Digital Transformation in Pharma Manufacturing

Patent Cliff Deals, Tariff Pressures, and the In Vivo Cell Therapy Bet

Behind the Headlines, Episode 23

ICH Q12 and Post-Approval Changes

Speed, Flexibility Top Large-Molecule Manufacturing Trends

Drug Digest July 2025

Key Insights from Industry Survey Results

Bio/Pharma's Tariff Response

Feliza Mirasol is the science editor for 

Dan Williams, CEO of SynaptixBio emphasizes how small biotechs are using genetic research and partnerships to accelerate rare disease innovation in the final installment of his interview.

The Role of Genetic Advances and Partnerships in Rare Disease Drug Development (Part 3)

Because small biotechnology companies can leverage their agility and focus to drive innovation—where larger pharmaceutical firms may hesitate—small biotechs are playing a pivotal role in advancing treatments for rare diseases, says Dan Williams, PhD, CEO of SynaptixBio, in the third installment of his interview with 

According to Williams, whose company specializes in ultra-rare diseases, “small biotechs ... are able to move things forward ... [and] make decisions extremely quickly,” allowing them to respond rapidly to new data and research opportunities. A significant factor in rare disease research is the genetic basis of these conditions. “About 80% of rare diseases are genetic,” Williams notes, highlighting the impact of recent advances in genome sequencing on diagnostics and drug development.

How are genetic research and strategic partnerships propelling rare disease drugs?

Over the past decade, collaborations with academic institutions, such as the Children’s Hospital of Philadelphia, have deepened understanding of genetic components, accelerating the path from discovery to clinical trials, Williams explains. Despite their strengths, small biotechs face funding challenges. While grant opportunities are increasing in both the United States and United Kingdom, securing resources remains a major hurdle, Williams points out.

As rare disease treatments progress through clinical development, partnerships with larger pharmaceutical companies become essential. These collaborations bring the rigorous methodologies and resources needed to bring new therapies to market, says Williams. In addition, patient advocacy groups are also shaping the landscape, providing critical input on treatment priorities and quality of life improvements. As research momentum builds, the integration of genetic insights, agile biotech strategies, and collaborative partnerships is set to transform the future of rare disease therapeutics, he concludes.

Click the video above to view this interview.

Dan Williams, PhD, studied biochemistry and physiology at the University of Dundee, after which he worked his way up to senior scientist—managing a cell research group and preclinical development. Following this, he moved to drug development, focusing on the organization and management of both manufacturing and clinical trials. Williams then moved to Adaptimmune, developing cell therapies. He set up the development groups, project managing preclinical research and clinical trials, before becoming vice-president of Research Operations. From there, he moved to Meatable as chief product officer. Williams co-founded SynaptixBio in 2021.

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Japan-based Nxera Pharma (Nxera) and Cancer Research UK announced on Sept. 17, 2025 that the first dosing of patients in a Phase IIa clinical trial (NCT05944237) has begun. The trial is meant to evaluate HTL0039732 (also known as NXE0039732), Nxera’s investigational small-molecule immunotherapy drug, in treating advanced solid tumors (1).

HTL0039732 is designed to block signaling through the prostaglandin E2 (PGE2)-type prostanoid receptor 4 (EP4). According to Nxera in a company press release, PGE2 acts in the tumor microenvironment to trigger cancer cells to evade the immune system (1). Unlike many existing immunotherapies, which rely on targeting immune checkpoints, EP4 antagonism addresses tumor-mediated immunosuppression within the microenvironment. This approach is of particular interest for drug developers seeking new strategies against cancers that historically respond poorly to current immunotherapies.

“The initiation of the Phase IIa trial marks a significant step forward in our efforts to bring this promising drug to patients with difficult-to-treat cancers,” said Matt Barnes, PhD, chief scientific officer and president of Nxera Pharma UK, in the press release (1). “The encouraging data from the Phase I study provide a strong foundation for continued clinical investigation, and we look forward to sharing further updates as the trial progresses.”

The ongoing trial, which is sponsored and managed by Cancer Research UK’s Center for Drug Development, is being led by Bristi Basu, PhD, of the University of Cambridge and Debashis Sarker, PhD, of King’s College London. The lead clinical site is Addenbrooke’s Hospital, Cambridge, UK, with additional enrollment at Experimental Cancer Medicine Center network locations.

The Phase IIa expansion will examine four tumor cohorts: microsatellite stable colorectal cancer, gastric or gastroesophageal junction adenocarcinoma, clear cell renal cell carcinoma, and metastatic castration-resistant prostate cancer. These tumor types represent areas of high unmet need, particularly in the context of immunotherapy resistance (2–5).

In an earlier Phase I study, patients with advanced, treatment-resistant solid tumors received HTL0039732 in combination with the checkpoint inhibitor atezolizumab. Results from this study included two confirmed partial responses in distinct tumor types, along with evidence of selective EP4 engagement without significant EP2 activity. These findings suggest that EP4 inhibition could complement existing immunotherapy modalities, potentially extending their reach into tumor types less responsive to current standards, according to Nxera.

“It is exciting to move to the next phase of assessing this new inhibitor of an important receptor EP4, which is implicated in suppression of the antitumor immune response,” said Basu in the release. “We hope that by combining it with immunotherapy, we will build on some of the promising early data we have seen in patients treated in the Phase I trial.”

What implications does the clinical development of HTL0039732 have on the broader oncology landscape?

From a drug development perspective, HTL0039732 exemplifies the trend toward small-molecule immuno-oncology approaches, offering oral administration and potential synergy with biologic checkpoint inhibitors. For drug manufacturers, the combination of small-molecule scalability with immunotherapy integration highlights the importance of flexible production strategies capable of supporting diverse treatment modalities.

“The dosing of the first patient in the Phase IIa trial of HTL0039732 is a significant step forward in the Center for Drug Development’s collaboration with Nxera Pharma, which exemplifies the power of partnership in accelerating the development of groundbreaking therapies,” said Lars Erwig, PhD, director of Cancer Research UK’s Center for Drug Development, in the release. “The need for novel immunotherapies is more pressing than ever, as many cancers continue to evade current treatments. We look forward to continuing this journey and bringing hope to patients and their families.”

As interest grows in targeting non-traditional immune pathways, the Phase IIa trial will be closely watched by those working in cancer drug research and manufacturing. Its outcomes could influence future strategies for integrating small molecules into immunotherapy pipelines and expanding therapeutic options for resistant solid tumors.

Nxera Pharma and Cancer Research UK Announce First Patient Dosed in Phase 2a Trial of Investigational Cancer Immunotherapy HTL0039732

. Press Release. Sept. 17, 2025.
2. Gandini, A.; Puglisi, S.; Pirrone, C.; et al. The Role of Immunotherapy in Microsatellites Stable Metastatic Colorectal Cancer: State of the Art and Future Perspectives. 


3. Chung, D. T.; Tung, D. S.; Dung, T. N. Harnessing Immune Checkpoint Inhibitors Against Gastric Cancer: Charting the Course to Expanded Therapeutic Benefit. 


4. Braun, D. A.; Bakouny, Z.; Hirsch, L.; et al. Beyond Conventional Immune-Checkpoint Inhibition—Novel Immunotherapies for Renal Cell Carcinoma. 


5. Bansal, D.; Reimers, M. A.; Knoche, E. M.; Pachynski, R. K. Immunotherapy and Immunotherapy Combinations in Metastatic Castration-Resistant Prostate Cancer. 

Articles

Japan-based Nxera Pharma and Cancer Research UK have initiated a Phase IIa clinical trial to evaluate HTL0039732, a small-molecule immunotherapy targeting the EP4 receptor, in advanced solid tumors. This trial, managed by Cancer Research UK, focuses on tumor types with high unmet needs, such as microsatellite stable colorectal cancer and metastatic castration-resistant prostate cancer. The drug's mechanism, which blocks PGE2 signaling, aims to overcome tumor-mediated immunosuppression. The trial's outcomes could influence future strategies for integrating small molecules into immunotherapy pipelines.

The Phase IIa study will test HTL0039732 in combination with immunotherapy to boost responses in resistant solid tumors and broaden treatment choices.

Cancer Research UK Partners with Nxera on Next-Stage Trial for HTL0039732 

Patrick Lavery is an Editor for the MJH Life Sciences brands 

. Previously at MJH, he filled the same role for 

Silica gel granules | Image Credit: © Coprid - stock.adobe.com

Sanner, a provider of customized solutions for medical devices, diagnostics, pharmaceuticals, and consumer healthcare based in Germany, is lining up the equipment and expertise the company plans to display at CPHI Frankfurt, which will be held Oct. 28–30, 2025 (1–3).

In a press release, Sanner said that in the last two years, it has significantly expanded its contract development and manufacturing organization (CDMO) services, particularly in the areas of complex drug delivery and medical device solutions, establishing new manufacturing sites and acquiring two industry-leading design centers of excellence (1).

Who is Sanner’s new CEO, and what’s his background?

“Sanner occupies an important market position in healthcare packaging globally,” Sanner Group CEO Stefan Verheyden, who will attend CPHI as the first trade show in his new role, said in the press release (1). “With our expanded capabilities and a clear vision, we are ready to solidify a leading position in the MedTech CDMO space.”

Verheyden was announced as the next CEO of Sanner in August 2025 (4). In his previous capacity as global vice-president, Sales, Pharma & Biopharma Solutions—Injectables at Gerresheimer, Verheyden 

 as part of its Pharmapack Europe coverage in January 2025 about packaging trends for the year ahead.

At that time, Verheyden saw movement toward more at-home therapies and personalized medicine, saying autoinjectors and other drug delivery devices would need to be prioritized to accommodate this trend (5). View the full interview 

What else will Sanner showcase at the conference?

Aside from offering its experts’ knowledge in the finer points of CDMO partnerships, Sanner said it will present its pharmaceutical packaging portfolio at CPHI Frankfurt, including an improved packaging solution for oral solid dosage products that was design-optimized with tailored dessicant solutions, identifying the most proper dessicants even for active ingredients that are highly sensitive (1).

According to Sanner, this approach helps to ensure faster product launches through predictive stability modeling and achievement of stability targets.

“Together with our talented teams and strategic partners, we are committed to shaping the future of our packaging and MedTech business,” Verheyden said (1). “We will continue to invest in advanced technologies, global infrastructure, and customer-centric innovation to deliver exceptional value to our clients and stakeholders.”

How are preparations going for CPHI Europe 2025?

 more than 63,000 professionals from the bio/pharmaceutical industry as the conference celebrates its 36th year; CPHI Milan drew more than 59,000 attendees in the fall of 2024 (2,3).

For 2025, the three-day event will feature six content theatres and more than 2000 exhibitors, including expanded zones that event organizer Informa Markets said reflect recent diversification in the industry: bioproduction, finished dosage formulation, drug delivery, and packaging, in addition to a traditional focus on APIs (2,3).

®’s continuing coverage of CPHI Europe in 2025. Sanner will be located at Booth 0J92, in Hall 8 (1).

Sanner at CPHI: Combining CDMO Excellence and Moisture Management Expertise.

 Press Release. Sept. 17, 2025.
2. Lavery, P. 

CPHI Frankfurt Expected to Draw More Than 60,000 Attendees in October.

, Sept. 12, 2025.
3. Informa Markets. CPHI Frankfurt 2025 to Welcome More Than 60,000 Pharma Professionals as the Global Event Returns to Germany. Press Release. Sept. 5, 2025.
4. Sanner. 

Sanner Strengthens Its Position as CDMO—Important Management Change.

 Press Release. Aug. 8, 2025.
5. Haigney, S. 

Pharmapack Europe 2025: Packaging Trends.

Sanner, a German provider of medical device and pharmaceutical solutions, is set to showcase its expanded capabilities at CPHI Frankfurt 2025. The company has significantly enhanced its CDMO services, focusing on complex drug delivery and medical device solutions, and has established new manufacturing sites. Stefan Verheyden, the new CEO, aims to solidify Sanner's position in the MedTech CDMO space. At the conference, Sanner will present its pharmaceutical packaging portfolio, including optimized solutions for oral solid dosage products, emphasizing faster product launches and stability targets.

The company has expanded its CDMO offerings in recent years, adding to decades of experiences in solutions such as moisture management.

Sanner Previews CPHI Frankfurt Portfolio of CDMO Services, Packaging Innovations

Ozempic, Mounjaro and Wegovy injectable pens on white background | Image Credit: © K KStock - stock.adobe.com

 (Lilly) on Sept. 9, 2025 has been made public, regarding a direct-to-consumer program that originally aired in the United States on the ABC television network on March 18, 2024, and has been available ever since on ABC’s website and the streaming service Hulu (1,2). FDA said it “determined that the video is false or misleading” in its evaluation of two tirzepatide injections, marketed by Lilly as Mounjaro and Zepbound (1).

Who was interviewed for the program? What was Lilly’s contribution?

The TV special, entitled “Shame, Blame, and the Weight Loss Revolution,” was hosted by Oprah Winfrey and, according to FDA’s warning letter, featured 

, MD, director of Obesity Medicine at the Cleveland Clinic, and 

, MD, director of Obesity Medicine at Cedars-Sinai Medical Center in Los Angeles, as paid consultants who “receive research funding from companies making GLP-1 [glucagon-like peptide-1] drugs” (1,2).

The Winfrey program also interviewed Rhonda Pacheco, PharmD, who at the time was a group vice-president for Lilly (1). On Sept. 11, 2025, Pacheco was announced as the new president of Takeda Pharmaceuticals’ United States Business Unit (3).

What is FDA alleging has been misrepresented?

FDA determined that the program “creates a misleading impression regarding the safety of Zepbound and Mounjaro” and “omits important risk information and otherwise minimizes the risks of these drug products” (1).

The agency cited failure to adequately disclose a boxed warning for thyroid C-cell tumors, as well as minimization of adverse events such as pancreatitis and hypoglycemia. It also noted that Lilly had not submitted the promotional material for review at the time of dissemination, as required (1).

As Reuters reported, the FDA warning letter to Lilly was just one among dozens issued on Sept. 9, including another concerning the same ABC program that was sent to 

, Novo Nordisk’s senior vice-president of Cardiometabolic Sales, was also featured in the video, which discussed the company’s semaglutide injections, Ozempic and Wegovy, and the liraglutide injection Victoza (4).

 also received a warning about its compounded semaglutide products, the active ingredient in Ozempic and Wegovy, after FDA found false or misleading claims about those products in a review of the Hims website in August 2025 (5).

The Reuters report cited comments made by FDA Commissioner Marty Makary, MD, during the week that the letters were issued, suggesting that companies needed to present a balanced view of the drugs they promote, while complying with advertising rules—including listing all side effects (5). Makary said FDA intended to distribute approximately 100 cease-and-desist notices, among thousands of other letters.

What does this signal for compliance culture?

The recent cluster of warning letters indicates that advertising, media appearances, and digital platforms are under renewed scrutiny. For companies in competitive therapeutic areas such as metabolic disease, governance frameworks must extend to consultants, third-party platforms, and direct-to-consumer websites.

The agency’s coordinated action suggests that enforcement will no longer be episodic but ongoing, shaped by both scientific evidence and public communication practices.

, last updated Sept. 16, 2025 (accessed Sept. 16, 2025).
2. ABC. 

Watch An Oprah Special: Shame, Blame and The Weight Loss Revolution.

, March 18, 2024 (accessed Sept. 16, 2025).
3. Takeda. 

Takeda Appoints Rhonda Pacheco President of the US Business Unit.

, last updated Sept. 16, 2025 (accessed Sept. 16, 2025).
5. Roy, M.; Choudhury, K. 

US FDA Sends Drug Advertising Warning Letters to Lilly, Novo, Hims.

The FDA issued a warning letter to Eli Lilly regarding a misleading direct-to-consumer program about tirzepatide injections, Mounjaro and Zepbound. The program, hosted by Oprah Winfrey, featured experts with ties to GLP-1 drug companies and omitted critical risk information, including a boxed warning for thyroid C-cell tumors. The FDA also sent similar warnings to Novo Nordisk and Hims & Hers Health for misleading claims. This indicates increased scrutiny on advertising and compliance, emphasizing the need for balanced drug promotion and adherence to advertising regulations.

Misleading promotions of GLP-1 and compounded semaglutide products are drawing renewed regulatory scrutiny over risk disclosure and safety messaging.

Lilly, Novo, Hims Get FDA Warnings About Misleading Drug Communications

Close up shot pharmacist holding nasal spray medicine at the drugstore.Seasonal health issues | Image Credit: © I Viewfinder - stock.adobe.com

 (Corstasis) has announced FDA’s approval of its bumetanide nasal spray, Enbumyst, for the treatment of edema associated with congestive heart failure (CHF) and both hepatic and renal disease, including nephrotic syndrome in adults (1).

With approximately 6.7 million Americans living with heart failure, and associated fluid overload causing more than 1 million hospitalizations every year, accounting for billions of dollars in United States healthcare expenditures, Corstasis said the nasal spray addresses a critical unmet need; together, fluid overload and edema are the leading causes of hospitalization—and readmission—for patients with CHF, cirrhosis, and chronic kidney disease (1).

A nasal spray treatment for edema in these patients, Corstasis said, may help bridge the gap between oral loop and intravenous (IV) diuretics. The former can be limited by delayed onset and poor gastrointestinal absorption, while the latter requires administration in a hospital or infusion setting, using resources and increasing healthcare expenditures (1). Conversely, Enbumyst has been designed as an outpatient, self-administered therapy.

In clinical studies, according to Corstasis, the nasal spray demonstrated rapid absorption and predictable diuretic response, showing comparable effects on diuresis, natriuresis, and urinary potassium excretion in comparison to IV bumetanide injection (1).

A press release from Corstasis Therapeutics encapsulated the reactions of numerous industry professionals with knowledge of the nasal spray’s potential.

“Enbumyst offers the potential to change the standard of care by enabling earlier, outpatient intervention,” said 

, MD, director of Heart Failure Research at the Mount Sinai Fuster Heart Hospital in New York, in the press release (1). “This innovation may meaningfully improve outcomes while potentially easing the economic burden on the healthcare system.”

“Enbumyst was designed in direct collaboration with cardiologists to address practical challenges in the outpatient care setting,” said 

, MD, chief medical director of Corstasis, director of the Non-Invasive Vascular Lab at the Orange County Heart Institute, and director of Structural Heart Disease at Providence St. Joseph Hospital in Orange, Calif. (1).

“The FDA approval of Enbumyst represents a meaningful advancement in the treatment of edema for patients and providers,” said 

, chief executive officer of Corstasis Therapeutics (1).

Are other effective nasal sprays emerging on the market?

Another nasal spray, ARS Pharmaceuticals’ epinephrine nasal spray Neffy (commercialized outside the US, Australia, New Zealand, Japan, and China by ALK as EURneffy), had a first large-scale analysis demonstrating real-world, clinical evidence of treatment outcomes 

accepted for publication as correspondence

, ARS Pharma announced on Sept. 8, 2025 (2,3). The nasal spray’s performance was observed in routine clinical practice in patients experiencing anaphylaxis symptoms during oral food challenge and allergen immunotherapy.

Learn more about the findings in that analysis, and the other top 

® stories from the week of Sept. 8, in the “PharmTech Weekly Roundup” accessible at 

Corstasis said it expects to launch Embumyst in the US in the fourth quarter of 2025, and will target cardiologists, nephrologists, hepatologists, outpatient heart failure clinics, and integrated delivery networks (1).

Corstasis Therapeutics Announces FDA Approval of Enbumyst (bumetanide nasal spray) for the Treatment of Edema Associated with Congestive Heart Failure, Liver Disease and Kidney Disease.

 Press Release. Sept. 15, 2025.
2. ARS Pharmaceuticals. 

Real-World Evidence Supports Clinical Effectiveness of Neffy (epinephrine nasal spray) in Patients Experiencing Anaphylaxis.

 Press Release. Sept. 8, 2025.
3. Lavery, P. 

Epinephrine Nasal Spray Comparable to Injection in Real-World Data of Patients Experiencing Anaphylaxis.

Corstasis Therapeutics has received FDA approval for Enbumyst, a bumetanide nasal spray, to treat edema linked to congestive heart failure, hepatic, and renal diseases. This nasal spray addresses the limitations of oral and IV diuretics by offering rapid absorption and predictable diuretic response, suitable for outpatient use. Experts highlight its potential to transform care standards and reduce healthcare costs. Corstasis plans to launch Enbumyst in the US by late 2025, targeting cardiologists, nephrologists, hepatologists, and outpatient heart failure clinics.

Corstasis Therapeutics plans to launch the product in the United States in the fourth quarter of 2025.

FDA Approves Cortasis Nasal Spray, Enbumyst, for Edema

Cheryl Barton is director of PharmaVision, 

Digital composite of highlighted red painful liver of woman | Image credit: ©

Metabolic dysfunction-associated steatohepatitis (MASH) is a type of non-alcoholic fatty liver disease (NAFLD) affecting more than 250 million people worldwide, and the number of cases in advanced stages is expected to double by 2030. Underlying conditions such as obesity, type 3 diabetes, and metabolic syndrome can increase the risk of MASH. For many years, MASH has been difficult to treat, and several products have failed in clinical development, including Genfit’s peroxisome proliferator-activated receptor (PPAR) agonist elafibranor, Gilead's ASK1 inhibitor selonsertib, Intercept Pharmaceuticals' farnesoid X receptor (FXR) agonist obeticholic acid, and Novartis/Conatus' pan-caspase inhibitor emricasan.

In the past few years, significant progress has been made, and new products have entered the MASH market. In March 2024, the US Food and Drug Administration (FDA) approved Madrigal Pharmaceuticals’ orally active, selective thyroid hormone receptor (THR)-β agonist, Rezdiffra (resmetirom), for adults with MASH with moderate to advanced liver scarring (fibrosis), alongside diet and exercise (1). In June 2025, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) recommended granting conditional marketing authorization for Rezdiffra in MASH (2). On 19 Aug. 2026, the European Commission approved Rezidiffra, and the company is planning its first European launch in Germany in the fourth quarter of 2025 (4).

In August 2025, Novo Nordisk received FDA approval for its injectable weight-loss drug Wegovy (semaglutide) for patients with MASH and moderate to advanced liver fibrosis, without cirrhosis, in combination with a reduced-calorie diet and exercise (4). The conditional clearance was based on Phase III results, where the glucagon-like peptide-1 receptor agonist (GLP-1RA) demonstrated improved liver scarring without worsening the condition and resolved MASH without making scarring worse (5,6). Eli Lilly is also seeking approval for its injectable dual-action gastric inhibitory polypeptide (GIP)/GLP-1RA, Zepbound (tirzepatide), based on its Phase II SYNERGY-MASH trial in patients with and without type 2 diabetes, and with stage 2 or 3 fibrosis (scarring) (7,8).

What investments are Big Pharma making in MASH?

MASH is seen as the next frontier in metabolic diseases, and numerous clinical trials are underway evaluating hormone analogs, receptor agonists, and enzyme inhibitors 

MASH drug development has attracted significant interest from pharma and private investors. In the GLP-1 space, Boehringer Ingelheim has teamed up with UK-based Zealand Pharma to develop survodutide. This dual glucagon/GLP-1 agonist has demonstrated a placebo-adjusted 64.8% improvement in fatty liver disease (9).

Table I. Clinical development of therapies targeting Metabolic dysfunction-associated steatohepatitis (MASH).

Table I. Clinical development of therapies targeting Metabolic dysfunction-associated steatohepatitis (MASH) (Continued).

In May 2025, GSK acquired Boston Pharmaceuticals' lead asset efimosfermin for US$1.2 billion plus US$800 million in milestone payments. Efimosfermin is a novel, once-monthly fibroblast growth factor 21 (FGF21) analog therapeutic in Phase II clinical development for the treatment of MASH (10). US-based Akero Therapeutics and 89bio are also developing FGF21 analogs, efruxifermin and pegozafermin, respectively (11, 12).

Which European frontrunners are targeting MASH?

Several European biotechs are developing innovative approaches to target the underlying cause of MASH and liver fibrosis. These include:

focuses on developing novel small-molecule therapies targeting fibrosis, lysosomal storage disorders, and oncology. Its lead program, lanifibranor (IVA337), is an orally active pan-PPAR agonist. It demonstrated promising results in a Phase IIb placebo-controlled trial in patients with active MASH, improving the resolution of MASH without worsening fibrosis (13). Lanifibranor is currently being evaluated in NATiV3, a pivotal Phase III clinical trial in patients with MASH and fibrosis stages F2 and F3; the trial is due to complete in September 2026 (14).

 is a clinical-stage biopharmaceutical company specializing in fibrolytic and anti-inflammatory diseases. Its lead compound, Vonafexor, is an orally active, non-steroidal agonist of NR1H4 (FXR, or bile acid receptor). In the Phase II LIVIFY study, Vonafexor significantly reduced liver fibrosis and inflammation markers, decreased liver fat and weight, and improved liver and kidney functions (15). In January 2024, the company raised €39 million (US$45.39 million) in Series C funding to develop Vonafexor further (16).

, is a biotechnology company focused on discovering and developing innovative peptide-based medicines. It has created several candidates targeting the metabolic brain axis, including Survodutide, a glucagon/GLP-1 dual agonist, which is being developed with Boehringer Ingelheim for MASH (Phase II) and obesity (Phase II), and petrelintide, an amylin analogue that it is co-developing with Roche. This compound could represent a new class of treatment for obesity (17).

In the United States, several biotech companies are working on MASH candidates, including MetaVia, which is developing DA-1726, a novel oxyntomodulin (OXM) analogue that functions as a glucagon-like peptide-1 receptor (GLP1R) and glucagon receptor (GCGR) dual agonist (18).

Additionally, significant progress has been made in developing biomarkers and diagnostics to identify patients at risk of MASH. For example, France-based Genfit has created a non-invasive diagnostic program that includes an 

test to detect NIS4+ and NIS2+. At the same time, Nordic Bioscience has identified biomarkers targeting neo-epitopes of collagen fragments that can be used to risk-stratify patients. (19, 20).

The global MASH market was valued at US$7.9 billion in 2024 and is forecast to grow to US$31.8 billion by 2033, with a compound annual growth rate of 17.7% from 2025 to 2033 (21). After many failed attempts, the industry has finally identified new ways to reduce liver fat buildup. While Madrigal's orally active Rezdiffra was the first to enter the US and European Union markets, it now faces competition from Novo’s injectable Wegovy, and Eli Lilly is not far behind. It will be interesting to see how the MASH landscape evolves and whether new approaches, such as oxyntomodulin analogues and gene silencing agents, can capture a share of this lucrative market in the future.

FDA Approves First Treatment for Patients with Liver Scarring Due to Fatty Liver Disease

Madrigal Receives European Commission Approval for Rezdiffra™ (resmetirom) for the Treatment of MASH with Moderate to Advanced Liver Fibrosis.

Madrigal Pharmaceuticals Reports Second-Quarter 2025 Financial Results and Provides Corporate Updates.

FDA Approves Treatment for Serious Liver Disease Known as ‘MASH’

Sanyal, A. J.; Newsome, P. N.; Kliers, I.; et al.

 Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis

Semaglutide 2.4 mg Demonstrates Superior Improvement in Both Liver Fibrosis and MASH Resolution in the ESSENCE Trial.

Loomba, R.; Hartman, M. L.; Lawitz, E. J.; et al. (2024). T

irzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis

Survodutide US FDA Breakthrough Therapy Phase 3 Trials MASH.

GSK. GSK to Acquire Efimosfermin, a Phase III-Ready Potential Best-in-Class Specialty Medicine to Treat and Prevent Progression of Steatotic Liver Disease (SLD). Press Release. 14 May 2025.

 akerotx.com/clinical-trials (accessed 20 Aug. 2025).

89bio Receives EMA PRIME Status for Pegozafermin in the Treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH) with Fibrosis and Compensated Cirrhosis.

Francque, S. M.; Bedossa, P.; Ratziu, V.; et al.. 

A Randomized, Controlled Trial of the Pan-PPAR Agonist Lanifibranor in NASH. 

ClinicalTrials.gov. Study Details | A Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With (NASH) and Fibrosis Stages F2 and F3 ( NATiV3 ) (accessed 21 August 2025).

Ratziu, V.; Harrison, S. A.; Loustaud-Ratti; et al. 

Hepatic and Renal Improvements with FXR Agonist Vonafexor in Individuals with Suspected Fibrotic NASH. 

ENYO Pharma. ENYO Pharma Announces a €39 Million Series C Financing and FDA Clearance to Advance Vonafexor in a Phase 2 Clinical Trial for Patients with Alport syndrome. Press Release. 3 Jan. 2024.

MetaVia Doses First Patient in the 48 mg MAD Cohort of Its Phase 1 Clinical Trial Evaluating DA-1726 for the Treatment of Obesity to Further Explore Maximum Tolerated Dose.

Nash Or Mash Treatment Market Growth Rate, Industry Insights and Forecast 2025-2033

Cheryl Barton, PhD, is founder and director of PharmaVision, Pharmavision.co.uk.

Metabolic dysfunction-associated steatohepatitis (MASH), a subtype of non-alcoholic fatty liver disease, is projected to see a significant increase in advanced cases by 2030. Recent advancements include FDA and EMA approvals of Madrigal Pharmaceuticals' Rezdiffra and Novo Nordisk's Wegovy for MASH treatment. Big Pharma is heavily investing in MASH, with companies like GSK acquiring assets and others developing innovative therapies. European biotechs are also making strides with novel treatments. The MASH market is expected to grow substantially, driven by new therapeutic approaches and diagnostic advancements.

Novo Nordisk’s Wegovy will be competing with Madrigal Pharmaceuticals’ Rezdiffra in the metabolic dysfunction-associated steatohepatitis arena. 

Competition in MASH is Heating Up as GLP-1s Gate-Crash the Party

Ana Ali, R&D Tax Consultant, RCK Partners

The views and opinions expressed herein are those of the author and do not necessarily reflect the views or positions of

.

Behind every pharmaceutical breakthrough is a company that made a strategic investment into high-risk R&D, without guaranteed success. For the United Kingdom’s small- and medium-sized pharmaceutical firms, taking that step has become increasingly difficult. While the UK government has signalled strong support for life sciences through its 

 and a £520 million (~US$688 million) recommitment to the 

Life Sciences Innovative Manufacturing Fund

, financial tools must be equally fit for purpose if the UK wants to sustain its role as a global innovator.

A strong and vibrant small and medium enterprises (SME) ecosystem is essential to drive the innovation that fuels the pharmaceutical sector. Yet, the UK now trails behind such countries as Germany and Sweden in both gross domestic expenditure on R&D and business enterprise expenditure on R&D as a share of gross domestic product (1). Without adequate support for SMEs, this gap may widen—diminishing the UK’s appeal as a destination for R&D investment.

So, what changes must be implemented to drive the UK pharmaceutical industry to reach its full potential?

Understanding the complexities of R&D tax relief

At the heart of this discussion is the UK’s R&D tax relief framework. For years, the system has enabled innovation, especially among SMEs with tight margins and ambitious R&D plans. Between 2022 and 2023, the scientific and technical sector made up 17% of all R&D tax relief claims (2). This relief has provided countless eligible businesses with valuable assistance, enabling them to accelerate growth and ultimately further their R&D efforts.

Crucially, R&D tax relief is not exclusively awarded on successful projects. This makes it particularly well suited to the pharmaceutical sector, where high failure rates are part of the innovation process. By ensuring that firms can still receive relief for unsuccessful trials and experiments, the system acknowledges the realities of drug discovery and development.

However, while there are considerable benefits for innovative firms who are claiming R&D tax relief, understanding the specific nuances of the eligibility criteria and navigating the tax regimes is critical.

For companies with accounting periods beginning on or after April 1, 2024, the 

 offer a streamlined process but also introduce a new layer of complexity, which may make it more difficult for companies unfamiliar with R&D tax relief to engage with the benefits.

Navigating these criteria, understanding qualifying expenditures, and calculating the new credit rates now demand a level of tax literacy that many smaller firms simply don’t have in-house.

However, the onus to adapt practices also falls on His Majesty's Revenue and Customs (HMRC). To combat bad actors, HMRC has substantially increased their compliance activity, clamping down on fraudulent and erroneous activity within the R&D tax relief scheme. As a result, HMRC’s mass compliance approach has inadvertently deterred genuine claimants with eligible projects who are put off by the potential for time-consuming checks.

Furthermore, to truly future-proof innovation within the sector, we need to delve deeper. Research presented at a 2024 event hosted by London Business School and sponsored and by RCK Partners suggests that to maintain the UK’s competitive edge in innovation, the government could revisit the tax relief system and introduce targeted incentives for R&D-intensive SMEs (1). What’s clear is that governmental interventions to streamline guidance and improve access to information could be key to empowering more businesses to take advantage of these incentives and to accelerating innovative projects.

Financial incentives don’t just bridge funding gaps—they influence strategic decisions. When SMEs know that support is available and accessible, they are more likely to take bold steps, explore novel approaches, and invest in long-term R&D. Without that assurance, innovation stalls, talent leaves, and the entire ecosystem suffers.

The UK has a golden opportunity to revitalize its pharmaceutical sector. But to seize it, we need incentives that reflect the realities of early-stage pharmaceutical research and development: high failure rates, long timelines, and particular recognition of the role of small firms in driving big breakthroughs.

R&D tax relief should be a beacon for innovation, not a maze. By improving access, tailoring incentives, and fostering trust between business and government, the UK can turn policy into progress and keep its life sciences sector at the forefront of global innovation.

Comparative Review of the UK's R&D Tax Relief Scheme Relative to Other OECD Countries

. London Business School, 2024. Accessed September 12, 2025.

Research and Development Tax Credits Statistics: September 2024 - GOV.UK

The UK pharmaceutical sector faces challenges in maintaining its global innovation leadership, particularly for small and medium-sized enterprises (SMEs). Despite government support through initiatives like the Life Sciences Sector Plan, financial tools such as R&D tax relief are crucial. The current tax relief framework supports innovation but requires complex navigation, especially with upcoming changes. HMRC's increased compliance measures may deter genuine claimants. To sustain innovation, the government should streamline guidance, improve access to information, and introduce targeted incentives for R&D-intensive SMEs, ensuring the sector's continued growth and competitiveness.

UK pharma small- and medium-sized enterprises face funding and R&D barriers. Improved tax relief and targeted incentives are vital to keep UK innovation competitive.

Op/Ed: Rethinking R&D Tax Relief–Why Smarter Incentives Are Key to Unlocking UK Pharma Innovation

Conceptual stop sign with stormy background. Warning, caution and danger sign | Image Credit: © Rechitan Sorin - stock.adobe.com

The pharmaceutical industry stands at a critical juncture, as a recent report suggests FDA is considering a significant departure from its long-standing practice of utilizing external expert advisory committees for new drug applications (1). This potential shift, initially signaled by George Tidmarsh, head of FDA’s Center for Drug Evaluation and Research, has profound implications for regulatory strategy, transparency, and internal quality systems, directly impacting the core concerns industry professionals.

Historically, FDA advisory committees, established in their current form in 1972, have served a crucial role by convening external experts to review evidence and vote on the approval of drugs, vaccines, and medical devices, particularly when the agency faces complex or difficult decisions (2). Tidmarsh, however, argues that these panels are redundant and time-consuming, involving "a tremendous amount of work for the company and for the FDA." He suggests that the agency should instead focus its efforts on "big questions," such as evaluating appropriate endpoints for different drug classes.

A key part of the FDA's rationale for this potential change is the recent initiative to publish Complete Response Letters (CRLs) in real time (3). These letters, which previously required Freedom of Information Act requests, provide developers with "early insight into regulatory deficiencies to improve development planning." Tidmarsh posits that releasing CRLs promotes a level of transparency "akin to the advisory meetings’," suggesting the letters make expert committee meetings on individual drugs redundant (1).

However, this perspective is met with considerable pushback from former FDA officials, academics, and industry experts. Critics argue that abandoning expert reviews would "shield the agency’s decisions from public scrutiny” (1). Robert Califf, former FDA Commissioner, finds Tidmarsh’s reasoning "hard to follow," emphasizing that it is "extremely useful for people inside FDA to find out what other experts think before they make their final decisions" and essential for public understanding (1).

How do CRLs and expert review committees differ?

Experts highlight several critical differences between CRLs and advisory committee meetings:

• Public Input and Dialogue: Advisory committees allow experts to ask questions of the company or FDA that might not have been considered, and provide a vital public forum for comment on FDA decisions (1). A disclosed CRL informs the public 

 an application was rejected, while an advisory meeting seeks 

 a decision is made, a crucial distinction.

The FDA is contemplating a shift away from using external expert advisory committees for new drug applications, a move that could significantly impact regulatory strategy, transparency, and internal quality systems. George Tidmarsh, head of the FDA’s Center for Drug Evaluation and Research, argues that these committees are redundant and time-consuming. Critics, however, warn that this could reduce public scrutiny and transparency. The potential change emphasizes the need for robust internal quality systems and proactive communication to maintain public trust and ensure compliance in the pharmaceutical industry.

This potential shift has profound implications for regulatory strategy, transparency, and internal quality systems, directly impacting the core concerns of industry professionals.

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