Metabolic disorders are conditions that disrupt normal metabolism and the process of converting food to energy at the cellular level. They affect the ability of the cell to perform critical biochemical reactions that involve the processing or transport of proteins (amino acids), carbohydrates (sugars and starches), or lipids (fatty acids). Metabolic disorders can take many forms, with obesity and diabetes being the most common.

The worldwide prevalence of obesity has nearly tripled between 1975 and 2022. Once considered a high-income country problem, obesity is  on the rise even in low- and middle-income countries.

In Issue 5 of The Altascientist, we investigate the challenges of metabolic disorders, with insights from Altasciences’ clinical and preclinical experts, as well as:

• Frequently asked questions about clinical trials for metabolic disorders
• An Altasciences case study
• A hidden threat: nonalcoholic fatty liver disease (NAFLD)
• Altasciences’ end-to-end patient recruitment process and patient access for NASH studies

Obesity, Diabetes, and Metabolic Dysfunction

As obesity continues to rise globally, the risk of developing associated metabolic disorders, including type 2 diabetes, has escalated.

Several epidemiologic studies reveal a direct link between the escalation of obesity and diabetes. The pathophysiology connecting the two metabolic disorders is mainly attributed to two factors: insulin resistance and insulin deficiency. Research shows that if you are obese, your chances of developing type 2 diabetes are 80 times greater than a person whose body mass index (BMI) is within a normal range (under 25).

Type 2 diabetes is a dysfunction in the way the body metabolizes glucose, causing it to rely on alternative energy sources from tissues, muscles, and organs. Individuals suffering from the disease are either resistant to insulin or do not produce enough of it to maintain healthy blood glucose levels.

Nonalcoholic Fatty Liver Disease (NAFLD)

Much like obesity and diabetes, nonalcoholic fatty liver disease (NAFLD) is a global epidemic, with prevalence rates reaching 25% to 30%. NAFLD can be divided into the milder form, nonalcoholic fatty liver (NAFL), and the more aggressive form, nonalcoholic steatohepatitis (NASH).  It is characterized by different levels of hepatic steatosis (fat deposition), inflammation (in NASH), and fibrosis.

Despite the growing prevalence of NAFLD/NASH, treatment options remain extremely limited. A large number of pharmaceutical companies have started to conduct clinical studies to develop treatments for NASH, but recruiting patients for these types of studies is particularly challenging as this disease does not present with clear symptoms, and the majority of patients do not know they have it or are not diagnosed until significant damage to the liver has occurred.

“One of our ultimate goals is to develop approaches for better diagnosis and management of chronic liver disease, which is currently an increasing worldwide concern, and demands early-phase trials that require specific imaging and biomarker services. We are continuously expanding Altasciences’ therapeutic offerings in gastrointestinal disease-specific studies, particularly those intended to investigate the efficacy of drugs in patients with NASH.”

Dr. Gaetano Morelli, MD, Executive Vice President Medical Affairs,
Chief Medical Officer

Altasciences saw the developing need for patients with NASH and proactively built a database of patients suffering from the disease using an IRB-approved protocol we sponsored ourselves. Since NASH patients are often underdiagnosed, Dr. Gaetano Morelli used his expertise in NASH to build a campaign based on a set of criteria the patients will recognize as applicable to them. 

Altasciences’ Expertise in Metabolic Disorders

Our ability to effectively recruit patients, our clinical operational experience, and our robust list of validated bioanalytical assays—including exenatide, glucagon, insulin glargine, M1, M2, insulin aspart, and metformin—provide the perfect solution for organizations studying obesity and developing treatments for metabolic disorders.

“We have conducted many different types of studies in these patient populations, from first-in-human (FIH), single ascending dose (SAD) to proof-of-concept (POC) studies. The focus of the studies ranges from glucose tolerance to pharmacokinetics, comparing obese subjects to those with normal weights.”

Ingrid Holmes, Vice President, Global Clinical Operations

Explore all issues of The Altascientist in our Resource Center. And don’t forget to subscribe to “The Altascientist: Audiobooks” on Spotify, Apple Podcasts, or wherever you get your audio content. 
 

Biologics have become the fastest-growing class of therapeutic compounds, with seven of the top-10 selling drugs in 2023 being biologics, each exceeding sales of $10 billion USD.  In 2022, biosimilars accounted for 13.7% of all spending on biologics, compared with the 8.9% in 2021.

Biologics have provided treatment options for people who suffer from some of the most serious medical conditions, such as cancer and genetic disorders.

A biosimilar is a copy of a biologic medicine that is similar, but not identical, to the original medicine. It enters the market subsequent to the patent expiration of a previously authorized version of a biologic. A biosimilar is approved only after showing that it is “highly similar” to an approved biological product, known as the reference product, in terms of structure, purity, potency, safety, pharmacokinetics, and in many cases, efficacy, with allowable minor differences.

In Issue 4 of The Altascientist, learn about the growing interest of biosimilars, and key considerations in pharmacokinetic (PK) studies, as well as:

• The rise of the biosimilar market
• The regulatory landscape
• How Altasciences puts biosimilars to the test
• Altasciences’ expertise in bioanalysis  
• Key considerations for biosimilar clinical pharmacology studies
• Ensuring the continued success of biosimilar programs

Considerations and Study Challenges for Biosimilars

Early awareness of study challenges is crucial in running a successful early-phase biosimilar development program, and certain considerations must be taken into account before beginning a study.

Recruitment is often one the most challenging aspects of the biosimilar clinical trial process and can lead to trial delays if not managed effectively. The inclusion and exclusion criteria for healthy participants in a biosimilar bioequivalence study are often much stricter than a standard bioequivalence study on a small molecule.

Additionally, as a biosimilar product is not exactly the same as the reference product, there are also increased safety risks associated with the administration of the test product. Key safety considerations include immunogenicity, hypersensitivity reactions, and an increased risk for other adverse effects.

How Altasciences  Can Support Your Biosimilar Drug Development

Bioanalytical considerations are another important factor. Unlike small molecule drugs, biologics exhibit a significant level of complexity which is driven by the fact that their production is dependent on a living system, such as a microorganism, a plant, or animal cells.

Altasciences supports method development, GCP/GLP-compliant biosimilar assay development validation, and sample analysis for PK and immunogenicity/anti-drug antibody (ADA) testing, and we are proud of our bioanalytical expertise with LC-MS/MS and ligand binding platforms . We provide support for all stages of drug development (discovery to preclinical to Phase IV) for both small and large molecules programs.

“Altasciences has the perfect mix of innovator and generic drug development experience, with a thorough understanding of the regulatory complexities involved in biosimilar clinical pharmacology studies. Companies developing biosimilars are collaborating with us because of our firsthand experience, distinctive recruitment strategies, and speed in conducting biosimilar clinical trials that require a customized approach based on the therapeutic indication and study-specific goals. Our expertise allows us to accelerate our clients’ biosimilar development programs so they can offer greater treatment options and more cost-effective medications to patients in need.”–Danielle Salha Senior Director, Global Immunology, Ligand Binding Assays

Explore all issues of The Altascientist in our Resource Center. And don’t forget to subscribe to “The Altascientist: Audiobooks” on Spotify, Apple Podcasts, or wherever you get your audio content. 
 

^{Originally published June 2018 / Updated April 2022}

Prescription drugs, including opioid analgesics, are an important component of modern pain management; however, along with their euphoric effects comes an increased possibility of misuse and abuse—all of which can lead to addiction, overdose, or death.

The FDA has undertaken many efforts to help clinicians
manage this widespread issue by instating guidelines
to better understand the abuse potential of new
drugs, and ensure drugs currently on the market are less likely to be abused through the use of abuse-deterrent formulations (ADFs). The FDA guidance, Assessment of Abuse Potential of Drugs, states that a broad range of CNS drugs require human abuse potential (HAP) studies, also known as human abuse liability (HAL) studies, to evaluate the abuse liability of drugs in development, and to determine the relative risk of abuse before a drug comes to market.

In Issue 3 of The Altascientist, we look at the intricacies and key considerations involved in conducting these sensitive HAP studies, including: 

• FDA’s steps to limit the misuse and abuse of prescription drugs
• human abuse potential study solutions
• study design and protocol
• a case study

Human Abuse Potential Study Designs

HAP studies are clinical pharmacology studies and play a key role in the overall abuse potential assessment of a new chemical entity (NCE). As per the FDA’s guidance, Altasciences’ HAP studies are conducted with participants who have experience with recreational drug use in the same pharmaceutical class as the NCE, or with drugs with similar psychoactive properties.

Psychedelics are gaining interest for treating psychiatric illnesses. Altasciences’ experts can guide a clinical development strategy to evaluate safety, pharmacokinetics, and pharmacodynamics. With a team recognized in pharmacology, addiction, and regulatory services, we can help build your target product profile and clinical development plan, ensuring comprehensive studies and data early to support regulatory milestones and FDA meetings.

Abuse potential evaluation is also required to evaluate novel formulations designed to specifically reduce or deter abuse of a drug. According to the National Center for Drug Abuse Statistics, 16 million, or 6% of Americans over the age of 12, abuse prescription drugs every year. In addition, many individuals misuse their prescription medications by tampering with the formulation. The FDA has worked to address this problem by encouraging the development of abuse-deterrent formulations (ADFs) for opioids and other drugs that are associated with a high risk of abuse. 

These products are formulated with properties expected to meaningfully deter certain types of abuse and/or make abuse more difficult or less rewarding. This allows patients who are in chronic pain to have appropriate access to drugs, such as opioid analgesics, with significantly less risk of abuse through unintended routes, such as intranasal insufflation or injection.

Explore all issues of The Altascientist in our Resource Center. And don’t forget to subscribe to “The Altascientist: Audiobooks” on Spotify, Apple Podcasts, or wherever you get your audio content.