The impact of FDA-approved pancreatic enzyme replacements cannot be overstated. In fact, the World Health Organization (WHO) includes pancreatic enzymes on the 'Model List of Essential Medicines' for both adults and children. These 'living' lists are assessed and updated every two years to identify the 'minimum medicine needs for a basic health care system, listing the most efficacious, safe and cost effective medicines for priority conditions.' For many, especially those with cystic fibrosis or living without a pancreas, replacement enzymes are lifesaving and life-sustaining.
Research into next-generation replacement enzymes seeks to improve upon current challenges for those who use PERTs in whatever capacity - from supportive care, such as in mild to moderate pancreatic insufficiency, to life-long dependency. Amongst the concerns of those either making (R&D sector) or taking (patients) replacement enzymes are:
- Dosing consistency/individualized dosing - there is no one size fits all method for prescribing enzymes (especially when there are three types of enzyme in each pill!), most individuals on pancreatic enzymes benefit most from the lipase
- Enzyme source - due to personal or religious reasons, enzymes derived from pigs is not an available dietary addition
- Side effects - bloating, gas, stomach pain, diarrhea, constipation and nausea are all listed as side effects for replacement enzymes at normal dosing regimes; although rare, long-standing enzyme overdose can lead to a condition called fibrosing colonopathy
- Additional required medication - it is very common to co-prescribe a proton pump inhibitor alongside replacement enzymes to regulate gastric pH (and these come with their own list of side effects!)
Anthera Pharmaceuticals is a small biotech company in California focusing on a next-generation pancreatic enzyme replacement therapy which aims to reduce patient pill burden. The most common ways for PERTs to fail is patient non-compliance, fundamentally forgetting to take enzymes prior to every meal and snack. This often means taking up to 6 pills 4-5 times per day, every day, to ensure therapeutic benefit. One way to reduce the quantity of daily pills is to improve the quality of the enzymes in each pill. The proprietary enzyme blend in Anthera's Sollpura drug candidate is biologically engineered (this means made from a biological organism such as a bacteria - no pigs involved!) and features crystalline and cross-linked enzymes. Crystallization and cross-linking bring stability to the enzyme molecules, ensuring that low gastric pH and the presence/absence of bile salts do no effect their availability. In addition, Sollpura has been formulated into both a tablet and sachet (water-soluble!) form, the later being particularly attractive for pediatric cystic fibrosis patients with pancreatic insufficiency. The Sollpura formulations are currently in two clinical trials.
AzurRx BioPharma is a publically traded biopharmaceutical company working in the areas of gastrointestinal and microbiome-related disorders and diseases. Their drug candidate, MS1819 lipase is currently in phase IIa clinical trials (to profile the safety and efficacy in comparison with currently available PERTs). As the name suggests, this produce is either a lipase-only enzyme capsule or one which features a significant percentage of lipase with respect to amylase and protease. As described on their website, although amylases and proteases are produced alongside lipases in the pancreas, only supplementation of the lipase is thought to be necessary for treatment of EPI. In fact, proteases in currently approved PERTs have been implicated in the cause of fibrosing colonopathy, a rare but very serious side effect of taking replacement enzymes. Looking to the microscopic world for answers, MS1819 lipase has also been biologically engineered - but this time from yeast rather than bacteria! Yes, the same microorganisms which serve us by fermenting wheat to make bread, grapes to make wine and hops to make beer have been engineered to produce highly potent and stable lipases for treating EPI.
Anthera and AzurRx are just two of a growing number of biopharmaceutical companies approaching pancreatic enzyme improvements using non-traditional (biological) methods. The use of microorganisms such as bacteria, yeast and algae for the production of valuable materials including antibiotics (many of which are also on the WHO's Model List of Essential Medicines), food and even crude oil demonstrates the viability and influence of biologically-derived products. A biological approach to enzyme production may provide not only a renewable and reliable method for enzyme production (with the potential to tailor enzymes on an individual basis) but may help alleviate the burden we place on animal-derived healthcare products.
AzurRx BioPharma is a publically traded biopharmaceutical company working in the areas of gastrointestinal and microbiome-related disorders and diseases. Their drug candidate, MS1819 lipase is currently in phase IIa clinical trials (to profile the safety and efficacy in comparison with currently available PERTs). As the name suggests, this produce is either a lipase-only enzyme capsule or one which features a significant percentage of lipase with respect to amylase and protease. As described on their website, although amylases and proteases are produced alongside lipases in the pancreas, only supplementation of the lipase is thought to be necessary for treatment of EPI. In fact, proteases in currently approved PERTs have been implicated in the cause of fibrosing colonopathy, a rare but very serious side effect of taking replacement enzymes. Looking to the microscopic world for answers, MS1819 lipase has also been biologically engineered - but this time from yeast rather than bacteria! Yes, the same microorganisms which serve us by fermenting wheat to make bread, grapes to make wine and hops to make beer have been engineered to produce highly potent and stable lipases for treating EPI.
Anthera and AzurRx are just two of a growing number of biopharmaceutical companies approaching pancreatic enzyme improvements using non-traditional (biological) methods. The use of microorganisms such as bacteria, yeast and algae for the production of valuable materials including antibiotics (many of which are also on the WHO's Model List of Essential Medicines), food and even crude oil demonstrates the viability and influence of biologically-derived products. A biological approach to enzyme production may provide not only a renewable and reliable method for enzyme production (with the potential to tailor enzymes on an individual basis) but may help alleviate the burden we place on animal-derived healthcare products.
No comments:
Post a Comment