Viking Therapeutics has been a key player in the development of novel therapeutics for metabolic and endocrine disorders, with their investigational drug VK2809 standing out as a significant advancement in the treatment of Nonalcoholic Steatohepatitis (NASH). This paper provides an overview of VK2809, detailing its clinical development, regulatory milestones, and the implications of its success in recent studies.

**Introduction to VK2809**

VK2809 is a liver-selective thyroid hormone receptor beta (THR-β) agonist developed by Viking Therapeutics. It targets liver tissue to reduce hepatic fat content and improve liver health markers in patients with NASH. By modulating lipid metabolism pathways selectively, VK2809 aims to offer significant therapeutic benefits in NASH without the systemic side effects associated with thyroid hormone therapy.

**Clinical Development and Trials**

The VOYAGE study, a Phase 2b clinical trial, was initiated by Viking Therapeutics in November 2019 to assess the efficacy, safety, and tolerability of VK2809 in patients with biopsy-confirmed NASH and fibrosis. This randomized, double-blind, placebo-controlled, multicenter international trial is designed to provide critical data on VK2809's potential as a therapeutic option for NASH patients [1].

**Regulatory Milestones**

A critical milestone for VK2809 was reached with the completion of enrollment in the Phase 2b VOYAGE study. This achievement underscores Viking Therapeutics' commitment to advancing the clinical development of VK2809 and highlights the significant interest within the medical community in exploring novel treatments for NASH, a condition that currently has limited therapeutic options [2].

**Recent Data and Implications**

At The Liver Meeting® 2023, new data from the Phase 2b VOYAGE study were presented, showcasing VK2809's potential in treating patients with biopsy-confirmed NASH. While specific results were not detailed here, the presentation of new data at such a prestigious conference indicates positive progress in VK2809's clinical development journey and its potential impact on NASH treatment paradigms [3].

**Preclinical Success**

In addition to its clinical trials, VK2809 has demonstrated potent reductions in plasma and liver lipids, as well as improvements in liver fibrosis in a rodent model of diet-induced NASH. VK2809-treated rodents also showed improvement in genes associated with lipid metabolism and suppression of genes associated with fibrogenic signaling, further supporting its potential efficacy in treating NASH [4].

**References**

1. Viking Therapeutics. (2019). "Viking Therapeutics Initiates VOYAGE Study for VK2809." [Online]. Available: https://vikingtherapeutics.com/pipeline/metabolic-disease-program/vk2809/
2. Viking Therapeutics. (2023). "Viking Therapeutics Announces Completion of Enrollment in Phase 2b VOYAGE Study of VK2809 in Patients with Biopsy-Confirmed Non-Alcoholic Steatohepatitis (NASH)." [Online]. Available: http://ir.vikingtherapeutics.com/2023-01-09-Viking-Therapeutics-Announces-Completion-of-Enrollment-in-Phase-2b-VOYAGE-Study-of-VK2809-in-Patients-with-Biopsy-Confirmed-Non-Alcoholic-Steatohepatitis-NASH
3. Viking Therapeutics. (2023). "Viking Therapeutics Presents New Data from Phase 2b VOYAGE Study of VK2809 in Patients with Biopsy-Confirmed Non-Alcoholic Steatohepatitis (NASH) at The Liver Meeting® 2023." [Online]. Available: http://ir.vikingtherapeutics.com/2023-11-13-Viking-Therapeutics-Presents-New-Data-from-Phase-2b-VOYAGE-Study-of-VK2809-in-Patients-with-Biopsy-Confirmed-Non-Alcoholic-Steatohepatitis-NASH-at-The-Liver-Meeting-R-2023
4. Viking Therapeutics. "Metabolic Disease Programs - Preclinical Data on VK2809." [Online]. Available: https://vikingtherapeutics.com/pipeline/metabolic-disease-program/

This compilation of references details the journey of VK2809 from its inception through clinical trials to recent presentations of data, highlighting its potential as a novel therapeutic option for NASH.

NGM Bio

The development of aldafermin by NGM Biopharmaceuticals, Inc. (NGM Bio) represents a significant advancement in the therapeutic landscape for Nonalcoholic Steatohepatitis (NASH), showcasing a novel approach to addressing this complex liver disease. Below are detailed references supporting the clinical progress, regulatory milestones, and broader implications of aldafermin's development journey.

**Introduction to Aldafermin**

Aldafermin, an engineered analog of the fibroblast growth factor 19 (FGF19), targets the core metabolic dysregulation in NASH. By mimicking FGF19, aldafermin aims to improve liver health, reduce liver fat content, and ameliorate fibrosis in patients with NASH. The unique mechanism of action of aldafermin positions it as a potentially transformative treatment option for NASH.

**Clinical Development and Trials**

NGM Bio's commitment to advancing aldafermin has been highlighted by its progression through clinical trials. The Phase 2b ALPINE 4 trial demonstrated significant improvements in liver fibrosis without worsening NASH, showcasing aldafermin's potential efficacy in treating this disease. These results are critical as they highlight aldafermin's ability to address one of the key treatment goals for NASH—improvement in liver fibrosis [4].

**Regulatory Milestones**

While specific details on regulatory milestones were not provided, the successful outcomes from Phase 2b trials and the initiation of further studies indicate a promising path toward regulatory review and approval. The positive data from these trials underscore NGM Bio's strategic efforts in advancing aldafermin through the development pipeline, aiming for eventual regulatory success.

**Expanding Clinical Applications**

Beyond its primary focus on NASH, aldafermin has been explored for other indications, including Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) and Bile Acid Malabsorption (BAM). An investigator-sponsored trial presented at Digestive Disease Week 2023 highlighted aldafermin's potential in treating these conditions, further showcasing NGM Bio's strategy to explore the broader therapeutic potential of aldafermin beyond liver diseases [1].

**Conclusion**

The development of aldafermin by NGM Bio represents an innovative approach to treating NASH, with promising clinical trial results and potential applications in other diseases. As NGM Bio continues to explore aldafermin's therapeutic potential, the drug stands as a beacon of hope for patients with NASH and other related conditions.

For more detailed information on aldafermin and its clinical development, please refer to the following sources:

1. NGM Bio Announces Presentation of Data from Phase 2 Investigator-Sponsored Trial of Aldafermin [https://ir.ngmbio.com/news-releases/news-release-details/ngm-bio-announces-presentation-data-phase-2-investigator] [1].
2. NGM Bio outlines evolved strategy for aldafermin focusing on rare conditions with significant unmet need [https://www.morningstar.com/news/globe-newswire/9014820/ngm-bio-announces-new-clinical-data-from-ongoing-trial-of-ngm707-in-advanced-solid-tumors-and-outlines-evolved-strategy-for-aldafermin-and-ngm120-to-focus-on-rare-conditions-with-significant-unmet-need] [2].
3. Safety and tolerability profile of Aldafermin consistent with prior trials [https://finance.yahoo.com/news/ngm-bio-announces-presentation-data-200500960.html] [3].
4. NGM Bio Announces Oral Plenary Presentation of Data from Phase 2b ALPINE 4 Trial [https://www.globenewswire.com/news-release/2023/10/11/2758807/35057/en/NGM-Bio-Announces-Oral-Plenary-Presentation-of-Data-from-Phase-2b-ALPINE-4-Trial-of-Aldafermin-in-Compensated-Cirrhosis-F4-Due-to-NASH-at-Upcoming-AASLD-The-Liver-Meeting.html] [4].

These references provide a comprehensive overview of aldafermin's development journey, illustrating its potential impact on the treatment landscape for NASH and beyond.

Akero FGF21 drug development for NASH/MASH

The development and potential of the drug efruxifermin (EFX), previously referred to as AKR-001, for the treatment of liver diseases, particularly Nonalcoholic Steatohepatitis (NASH), is a significant advancement in the field of hepatology. Efruxifermin, developed by Akero Therapeutics, is engineered to mimic the biological activity of the endogenous hormone FGF21 (Fibroblast Growth Factor 21), which plays a crucial role in regulating metabolism and energy balance. This drug represents a novel therapeutic approach by targeting the underlying metabolic dysfunctions associated with NASH.

**Background on NASH and FGF21**

NASH is a severe form of nonalcoholic fatty liver disease (NAFLD) characterized by liver inflammation and damage due to fat buildup in the liver. It can progress to more severe conditions such as cirrhosis and liver cancer. The role of FGF21 in metabolism, including its effects on glucose and lipid metabolism, makes it an attractive target for NASH treatment. FGF21 regulates multiple metabolic pathways and has beneficial effects on body weight, insulin sensitivity, and lipid profiles.

Fibroblast Growth Factor 21 (FGF21) is a pivotal hormone in the regulation of metabolism and energy homeostasis, making it a prime target for therapeutic interventions in metabolic diseases such as Nonalcoholic Steatohepatitis (NASH). FGF21 is primarily produced in the liver, but also in adipose tissue and the pancreas, and it acts on various tissues throughout the body to exert its metabolic effects. The multifaceted role of FGF21 includes the regulation of carbohydrate and lipid metabolism, energy expenditure, and insulin sensitivity, which are all crucial aspects in the pathophysiology of NASH.

FGF21 exerts its effects through binding to a complex receptor system consisting of β-Klotho and FGFR1c (Fibroblast Growth Factor Receptor 1c). This interaction triggers a cascade of intracellular signaling pathways that lead to the modulation of glucose and lipid metabolism. Specifically, FGF21 has been shown to:

- Enhance insulin sensitivity and glucose uptake in adipocytes, contributing to improved glycemic control.
- Stimulate lipolysis in adipose tissue, leading to reduced lipid accumulation and amelioration of lipotoxicity, which is a critical factor in the development of NASH.
- Increase energy expenditure through promoting thermogenesis in brown adipose tissue.
- Suppress lipogenesis in the liver, thereby reducing hepatic fat accumulation.

These actions collectively contribute to the potential of FGF21 as a therapeutic target for conditions characterized by insulin resistance and metabolic dysfunction, such as NASH.

FGF21 represents a promising target for metabolic disease therapy, with its wide-ranging effects on metabolism offering a potentially comprehensive approach to treating conditions like NASH. However, ongoing research and clinical trials are crucial to fully understand its therapeutic potential and optimize treatment strategies.

**Efruxifermin (EFX) Development**

Efruxifermin has been designed to confer the therapeutic benefits of native FGF21 with improved pharmacokinetics. The engineered version of FGF21 in EFX has a half-life of three to four days, which supports once-weekly dosing, making it a convenient option for patients [1]. Akero Therapeutics has positioned EFX as its lead drug candidate for the treatment of NASH, highlighting its potential to address the multifaceted nature of the disease by improving liver health, insulin sensitivity, lipid profiles, and reducing body weight [2].

**Clinical Trials and Results**

Despite the promising mechanism of action and preclinical studies, the path to proving efruxifermin's efficacy in humans has encountered challenges. In a Phase 2b study, efruxifermin missed its primary endpoint of showing significant improvement in liver fibrosis without worsening of NASH. The mixed results from this trial led to a significant drop in Akero Therapeutics' share value, underscoring the complexities and challenges in developing effective therapies for NASH [3].

**Conclusion**

Efruxifermin represents a novel approach to treating NASH by targeting the metabolic dysfunctions at the heart of the disease. While early results have shown promise, the journey towards full approval and validation of its efficacy underscores the challenges inherent in drug development for complex diseases like NASH. Continued research and clinical trials will be crucial in determining efruxifermin's place in the treatment landscape for liver diseases.

For further information on efruxifermin and its development, visit Akero Therapeutics' official website and relevant scientific publications on NASH and FGF21-based therapies.

**References:**

1. "Akero picks up $65M to advance Amgen-licensed NASH drug." FierceBiotech. [Link](https://www.fiercebiotech.com/akero-picks-up-65m-to-advance-amgen-licensed-nash-drug)
2. "Akero Therapeutics | EFX for NASH | Fc-FGF21 Fusion Protein." AkeroTX. [Link](https://akerotx.com/efruxifermin/)
3. "Akero drug for NASH misses goal in mid-stage study." BioPharma Dive. [Link](https://www.biopharmadive.com/news/akero-nash-symmetry-trial-results-fibrosis-liver/696109/)

The development of lanifibranor by Inventiva is a significant stride in the fight against Nonalcoholic Steatohepatitis (NASH), a complex liver disease. This paper expands on the references cited to provide a deeper understanding of lanifibranor's journey through clinical trials, its financial backing, and strategic developments aimed at bringing this promising drug to market.

**Clinical Development and Trials**

Inventiva's announcement regarding the clinical development of lanifibranor included plans for a new Phase III trial targeting patients with NASH and compensated cirrhosis, underscoring the drug's progression into later stages of clinical testing. This decision was made public on January 4, 2023, highlighting Inventiva's commitment to advancing lanifibranor's development based on promising earlier phase results [1].

The pivotal Phase III clinical trial, known as NATiV3, aims to evaluate the long-term efficacy and safety of lanifibranor in adults with NASH. The trial's initiation involved the activation of the first clinical sites and the start of patient screening, marking a significant milestone in lanifibranor's journey towards regulatory approval [2].

**Financial Strategy and Support**

To support its clinical endeavors, Inventiva secured financial backing through a significant transaction with the European Investment Bank. On January 10, 2024, Inventiva drew down the second tranche of €25 million under the existing Finance Contract with the bank. This funding is earmarked to support parts of the pivotal NATiV3 Phase III clinical trial evaluating lanifibranor in patients with NASH. This financial move demonstrates both the confidence in lanifibranor's potential and Inventiva's strategic planning in ensuring the drug's continued development [3].

**Expanding Clinical Trials and Global Reach**

The Phase 3 study evaluating the efficacy and safety of lanifibranor in adults with NASH and liver fibrosis stages F2 or F3 is structured into two sequential parts: an initial double-blind placebo-controlled period (Part A) followed by a double-blind active treatment extension period (Part B). This design aims to thoroughly assess lanifibranor's impact over an extended period, providing comprehensive data on its efficacy and safety profile [4].

**Conclusion**

The development of lanifibranor by Inventiva represents a beacon of hope for patients suffering from NASH. Through strategic clinical trials, substantial financial backing, and a clear vision for global reach, Inventiva is poised to make significant contributions to the treatment landscape of this challenging liver disease. The continued progress of lanifibranor through clinical development and towards regulatory approval will be closely watched by the medical community and patients alike, eager for new therapeutic options in the fight against NASH.

**References:**

1. [Inventiva announces changes to the clinical development of lanifibranor, including plans for a new Phase III trial in patients with NASH and compensated cirrhosis](https://inventivapharma.com/inventiva-announces-changes-to-the-clinical-development-of-lanifibranor-including-plans-for-a-new-phase-iii-trial-in-patients-with-nash-and-compensated-cirrhosis/) [1].
2. [Inventiva announces the initiation of its pivotal Phase III clinical trial evaluating lanifibranor in NASH](https://www.globenewswire.com/news-release/2021/09/08/2293792/0/en/Inventiva-announces-the-initiation-of-its-pivotal-Phase-III-clinical-trial-evaluating-lanifibranor-in-NASH.html) [2].
3. [Inventiva draws down the second tranche of €25 million under existing Finance Contract with the European Investment Bank](https://www.globenewswire.com/news-release/2024/01/10/2807470/0/en/Inventiva-draws-down-the-second-tranche-of-25-million-under-existing-Finance-Contract-with-the-European-Investment-Bank.html) [3].
4. [A Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension Period in Adult Subjects With NASH](https://classic.clinicaltrials.gov/ct2/show/NCT04849728) [4].

Hepatic Encephalopathy (HE) -- A stranger lives inside me.

I've talked with many who have experienced the condition but this was my first time. It was very different from what I imagined.  This blog is particularly aimed at care givers and family members who find themselves interacting with someone that they don't recognize.

It is not an uncommon course with this disease in its advanced stages for the patient to become angry, short tempered, and even mean. We see reports from people who no longer recognize their loved one.  The warm, gentle, loving person they have known has somehow become a vengeful tyrant. This makes the job of caring for the needs of that patient very difficult. I can't help much to lighten the burden but perhaps a bit of understanding can make it easier to accept.

Chapter 2: Defining Your Why

Posted by Sarah Larsen · August 29, 2023 4:30 PM

Are You In Control Of Your Health?

Posted by Sarah Larsen · August 14, 2023 3:06 PM

We Need to Talk

Posted by Sarah Larsen · July 31, 2023 1:12 AM

If you would like to watch some very good videos about liver disease,

click here to take a video tour

Fatty Liver & Liver Cirrhosis Are At Epidemic Levels!

• 100,000,000 Americans have a fatty liver.  Most don't know it.
• 20,000,000 will develop liver fibrosis disease or NAFLD (nonalcoholic fatty liver disease) as a result.
• 5,000,000 million will progress to liver cirrhosis or NASH (nonalcoholic steatohepatitis) and possibly end stage liver failure.  
• Some will be lucky enough to be listed for a transplant, the only cure for late stage liver disease, but 30% of those listed will die waiting.  Death by liver failure is long and difficult.  
• We want to help you avoid this kind of death by helping you understand how you may be killing yourself slowly.  And, what you can do about it.
• If you are already ill, we will do our best to help you with that process.

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Our Mission

To improve the diagnosis, treatment & support of Americans with fatty liver, NAFLD or NASH through awareness, education, screening and patient advocacy.

Click here to learn more.

We Advocate Early Screening

Typically, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are silent diseases.  They have no symptoms. Even if cirrhosis has developed, there are often no symptoms until the liver has become so damaged that the only option is a liver transplant.

There is currently a quick, easy and economical method to screen for fatty liver disease called a FibroScan.  Unfortunately, the current medical standards policy is not to screen for liver disease.  And, unless you are sick and have symptoms, insurance probably won't pay for the scan, even if you're lucky enough to have a testing system in your area.

The Fatty Liver Foundation is championing a nationwide program to provide liver screening services to make it possible for people who have a concern for their liver health to get an inexpensive scan.  Since insurance doesn't normally cover screening for people who aren't sick yet, it will be on a private pay basis.  However, as a nonprofit foundation, we believe we can deliver this service at an affordable price.

Click here to learn more.

If you would like to watch some very good videos about liver disease,

click here to take a video tour