Alcresta Therapeutics
The Science Of Enzymes

Meet Tim, an eight-year-old boy living with cystic fibrosis (CF). Inside his regular school backpack lies a small bag containing his CF medication—pancreatic enzyme supplements, multivitamins, antibiotics, and anti-inflammatory agents, among other capsules. Since the enzymes must be consumed at least 40 minutes prior to every meal, Tim is required to time his medication cycles to precision. If not, he faces the short-term consequences of poorly-digested food and severe long-term ripple effects emanating from damaged lungs and pancreas.

Despite ample add-ons of nutrients, he has stopped growing in height, and his body mass index (BMI) isn’t trending in the right direction. In hopes of supporting nutritional gains, Tim’s doctor has added supplemental enteral tube feeding for an average of six hours every night. However, he isn’t making the expected weight and height gains and suffers from GI side effects of poorly digested fats from the enteral feeds like bloating, nausea and diarrhea, further exasperating his nutritional intake.

One of the root causes of Tim’s lack of nutritional gains and side effects is lack of a needed enzyme called lipase to breakdown fat during enteral feeding. As a result, he receives fewer calories, key fats (omega-3, omega-6), and lower levels of critical vitamins. Since the fat in enteral tube feeding formulas is in triglyceride form and Tim is not producing the enzyme needed, they don’t break into their absorbable forms (fatty acids and monoglycerides), causing Tim to suffer from perennial malabsorption.

Tim represents a large proportion of patients—suffering from CF, short bowel syndrome (SBS), or gastrointestinal (GI) symptoms—that rely upon enteral tube feeding for their nutrition. Unfortunately, much of the critical nutrients in their liquid formula are going to waste, a realization that drove Alexey Margolin, Ph.D., to spend countless hours in his laboratory to find a solution.

After years of research, Margolin discovered a method to break the fat in liquid formula down to its absorbable form and laid the cornerstone of Alcresta Therapeutics, in 2011. “He answered the critical question, ‘how can you break downcrucial nutrients from fats so enterally fed-children can get the right caloric intake to make height/weight/BIM gains?’ More importantly, he worked to help children with pancreatic insufficiency keep pace with population norms for their age groups,” says Daniel Orlando, the CEO of Alcresta, a company that develops enzyme-based products to address the challenges children/patients living with GI disorders and rare diseases face.

Today, Tim and others like him stand to benefit from RELiZORB, Alcresta’s first-of-its-kind digestive enzyme cartridge designed to mimic the function of pancreatic lipase (the breaking down of fats into an absorbable form). Built with Alcresta’s proprietary enzyme immobilization technology, RELiZORB can be easily attached to an enteral feeding tube (a matter of inserting and twisting!). The cartridge’s ingredient, lipase enzyme, is immobilized to tiny beads (iLipase) which are retained in the cartridge by two filters. As a result, when feeding tube formula passes through RELiZORB, it makes contact with iLipase, and the formula is duly broken down into fatty acids and monoglyceride.

Just like that, Tim’s nightly enteral diet receives a three-fold increase in essential nutrient factors, and he is considerably healthier and potentially able to stave off respiratory complications. For patients that suffer from CF, sustaining a high BMI is vital to avoid respiratory infections. In a chronic setting, this is potentially the biggest benefit of RELiZORB.

Over the two studies that spanned up to 90 days, we demonstrated that RELiZORB breaks down up to 90 percent of fats in enteral feeding formulas

The proof is in the pudding. Since its full commercial launch in January 2019, RELiZORB’s formulary has been adopted by over 200 hospitals across the country. Orlando cites two clinical studies in 2017 and 2018 that introduced RELiZORB to the medical community, “Over the two studies that spanned up to 90 days, we demonstrated that RELiZORB breaks down up to 90 percent of fats in enteral feeding formulas. Pediatric and adult patients saw an almost three-fold increase in the absorption of essential Omega-3 fatty acids after a single RELiZORB use.” During the two studies, RELiZORB not only improved the caloric intake of patients but also reduced the side effects associated with enteral feeding, such as diarrhea, nausea, and GI symptoms.

RELiZORB’s Impact in Acute Settings

Although RELiZORB’s benefits for chronic care patients is undeniable, the cartridge has also found use in acute care settings—like burn patients, pancreatitis surgeries, cancer treatment facilities, and other places where patients are subjected to enteral feeding.

As an example, Alcresta is partnering with a large Integrated Delivery Network (IDN). Initially, the client utilized RELiZORB to treat only chronic CF patients—both in-hospital and in the out-patient setting. Gradually, Alcresta’s enzyme-based product has found application across the client’s operations and was granted open formulary access. Alcresta is nowin the process of training staff across the hospital system through in-services and webinars.

As part of the project, Alcresta is also working with the healthcare company’s purchasing teams to make RELiZORB easily accessible for discharged patients. Since the client is an IDN and serves as an umbrella of insurance for its patients, RELiZORB “fits nicely” since patients carry insurance benefits both inside and outside the hospital premises. Be it the patient, provider, physician, dietician, or nurse, RELiZORB and its proven benefits are resonating across the entire spectrum of healthcare. To sustain the continuity of care Relizorb is ordered via EMR inpatient, and Alcresta provides a RELiZORB SUPPORT program to help the transition for outpatient access needs.

To sustain patient access to RELiZORB, a network of healthcare providers supporting patients with CF published a consensus statement in July’s edition of the Journal of Cystic Fibrosis. The statement was signed by over 60 healthcare providers (HCPs), including 45 distinguished CF specialty MDs, who treated 450 patients with RELiZORB. The consensus statement characterized RELiZORB as a “physiologically superior product,” with “proven success in a real-world setting,” which “can produce measurable, clinically relevant benefits.”

SBS Patients and their Heightened Needs

Clearly, Alcresta’s enzyme-based products are a boon for enterally-fed patients with chronic malabsorption conditions and depending on the formula taken, this includes patients with SBS, per Orlando. Unlike chronic CF patients who require partial enteral tube feeding, SBS patients can be 100 percent dependent on enterally-fed nutrients for their survival. Many of these patients are recovering from bowel resections due to infections, cancer or other rare diseases. As a result, they have a very short bowel and can’t efficiently absorb nutrients.

Presently, RELiZORB allows SBS patients to consume a daily total of 1L of enteral feeding formula—by connecting two 500mL cartridges with 1L of enteral nutrition daily. However, this will further improve in 2021 with the arrival of a 1,000mL advanced version of the immobilized lipase cartridge which is expected to facilitate the consumption of 2L of enteral feeding formula, giving adult CF patients, SBS patients and adult post-pancreatitis surgery patients more reasons to be optimistic about reaching an optimal level of nutrition. In addition to increased capacity, the 1,000 mL cartridge will be designed to handle a thicker, blenderized formula which could contain higher fiber formulas which are commonly used by patients with SBS. Another expected benefit of the 1,000mL cartridge is the reduction in time taken to consume nutrients as the design will allow for higher flow rates without sacrificing fat hydrolyzation.

Ready to Capitalize on the Momentum

The next generation of RELiZORB will mark a critical milestone in Alcresta’s roadmap. Already assigned to the B4105 HCPCS billing code effective January 1, 2019, and with a CE mark to boot, RELiZORB is expected to make a bigger impact as more insurance providers make the product accessible. As evidenced by the consensus report published in July, America’s CF community is firmly behind RELiZORB becoming the new standard of care for enterally-fed patients. In fact, the report cited RELiZORB as “a rational alternative to the historical but illogical current standard of care.” The signatories concluded in the report, “A new, effective tool is tantalizingly within reach, and we call on insurance providers to make it possible for us to use it.”

"We are uniquely positioned to be the market leader in what we consider to be a $3 billion malabsorption market in a variety of under-served orphan populations"

Consequently, Alcresta has ramped up its efforts to improve the product’s ease-of-access through various initiatives directed at the niche, ultra-orphan drug market. Since the ultra-orphan market struggles to get the attention of big sponsors, Alcresta has invested heavily in improving its case management hub service, to better navigate patients through payer channels. Alcresta expects the new service will help patients access the product and in petitioning payers to reflect the benefits of RELiZORB in Medical Policy. The new support team, called RELiZORB Support, will also ensure apt support for discharged patients, either through home therapy that lasts three months or through chronic care and access to RELiZORB.

Orlando is buoyant about the potential heights that Alcresta can reach in the coming years. “We are uniquely positioned to be the market leader in what we consider to be a $3 billion malabsorption market in a variety of under-served orphan populations,” states Orlando, who became the CEO of Alcresta in June 2019.

Although platform expansion, commercial growth, and financial stability are atop Alcresta’s objectives, Orlando and his team of 38 employees are reveling in the deeds that come with treating children suffering from chronic malabsorption. The satisfaction they get from working with critical needs patients and a host of dedicated HCPs supersedes everything else, according to Orlando, who was previously COO of Vericel Corporation, a giant in the arena of cell therapies. “I have worked on products where patients barely notice the direct benefits. However, with RELiZORB, the positive effects are both immediately palpable and long-term. The fact that we’re helping children every day drives us,” he concludes.

RELiZORB, which has a CE mark and an assigned B4105 HCPCS billing code, is already used by approximately 50 percentof all enterally-fed CF patients in the U.S.