong long term story.

If MakeMyTrip has put travel on your radar, it could be a good moment to explore other potential movers among high growth tech and AI stocks that are shaping the next leg of market growth.

With revenue and profits still climbing fast and the share price well below analyst targets, should investors view MakeMyTrip as a rare undervalued growth story, or has the market already priced in its next chapter of expansion?

With MakeMyTrip last closing at $73.69 against a narrative fair value of $111.90, the story leans firmly toward upside potential grounded in growth.

Ongoing investment in product innovation, particularly in AI powered personalization and user experience improvements, positions MakeMyTrip for higher conversion rates, better customer retention, and ultimately supports expanding net margins through improved operating leverage.

Read the complete narrative.

Curious how faster bookings, richer add ons, and widening margins can still justify a premium multiple for a travel platform, not a software giant? Unlock the full playbook driving that bold fair value call.

Result: Fair Value of $111.90 (UNDERVALUED)

Have a read of the narrative in full and understand what’s behind the forecasts.

However, persistent competition and structurally high marketing costs could pressure margins and quickly undermine the case for a sustained premium valuation.

Find out about the key risks to this MakeMyTrip narrative.

Zooming out from the narrative fair value, MakeMyTrip looks far less forgiving on traditional price to earnings numbers. The stock trades at about 91.6 times earnings, versus a fair ratio of 36.1 times and roughly 21 times for both the US Hospitality industry and peer group.

That gap suggests investors are already paying a steep premium for growth, leaving less room for error if forecasts slip or sentiment turns more cautious. How comfortable are you underwriting that kind of valuation stretch?

See what the numbers say about this price — find out in our valuation breakdown.

If this take does not quite match your view, or you would rather dig into the numbers yourself, you can build a personalized thesis in minutes: Do it your way.

A great starting point for your MakeMyTrip research is our analysis highlighting 2 key rewards and 2 important warning signs that could impact your investment decision.

If MakeMyTrip has sparked your interest, do not stop here. Use the Simply Wall St Screener to uncover fresh, data driven ideas before the crowd catches on.

This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned.

Companies discussed in this article include MMYT.

Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email editorial-team@simplywallst.com

Halozyme Therapeutics (HALO) has been quietly resetting expectations, with the stock up about 32% this year but slipping over the past month and past 3 months. This has prompted a fresh look at its valuation.

See our latest analysis for Halozyme Therapeutics.

At a share price of $63.33, Halozyme’s strong year-to-date share price return of around 32% contrasts with a softer recent patch, where shorter term share price returns suggest momentum has cooled even as long-term total shareholder returns remain solid.

Given that backdrop, it can be worth scanning beyond a single name and exploring healthcare stocks for other healthcare stocks that fit your view on growth, risk, and valuation.

With Halozyme still trading at a discount to analyst price targets despite solid profitability and steady growth, the key question now is whether the market is underestimating its earnings power or is already pricing in the next leg of expansion.

With Halozyme Therapeutics last closing at $63.33 against a narrative fair value of $76, the story centers on whether earnings execution can close that gap.

The broadening market for biologic therapies, driven by an aging global population and increased incidence of chronic diseases, is materially expanding the addressable market for Halozyme’s partners’ therapies. With multiple new indication approvals (e.g., DARZALEX in smoldering multiple myeloma, VYVGART Hytrulo in CIDP) and expanding TAM, Halozyme is poised for durable, high-margin royalty revenue growth as partner drugs are increasingly prescribed to new patient populations.

Read the complete narrative.

Want to see how fast growing royalties, rising margins, and shrinking share count are woven into one cohesive valuation story? The key twists sit inside this narrative, including the earnings power it expects Halozyme to reach and the lower future multiple it still assumes the market will accept. Curious how those moving parts add up to a higher fair value than today’s price suggests? Read on to unpack the full playbook behind that upside case.

Result: Fair Value of $76 (UNDERVALUED)

Have a read of the narrative in full and understand what’s behind the forecasts.

However, this upside still hinges on smooth execution, with ongoing patent litigation and concentrated royalty exposure both capable of quickly denting that optimistic earnings path.

Find out about the key risks to this Halozyme Therapeutics narrative.

If you see the story differently or want to stress test these assumptions with your own inputs, you can build a custom view in just minutes, Do it your way

A great starting point for your Halozyme Therapeutics research is our analysis highlighting 5 key rewards and 1 important warning sign that could impact your investment decision.

Before you move on, set yourself up for the next great opportunity by using the Simply Wall St Screener to uncover high quality stocks that match your strategy.

• Capture early stage growth potential by reviewing these 3573 penny stocks with strong financials that already show robust balance sheets and healthier fundamentals than most in their price range.

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• Lock in stronger long term value by scanning these 15 dividend stocks with yields > 3% that combine attractive income streams with business models built for durability across market cycles.

This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned.

Companies discussed in this article include HALO.

Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email editorial-team@simplywallst.com

– 94% of patients (51 of 54) remained free from the burden of continuous prophylaxis treatment through five years following a single infusion of HEMGENIX, demonstrating sustained therapeutic benefit
– At year five, mean factor IX activity levels remained strong at 36.1% and HEMGENIX continued to demonstrate a favorable safety profile, reinforcing its durable efficacy
– More than 75 individuals across eight countries have received HEMGENIX in real-world settings, reflecting growing global adoption

KING OF PRUSSIA, Pa., Dec. 7, 2025 /PRNewswire/ — Global biopharma leader CSL (ASX:CSL; USOTC:CSLLY) today announced five-year (60-month) results from the pivotal Phase 3 HOPE-B study, confirming the long-term durability and safety of a one-time infusion of HEMGENIX^® (etranacogene dezaparvovec-drlb) in adults living with hemophilia B. Published in the New England Journal of Medicine (NEJM) and presented simultaneously at the American Society of Hematology (ASH) Annual Meeting, the data reaffirm HEMGENIX’s consistent performance over time to deliver durable factor IX activity levels, sustained bleed protection compared to prophylaxis treatment, and continued freedom from routine prophylaxis. HEMGENIX remains the only commercially available gene therapy for adults with hemophilia B and can be used in patients with or without AAV5 neutralizing antibodies.

“The five-year HOPE-B results mark a pivotal milestone for gene therapy, providing clear, long-term data of the ability of HEMGENIX to potentially transform care for adults with hemophilia B,” said Steven Pipe, MD, Professor of Pediatrics and Pathology, Hemophilia and Coagulation Disorders Program and the Special Coagulation Laboratory, University of Michigan. “For those who have relied on frequent prophylactic infusions, achieving lasting bleed control from a single treatment offers the potential for greater day-to-day freedom and a life less burdened by the demands of ongoing therapy.”

In the Phase 3, open-label, single-dose, single-arm HOPE-B trial, 54 adult male participants with severe or moderately severe hemophilia B, with or without preexisting AAV5 neutralizing antibodies, were infused with a single dose of HEMGENIX. Of the 54 participants, 50 completed five years of follow-up. The five-year follow-up analysis demonstrated:

• Durable Factor IX Activity: Mean factor IX activity levels were sustained at greater than 36% during years one through five post-infusion: mean factor IX levels of 41.5 IU/dL (n=50) at year one, 36.7 IU/dL (n=50) at year two, 38.6 IU/dL (n=48) at year three, 37.4 IU/dL (n=47) at year four, and 36.1 IU/dL (n=48) at year five.
• Sustained Bleed Protection: The mean adjusted annualized bleeding rate (ABR) for all bleeds was reduced by approximately 90% from the lead-in (4.16, n=54) compared to year five (0.40, n=51) post-infusion. Additionally, joint bleeds were reduced by 93% from lead-in (mean ABR of 2.34 at lead-in to 0.16 at year five) and spontaneous bleeds were reduced by 94% (mean ABR of 1.52 during lead-in versus 0.09 during year five).
• Freedom from Prophylaxis: 94% of patients remained free of continuous prophylaxis treatment following their one-time gene therapy infusion. This rate has remained consistent over time, with only one participant resuming continuous factor IX prophylaxis at month 30 post-infusion.
• Favorable Safety Profile: No serious adverse events were related to treatment with HEMGENIX. HEMGENIX was generally well-tolerated, with a total of 100 treatment-related adverse events (TRAEs), most of which occurred in the first four months post-infusion. Only five TRAEs were reported between years four and five. The most common adverse events were an increase in alanine transaminase (ALT), for which nine (16.7%) participants received supportive care with reactive corticosteroids for a mean duration of 81.4 days (standard deviation: 28.6; range: 51-130 days).

“We are incredibly proud to share the five-year results from the HOPE-B study, which reinforce the lasting impact of HEMGENIX as a one-time treatment option for adults with hemophilia B,” said Deborah Long, MD, FCCP, Senior Vice President and Head, Medical Affairs, CSL. “These results highlight the meaningful difference HEMGENIX can make—helping people experience fewer bleeds compared to prophylaxis treatment and freeing them from the burden of regular ongoing treatment. We remain committed to expanding access to this important treatment.”

Although the five-year data mark the final analysis for the HOPE-B study, participants who consent will continue to be monitored in the IX-TEND 222-3003 extended follow-up study (NCT05962398), which will track patients for up to 15 years post-treatment.

The multi-year clinical development of HEMGENIX was led by uniQure (Nasdaq: QURE) and sponsorship of the clinical trials transitioned to CSL after it licensed global rights to commercialize the treatment. CSL also established a post-marketing registry to generate additional long-term safety, efficacy and durability data.

HEMGENIX has received regulatory approval in the United States, Canada, the UK, Switzerland, Australia, Saudi Arabia, Taiwan, South Korea, Singapore, and Hong Kong, and conditional marketing authorization from the European Commission (EC) for the European Union and European Economic Area. To date, more than 75 individuals across eight countries have received HEMGENIX in real-world settings.

For more information on HEMGENIX, please visit www.Hemgenix.com.

About the Pivotal HOPE-B Trial
The pivotal Phase 3 HOPE-B trial is an ongoing, multinational, open-label, single-arm study to evaluate the safety and efficacy of HEMGENIX. Fifty-four adult male participants with severe or moderately severe hemophilia B, with or without preexisting AAV5 neutralizing antibodies, were enrolled in a prospective, six-month or longer observational period during which time they continued to use their current standard-of-care therapy to establish a baseline ABR. After at least the six-month lead-in period, patients received a single intravenous administration of HEMGENIX at a 2×10^13 gc/kg dose. Patients were not excluded from the trial based on preexisting neutralizing antibodies (NAbs) to AAV5.

A total of 54 patients received a single dose of HEMGENIX in the pivotal trial, with 50 patients completing five years of follow-up. The primary endpoint in the pivotal HOPE-B study was ABR 52 weeks after achievement of stable factor IX expression (months seven to 18) compared with the six-month lead-in period. For this endpoint, ABR was measured from month seven to month 18 after infusion, ensuring the observation period represented a steady-state factor IX transgene expression. Secondary endpoints included assessment of factor IX activity.

No serious treatment-related adverse reactions (TRAEs) were reported. Two deaths occurred during the study due to non-treatment-related TRAEs: one at approximately 15 months post-dose due to cardiogenic shock and urosepsis, and another at approximately 54 months post-dose due to cardiac amyloidosis. A serious adverse event of myelodysplastic syndrome was initially assessed by the investigator as possibly treatment-related; however, following the results of molecular analysis and based on the assessment of risk factors, the investigator reassessed the event as not treatment-related after the five-year clinical database lock for the study. No inhibitors to factor IX were reported.

About Hemophilia B
Hemophilia B is a life-threatening rare disease caused by a mutation on the F9 gene, resulting in low levels of functional clotting factor IX. People with the condition are particularly vulnerable to bleeds in their joints, muscles, and internal organs, leading to pain, swelling, and joint damage. Treatments for moderate to severe hemophilia B typically include life-long prophylactic infusions of factor IX to temporarily replace or supplement low levels of the blood-clotting factor. Beyond the physical burden, many people with hemophilia B are continually confronted with the mental and emotional impact of managing their condition—and rarely have their minds free of hemophilia.

About HEMGENIX
HEMGENIX is a gene therapy that reduces the rate of abnormal bleeding in eligible people with hemophilia B by enabling the body to continuously produce factor IX, the deficient protein in hemophilia B. It uses AAV5, a non-infectious viral vector, called an adeno-associated virus (AAV). The AAV5 vector carries the Padua gene variant of Factor IX (FIX-Padua) to the target cells in the liver, generating factor IX proteins that are 8x more active than normal. These genetic instructions remain in the target cells, but generally do not become a part of a person’s own DNA. Once delivered, the new genetic instructions allow the cellular machinery to produce stable levels of factor IX.

Important Safety Information (ISI)

What is HEMGENIX?
HEMGENIX^®, etranacogene dezaparvovec-drlb, is a one-time gene therapy for the treatment of adults with hemophilia B who:

• Currently use Factor IX prophylaxis therapy, or
• Have current or historical life-threatening bleeding, or
• Have repeated, serious spontaneous bleeding episodes.

HEMGENIX is administered as a single intravenous infusion and can be administered only once.

What medical testing can I expect to be given before and after administration of HEMGENIX?
To determine your eligibility to receive HEMGENIX, you will be tested for Factor IX inhibitors. If this test result is positive, a retest will be performed 2 weeks later. If both tests are positive for Factor IX inhibitors, your doctor will not administer HEMGENIX to you. If, after administration of HEMGENIX, increased Factor IX activity is not achieved, or bleeding is not controlled, a post-dose test for Factor IX inhibitors will be performed.

HEMGENIX may lead to elevations of liver enzymes in the blood; therefore, ultrasound and other testing will be performed to check on liver health before HEMGENIX can be administered. Following administration of HEMGENIX, your doctor will monitor your liver enzyme levels weekly for at least 3 months. If you have preexisting risk factors for liver cancer, regular liver health testing will continue for 5 years post-administration. Treatment for elevated liver enzymes could include corticosteroids.

What were the most common side effects of HEMGENIX in clinical trials?
In clinical trials for HEMGENIX, the most common side effects reported in more than 5% of patients were liver enzyme elevations, headache, elevated levels of a certain blood enzyme, flu-like symptoms, infusion-related reactions, fatigue, nausea, and feeling unwell. These are not the only side effects possible. Tell your healthcare provider about any side effect you may experience.

What should I watch for during infusion with HEMGENIX?
Your doctor will monitor you for infusion-related reactions during administration of HEMGENIX, as well as for at least 3 hours after the infusion is complete. Symptoms may include chest tightness, headaches, abdominal pain, lightheadedness, flu-like symptoms, shivering, flushing, rash, and elevated blood pressure. If an infusion-related reaction occurs, the doctor may slow or stop the HEMGENIX infusion, resuming at a lower infusion rate once symptoms resolve.

What should I avoid after receiving HEMGENIX?
Small amounts of HEMGENIX may be present in your blood, semen, and other excreted/secreted materials, and it is not known how long this continues. You should not donate blood, organs, tissues, or cells for transplantation after receiving HEMGENIX.

Please see full prescribing information for HEMGENIX.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

You can also report side effects to CSL Behring’s Pharmacovigilance Department at 1-866-915-6958. 

About CSL
CSL (ASX:CSL; USOTC:CSLLY) is a leading global biopharma company with a dynamic portfolio of lifesaving medicines, including those that treat hemophilia and immune deficiencies, vaccines to prevent influenza, and therapies in iron deficiency, dialysis and nephrology. Since our start in 1916, we have been driven by our promise to save lives using the latest technologies. Today, CSL – including our three businesses, CSL Behring, CSL Seqirus, and CSL Vifor – provides lifesaving products to patients in more than 100 countries and employs 29,000+ people. Our unique combination of commercial strength, R&D focus and operational excellence enables us to identify, develop, and deliver innovations so our patients can live life to the fullest. For inspiring stories about the promise of biotechnology, visit CSL.com/Vita. 

For more information about CSL, visit CSL.com.

Media Contacts
Etanjalie Ayala, CSL
Mobile: +1 610 297 1069
Email: [email protected]

Stephanie Fuchs, CSL
Mobile: +49 151 58438860
Email: [email protected]

SOURCE CSL

Amivantamab-vmjw is a first-in-class, fully human bispecific antibody that targets epidermal growth factor receptor (EGFR) and mesenchymal–epithelial transition factor (MET). It represents one of the most significant therapeutic advances for patients with EGFR-driven non–small cell lung cancer (NSCLC), particularly those with tumors harboring EGFR exon 20 insertion mutations, a population historically characterized by aggressive disease biology and resistance to conventional EGFR tyrosine kinase inhibitors (TKIs). Since its accelerated FDA approval in 2021, amivantamab has rapidly expanded its clinical footprint, supported by robust data from multiple landmark trials, including CHRYSALIS, PAPILLON, and MARIPOSA.

Read About Non-Small Cell Lung Cancer on OncoDaily

Mechanism of Action: Dual Targeting of EGFR and MET

Amivantamab is a bispecific IgG1 antibody engineered to bind the extracellular domains of both EGFR and MET. By doing so, it simultaneously blocks ligand-dependent signaling in both pathways, induces receptor degradation, and engages immune effector functions such as antibody-dependent cellular cytotoxicity (ADCC) (Park et al., 2021). The dual inhibition is critical, because MET amplification and MET-dependent bypass signaling frequently mediate resistance to EGFR TKIs, particularly osimertinib. Amivantamab’s ability to target both receptors allows it to counteract multiple mechanisms of primary and acquired resistance.

Structural studies demonstrate that amivantamab uniquely binds to the extracellular portion of EGFR, unlike TKIs that interact with the intracellular kinase domain (Yun et al., 2023). This extracellular binding enables activity against EGFR exon 20 insertions, where steric hindrance limits TKI efficacy.

Clinical Evidence Supporting Amivantamab

CHRYSALIS: First Evidence Leading to FDA Approval

The CHRYSALIS Phase I study established amivantamab as the first approved therapy specifically for EGFR exon 20 insertion–positive NSCLC. In 81 patients previously treated with platinum chemotherapy, amivantamab demonstrated an overall response rate (ORR) of 40%, with a median duration of response (mDOR) of 11.1 months, and a median progression-free survival (mPFS) of 8.3 months (Park et al., 2021). These outcomes significantly exceeded historical data for standard chemotherapy and single-agent TKIs in this population, where ORRs typically ranged from 3% to 12%.

Infusion-related reactions (IRRs) occurred in approximately 66% of patients, almost exclusively during the first infusion, and were manageable with premedication and split dosing. Other common adverse events included rash, paronychia, and hypoalbuminemia.

CHRYSALIS-2: Activity After Osimertinib and Chemotherapy

CHRYSALIS-2 extended the evidence base to patients previously treated with both osimertinib and platinum chemotherapy—one of the most difficult groups to treat. The study reported a 37% ORR, a median PFS of 4.9 months, and durable responses in a heavily pretreated cohort (Johnson et al., 2023). These findings supported amivantamab’s potential role in post-TKI, post-chemotherapy resistance settings.

PAPILLON: Amivantamab + Chemotherapy in First-Line EGFR Exon 20 Insertion NSCLC

The PAPILLON Phase III trial changed the treatment landscape by demonstrating significant benefit for amivantamab combined with carboplatin-pemetrexed in the first-line setting. The combination produced a median PFS of 11.4 months, nearly doubling outcomes compared with chemotherapy alone (6.7 months), with a hazard ratio for progression or death of 0.40 (Sabari et al., 2023). The ORR also improved substantially, confirming the synergistic effect of antibody-targeted inhibition with cytotoxic chemotherapy.

These results position amivantamab-based regimens as the preferred first-line therapy for EGFR exon 20 insertion NSCLC in major treatment guidelines (NCCN, 2024).

MARIPOSA: Amivantamab + Lazertinib vs Osimertinib

The MARIPOSA Phase III trial evaluated the combination of amivantamab with lazertinib, a third-generation EGFR TKI, in treatment-naïve common EGFR-mutated NSCLC (ex19del or L858R). The study demonstrated superior PFS of 23.7 months versus 16.6 months with osimertinib, with a hazard ratio of 0.70 (Johnson et al., 2024). Importantly, intracranial activity was preserved, and the combination reduced the emergence of MET-driven resistance.

This is the first trial to outperform osimertinib in the first-line setting, marking the beginning of a new era in EGFR-mutant NSCLC.

Read About MARIPOSA Trial on OncoDaily

MARIPOSA-2: Post-Osimertinib Setting

MARIPOSA-2 evaluated two combinations—amivantamab plus lazertinib, and amivantamab plus chemotherapy—in patients who progressed on first-line osimertinib. Both regimens significantly improved PFS compared with chemotherapy alone. The amivantamab + chemotherapy regimen achieved PFS of ~8.3 months versus 4.2 months with chemotherapy alone, cutting the risk of progression by ~50%. This is a population for whom historical options were limited to single-agent chemotherapy with poor outcomes.

Safety Profile

Amivantamab’s safety profile is consistent across trials. IRRs, skin toxicity (acneiform rash, paronychia), hypoalbuminemia, and peripheral edema are the most frequent adverse events. These reflect EGFR and MET pathway inhibition. Discontinuation rates remain low, underscoring its tolerability even when combined with chemotherapy or TKIs.

Future Directions and Ongoing Research

Amivantamab is currently being studied in:

• Combination regimens with lazertinib (MARIPOSA-3)
• Neoadjuvant and adjuvant therapy for early-stage NSCLC
• Combinations with antibody-drug conjugates (ADCs) to deepen response rates
• Trials targeting resistance mechanisms after osimertinib and amivantamab failure

Preclinical data suggest amivantamab may sensitize tumors to MET-TKIs and ADCs, offering opportunities for rational next-line strategies.

Read About Lung Cancer Remission Rate on OncoDaily 

Conclusion

Amivantamab has emerged as one of the most important therapeutic innovations in EGFR-driven NSCLC. Its dual EGFR/MET inhibition mechanism addresses key resistance pathways, and clinical results across multiple Phase I–III studies consistently demonstrate meaningful, durable responses—even in historically refractory subgroups. With ongoing expansion into earlier lines of therapy and combinations with next-generation TKIs, amivantamab is reshaping the treatment landscape and may soon become foundational in EGFR-mutant lung cancer care.

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Written by Armen Gevorgyan, MD

Paul McCartney has joined calls for the EU to reject efforts to ban the use of terms such as “sausage” and “burger” for vegetarian foods.

The former Beatle has joined eight British MPs who have written to the European Commission arguing that a ban approved in October by the European parliament would address a nonexistent problem while slowing progress on climate goals.

The new rules would spell the end the use of terms such as steak, burger, sausage or escalope when referring to products made of vegetables or plant-based proteins. Suggested alternatives include the less appetising “discs” or “tubes”.

McCartney said: “To stipulate that burgers and sausages are ‘plant-based’, ‘vegetarian’ or ‘vegan’ should be enough for sensible people to understand what they are eating. This also encourages attitudes which are essential to our health and that of the planet.”

The musician is one of the world’s most prominent advocates of a vegetarian diet. He and his late wife founded the Linda McCartney plant-based foods brand in 1991 and he and their daughters Mary and Stella launched the global “Meat Free Monday” campaign to encourage people to eat less meat.

Linda McCartney sausages and burgers have been part of a global trend of increased interest in products to replace meat, even if investment has waned since a bubble during the coronavirus pandemic.

Yet with the growth of plant-based products has come a backlash, particularly from the politically powerful farming and meat distribution industries, which are worried about the potential effects of lower demand on jobs.

The European parliament voted 355–247 to ban “meat-related” names from being used on plant-based products. According to Euronews, Céline Imart, a French member of the centre-right European People’s Party and proponent of the ban, told the parliament: “I accept that steak, cutlet or sausage are products from our livestock farms. Full stop. No laboratory substitutes, no plant-based products.”

The letter signed by the McCartney family and the British MPs argued that the EU rules could force Britain into changes as well, because the markets and regulation are still so intertwined despite the UK’s departure from the EU.

The EU has a longstanding “geographical indication” system of preventing businesses from trading off the names of products associated with specific places, such as champagne (north-east France), Kalamata olives (southern Greece) or Parma ham (northern Italy). But the attempt to limit the use of generic terms is more controversial.

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Many of the terms that would be banned have malleable meanings. For instance, the Collins dictionary defines a sausage firstly in relation to meat but secondly as “an object shaped like a sausage”. Even more problematically for a ban, the primary definition of “burger” is given as a “flat round mass of minced meat or vegetables”.

The eight MP signatories to the letter include the former Labour leader Jeremy Corbyn and the former Green party co-leaders Carla Denyer and Adrian Ramsay.