Latest Pharmaceutical Studies On SARMs

sarms studies

In the last few years, there has been a significant surge in the acceptance of nonsteroidal Selective androgen receptor modulators (SARMs) as a promising alternative for testosterone replacement therapies.

A novel class of androgen receptor ligands, SARMs can be classified as synthetic drugs designed to have effects similar to those of Testosterone. They are believed to have the same kinds of effects as anabolic steroids but SARMs are much more selective in their action and this is exactly what differentiates them from steroids and other drugs. Some of the biggest advantages that help SARMs outscore over current therapies include androgen receptor specificity, tissue selectivity, oral bioavailability, flexibility of structural modification, and the lack of steroid-related side effects.

Here are excerpts from some pharmaceutical studies on SARMs that would be beneficial to understand their action mechanism and benefits.

  1. In a study conducted on one hundred twenty female Sprague-Dawley rats aged to twenty-three weeks, the rats were assigned to 12 treatment groups. Treatment with drugs was initiated on an immediate basis following ovariectomy and it continued for a period of 120 days. Dual energy x-ray absorptiometry measured body composition, whole body bone mineral density, and lumbar vertebrae BMD.
S4 (Andarine) chemical structure

S4 (Andarine) chemical structure

The study found that treatment with S4 (Andarine) was beneficial to maintain cortical content, and whole body and trabecular BMD. The S4 treatment also decreased body fat and increased body strength in these animals. It was further disclosed by this study that S4 had the ability to reduce the incidence of fracture via minimizing the incidence of falls through increased muscle strength and through direct effects in bone as compared to current therapies that are primarily antiresorptive in nature. The study also found that dosages of S4 were effective to increase lean mass and reduce body fat in intact and ovariectomized rats. It was also revealed that S4 provides the unique potential to prevent bone resorption, increase skeletal muscle mass/strength positions, and promote bone anabolism that makes it a possible new alternative for the treatment of osteoporosis.

Furthermore, the S4 treatment also had a positive effect on cortical bone and bone strength. In addition to this, S4 dose also proved effective to increase the differentiation of bone marrow cells towards the osteoblast lineage. This study also highlighted that S4 treatment resulted in a caused a significantly larger increase in total body bone mineral density than Dihydrotestosterone (DHT). Furthermore, the drug also significantly decreased plasma luteinizing hormone and follicle-stimulating hormone levels in castrated animals in a dose-dependent manner and demonstrated agonist activity in the pituitary.

  1. A different study revealed the clinical efficacy data for LGD-4033, MK-3984, MK-0773, and Enobosarm (GTx-024, Ostarine, and S-22) for the prevention and treatment of muscle wasting associated with cancer. A nonsteroidal SARM, Enobosarm was found to stimulate better physical function and increases in lean body mass across several populations along with a lower hazard ratio for survival in cancer patients. Results for the Phase III clinical trials entitled Prevention and treatment of muscle wasting in Patients with Cancer1 (POWER1) and POWER2 evaluating Enobosarm for the prevention and treatment of muscle wasting in patients with non-small cell lung cancer will likely establish Enobosarm as the first drug for the prevention and treatment of muscle wasting in cancer patients.
  2. A study on Selective Androgen Receptor Modulators (SARMs) as Function Promoting Therapies disclosed that a number of nonsteroidal SARMs act as full agonists in muscle and bone and as partial agonists in prostate. This study reiterated the benefits of SARMs to improve bone health and physical function without affecting the prostate and cardiovascular outcomes.

The study highlighted that SARMs are extremely useful clinically to treat a wide range of health complications, including cancer cachexia, osteoporosis, aging and chronic disease, and frailty. This study also revealed that Selective Androgen Receptor Modulators have the ability to positively influence life of living beings that is prone to fractures, mobility limitation, physical disability, risk of falls, and poor quality of life.

LGD-4033 chemical structure

LGD-4033 chemical structure

  1. In another study, LGD-4033 (an oral selective androgen receptor modulator) was found to bind androgen receptor with high affinity and selectivity. During this study, 76 healthy men (21–50 years) were randomized to placebo or 0.1, 0.3, or 1.0 mg LGD-4033 daily for a period of 21 days as part of the placebo-controlled study. The researchers measured prostate-specific antigen, electrocardiogram, hormones, blood counts, chemistries, lipids, lean and fat mass, and muscle strength during and for 5 weeks after intervention.

It was found by the study that LGD-4033 (Anabolicum) was well tolerated. No drug-related serious adverse events were noticed during the study. This study disclosed that there was a long elimination half-life in the context of LGD. Furthermore, administration of LGD was associated with dose-dependent suppression of sex hormone–binding globulin, high density lipoprotein cholesterol, total testosterone, and triglyceride levels. The study also revealed that LGD had favorable pharmacokinetic profile, was safe, and increased lean body mass even during the short period without resulting in a change in prostate-specific antigen. The study also emphasized that LGD-4033 had the potential to increase periosteal bone formation, bone mineral density, and femur bending strength in preclinical models.

In short, it can be said that Selective androgen receptor modulators have been highly effective to treat health implicate and improve quality of life in more than just a way.

PAT: Driving the Future Of Pharmaceutical Quality

pharmaceutical manufacturing

The concept of Process analytical technology (PAT) has revolutionized and redefined the mechanism in the segment of pharmaceutical manufacturing.

The pharmaceutical manufacturing industry that had to work within the rigid constraints of regulation for many years has welcomed this initiative by the U.S. Food and Drug Administration for current good manufacturing practices (CGMPs). This has been primarily because PAT has made things easier and simplified for the pharmaceutical manufacturing industry to adopt new technologies for improving manufacturing.fda cgmps

Introduction

Process analytical technology can be defined as an extensive system to design, analyze, and control pharmaceutical manufacturing via timely quality measurements along with performance attributes of materials and processes.

PAT is a real-time testing and adjustment process that includes physical, chemical, mathematical, and microbiological risk analysis that is executed in appropriate manner. The fundamental principle of this approach includes quality cannot be tested but it can be instead built by design into the medicinal product.

pat explained

Till recently, the pharmaceutical manufacturing industry was reluctant to embrace PAT for many reasons. The primary reason was that PAT application will further add to current regulatory requirements. Secondly, this new technology will bring out more questions related to suitability, validation, and chemometrics of the method. Thirdly, many experts believe that regulatory uncertainty/risk results in “Don’t Tell” or “Don’t Use” practice.

PAT was not widely accepted initially by the pharmaceutical manufacturing sector as significant process and formulation changes would have been required during technology transfer and scale up. To add to that, several “bridging” studies such as accelerated stability testing and human bioavailability would have been almost necessitated for ensuring unchanged safety and efficacy profile.

Advantages Of PAT

PAT offers many advantages, including but not limited to:

  • Providing high quality drugs to the general public in a timely manner;
  • Optimal utilization of private and public resources to meet growing healthcare requirements;
  • Reaping advantages of a variety of new drug development opportunities that would be created by advancements in the segments of Biology and Chemistry

Process analytical technology proves its real mettle for Blending purposes. It offers the potential to reduce cycle time and scrap. In addition to these advantages, PAT could be useful to facilitate improved and efficient control of raw materials. Moreover, PAT is beneficial to reduce the likelihood of “segregation” post blending step and also facilitates adequacy of mix in the context of all critical components.

Fostering a culture of continuous process improvements, this approach has the prowess of acknowledging a critical reality: manufacturers of life sciences’ products cannot rely on fixed process control schemes for creating repeatable results. Manufacturers are bound to face variability issues in product quality because of variability in equipment, raw materials, and processing conditions and these variabilities are unavoidable. Therefore, the need to have a robust strategy for developing processes with control and measurement capabilities like PAT were required that have the ability to compensate for process variability.

benefits of Process Analytical Technology

The pharmaceutical manufacturing industry can easily reap benefits of this technology and achieve a high degree of repeatability and efficiency in processes and sub-processed via active management of the processes to make the concept of Quality Assurance a real-time and continuous activity. In short, PAT is the word to reduce over-processing, minimize rejects, and improve consistency to bring a broader change in pharmaceutical manufacturing.