3 AM, halfway through a graveyard shift at the hospital. Adrenaline coursed through my body. The announcement meant a patient was having a medical emergency. Code blue usually referred to a cardiac problem; I needed to prepare.

I hurried to the back of the pharmacy and grabbed my medication kit. I took one last glance at the depleted stock on the pharmacy shelves and hurried upstairs.

30 minutes later our patient still remained unstable. The intensivist continued to call out for medications, especially IV sodium bicarbonate. I watched my stock dwindle.

Normally I would call down to the pharmacy, and they would send up more. But due to a national shortage of the drug, there was no more. The doctor kept ordering sodium bicarbonate, sometimes 2 vials at once. He wiped out the supply in the code cart and my med kit, forcing me to dip into the “emergency supply” stuffed into my jacket pockets.

I gently reminded him about the shortage, always tough to do when someone’s life was at stake, and I have never forgotten his reply. He demanded to know why such a common product was on backorder, and couldn’t pharmacy just make some. “Couldn’t we go lick some rocks and find the stuff?” His joke lightened the tense mood, but it got me thinking.

What factors led to scarcity in medications? And could I use my expertise as a pharmacist to alleviate the situation?

What Causes Drug Shortages?

It’s actually quite mysterious. According to data from the University of Utah Drug Information Service, in 2019 an astonishing 82% of shortages were listed as reason unknown. The other causes include manufacturing, discontinuation, raw materials, and supply and demand.

Manufacturing

Manufacturing reasons are varied and encompass plant shutdowns, factories not passing quality assurance inspections, and product recalls.

A few years ago, our hospital experienced a major potassium phosphate shortage. We could not get the stuff, causing last-minute reformulations of the TPN nutritional support IV bags administered to patients who could not eat.

What was the reason cited by the manufacturer? Glass particles discovered in a few batches, prompting a recall, stock-outs, and subsequent shortage of the alternative agent, sodium phosphate.

Eventually, we obtained enough potassium phosphate to replenish our stock, but the problems didn’t end there. The pharmacy staff was instructed to filter every vial of potassium phosphate before adding it to a diluent; no matter which manufacturer we received it from. We also took the extra step of instructing nurses to run the potassium phosphate using tubing with an in-line filter.

This practice was enforced by every hospital I worked at for years after the initial event. One would think the problem would be resolved by now, but we were never given clear guidelines. We kept on filtering, happy to have the product back in stock.

Discontinuation

Discontinuation of products is often due to a lack of profitability. Physicians stop prescribing the old generic drugs; who can resist the marketing influence of flashy new ones? Or, sadly, the medication might treat a rare condition. that only affects a small percentage of the population.

Often manufacturers give no advanced notice. We only know when our pharmacy buyers attempt to order a medication, and it doesn’t come in.

One example popular with the OB anesthesiologists was injectable caffeine citrate. They used it for patients with epidural related headaches. I can’t remember the last time I saw it in stock, but I still receive occasional inquisitive calls. There simply isn’t a good alternative.

Raw Materials

My introductory story is a frightening example of when a compound used to produce medication is in short supply. Scarcity at the bottom level of production can halt the entire supply chain. The problem worsens when raw materials come from other countries. In fact, the U.S. imports around 80% of bulk or raw materials. Contamination, shipping delays, and devastation of crops of plants used to extract medication can all cause disruption.

Supply and Demand

Lack of supply with increased demand is a big cause of our current coronavirus shortages. Unfortunately, our two biggest drug suppliers are India and China, both countries struggling with their own response to the coronavirus.

The pandemic compounded the problem of drug shortages already on the rise. As of June, the FDA reported over 200 drugs on a shortage, with five classes of drugs being the most critical: CNS, antimicrobials, cardiovascular, ophthalmic, and chemotherapy. The first three groups are especially important for COVID-19 patients. These include medications a critically ill patient in the intensive care unit would need: sedatives and paralytics for intubation, analgesics to combat pain, and vasopressors and cardiac medications to support heart rate and blood pressure.

The sudden influx of COVID-19 patients places an unprecedented strain on an already tenuous system. According to medical technology manufacturer BD’s internal data:

“Hospitals in hot spots see between a 150% and 600% increase in demand for drugs like propofol, fentanyl, hydromorphone, midazolam and neuromuscular blockers.”

Natural disasters can also play a role in supply reduction. In September of 2017, Hurricane Maria decimated Puerto Rico, cutting off our hospital’s main supplier of large volume IV bags. Suddenly bags of normal saline and sterile water were a hot commodity.

What Are the Consequences of Drug Shortages?

Aside from the major cost of delayed or omitted treatments and therapies to patients, there are unseen costs as well.

Pharmacists must have a plan for every back-ordered drug. An alternative, often a less desirable agent, is located, ordered, prepared for use (e.g. hospital barcoding, sterile compounding), stocked, and the hospital staff educated. This takes a tremendous toll on time and cost, not to mention stress and tension between departments.

When we were short on the pain medication Dilaudid, our pharmacy ordered bulk vials and spent hours each day drawing up individual doses. We gave these syringes short expiration dates which meant stocking supply on the units was always a challenge. Certain departments, I’m looking at you ER, would always run out while others wouldn’t use their stock, and it would need to be wasted.

Medication errors would increase as well. Often we could only order a different concentration of a drug, or a vial which always had a light blue cap would now have a green one, leading to mix-ups and incorrect doses given. In fact, a 2017 ISMP survey showed nearly a quarter of respondents were aware of a drug shortage-related med error.

Possible Solutions.

So what can be done about drug shortages? Unfortunately, from a hospital pharmacy perspective, not much. It often seems we extinguish the small fires without ever managing the source. But we do have a few options.

Pharmacists continually research alternatives- second, third, even fourth-line agents. Working with P&T committees, we place restrictions on certain medications even if it means not all patients will receive the drug they need. The FDA has granted extended beyond-use dating for certain medications, and our tireless pharmacy technicians compound from a bulk supply like never before.

Thankfully, the one thing never in short supply is great people. Supportive co-workers assist and never stop caring. It’s our job and we love it.

The post Drug Shortages During the Time of Coronavirus appeared first on Medika Life.

Hepion Introduces ‘AI-POWR^TM‘ Proprietary Big Data Analytics Platform in AMBITION Trial

• AI – Artificial Intelligence, using supervised and unsupervised machine learning
• P – Precision Medicine, individualizing treatments based on genetics, environment, and lifestyle
• O – Omics, including genomics, proteomics, lipidomics, and metabolomics
• W – World, accessing world genomic databases
• R – Response and clinical outcomes

DATE OF RELEASE: AUGUST 5, 2020

EDISON, NJ / ACCESSWIRE /  Hepion Pharmaceuticals, Inc. (NASDAQ:HEPA), a biopharmaceutical company focusing on the development of therapeutic drugs for the treatment of liver disease arising from non-alcoholic steatohepatitis (“NASH”), today announced that CRV431 was administered to the first NASH patient. Hepion previously announced that CRV431 successfully progressed through a phase 1 program, where the safety, tolerability and pharmacokinetics of CRV431 were evaluated in healthy subjects.

The open-label phase 2a study, called the ‘AMBITION’ trial, is designed to assess safety, tolerability, and pharmacokinetics of 75 mg CRV431, administered orally to F2 and F3 NASH patients (n=18), once daily for 28 days. Additionally, our Clinical Pharmacology group will be examining certain biomarkers including, for example, collagen, matrix metalloproteinases, lipidomics, genomics, liver transaminases, Pro-C3, ELF score, gene-gene, gene-protein network analysis, and Fibroscan in a multivariate multi-omics analysis to elucidate CRV431 activity in NASH. AI-POWR, Hepion’s in-house proprietary big data analytics platform that allows for precision medicine will be used to optimize the understanding of CRV431 in NASH.

“Our phase 2a trial is a relatively small study of 28-days duration with CRV431 dosing in NASH patients,” said Dr. Patrick Mayo, Hepion’s Senior Vice-President, Clinical Pharmacology. “The primary endpoint of this trial assesses safety, tolerability, and pharmacokinetics. From a secondary endpoint perspective, we are not looking to see histological changes in fibrosis in such a short period of time. However, we believe our proprietary big data analytical platform which integrates clinical pharmacology with bioinformatics, systems pharmacology, and machine learning will allow us to rapidly identify meaningful outcomes that can be used in future clinical trials. This proprietary platform has already been applied to previous studies, for example, where we conducted a genetic analysis of over 28,000 genes and variants in a prior study of CRV431 in human Precision Cut Liver Slices obtained from Fibrofind in the UK. This method of data analytics has allowed us to enrich our current phase 2a study design.”

Dr. Robert Foster, Hepion’s Chief Executive Officer added, “By its very nature, drug development is a risky venture but is absolutely necessary. In particular, we believe NASH is a very heterogenous disease with complex biochemical and pathological processes complicated, for example, by time and genetics. As such, treating NASH may be tantamount to hitting a moving target. We believe we can mitigate much of the usual risks associated with clinical trials, and NASH in particular, by utilizing cutting edge data tools allowing for precision medicine. We will be drawing upon our vast expertise in cyclophilin drug development, honed over decades of experience, to further the advancement of CRV431 in the clinic. Dr. Mayo and our research group have developed a highly sophisticated and proprietary analytics program, called AI-POWR, to make the most of our non-clinical and clinical data in a way that is a novel step forward.”

Dr. Stephen Harrison, Principal Investigator and Hepion’s consultant Medical Director, further commented, “I find Hepion’s unique approach, utilizing big data analytics in a phase 2a NASH trial with AI, personally very exciting and should allow us to further drill down into this complex disease. There are no other cyclophilin inhibitors, such as CRV431, that are currently being used in this patient population. As such, Hepion’s CRV431 represents an entirely novel approach to treating this serious disease.”

About Hepion Pharmaceuticals

Hepion Pharmaceuticals is a clinical stage biopharmaceutical company focused on the development of targeted therapies for liver disease arising from non-alcoholic steatohepatitis (NASH) and other types of hepatitis. The Company’s lead drug candidate, CRV431, reduces liver fibrosis and hepatocellular carcinoma tumor burden in experimental models of NASH. Preclinical studies also have demonstrated antiviral activities towards HBV, HCV, and HDV through several mechanisms. These diverse therapeutic activities result from CRV431’s potent inhibition of cyclophilins, which are involved in many disease processes. Currently in clinical phase development, CRV431 shows potential to play an important role in the overall treatment of liver disease – from triggering events through to end-stage disease

Forward-Looking Statements
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimated,” and “intend,” among others. These forward-looking statements are based on Hepion Pharmaceuticals’ current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, substantial competition; our ability to continue as a going concern; our need for additional financing; uncertainties of patent protection and litigation; risks associated with delays, increased costs and funding shortages caused by the COVID-19 pandemic; uncertainties with respect to lengthy and expensive clinical trials, that results of earlier studies and trials may not be predictive of future trial results; uncertainties of government or third party payer reimbursement; limited sales and marketing efforts and dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. As with any drug candidates under development, there are significant risks in the development, regulatory approval, and commercialization of new products. There are no guarantees that future clinical trials discussed in this press release will be completed or successful, or that any product will receive regulatory approval for any indication or prove to be commercially successful. Hepion Pharmaceuticals does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in Hepion Pharmaceuticals’ Form 10-K for the year ended December 31, 2019 and other periodic reports filed with the Securities and Exchange Commission.

For further information, please contact:
Stephen Kilmer
Hepion Pharmaceuticals Investor Relations
Direct: (646) 274-3580
skilmer@hepionpharma.com

The post First NASH Patient Dosed with CRV431 in Phase 2 ‘AMBITION’ Clinical Trial appeared first on Medika Life.

DATE OF RELEASE: June 22, 2020

EDISON, NJ / ACCESSWIRE /  Hepion Pharmaceuticals, Inc. (NASDAQ:HEPA) (“Hepion” or the “Company”), a biopharmaceutical company focused on the development of therapeutic drugs for the treatment of liver disease arising from non-alcoholic steatohepatitis (“NASH”), today announced results from a study of the Company’s lead drug candidate, CRV431, demonstrating antifibrotic activity in an experimental model of renal fibrosis.

The study, which was conducted by SMC Laboratories in Tokyo, Japan, evaluated CRV431 in the Unilateral Ureteral Obstruction (“UUO”) mouse model. Mice that underwent left ureter surgical ligation were orally administered either vehicle or CRV431 at a dose of 50 mg/kg/day for two weeks (n=8 mice/group). A third group of eight mice, the Sham group, did not undergo surgery and did not receive drug treatment. The fibrotic scarring in response to the UUO procedure was visualized by Sirius red staining of histological sections from the affected kidneys. Quantitation of the Sirius red staining at the end of the study demonstrated that kidney fibrosis was significantly elevated in vehicle treated UUO mice, compared to the Sham group. Kidney fibrosis in the CRV431 treated group was 42% lower as compared to vehicle treated mice (p=0.0006).

“CRV431 has exerted antifibrotic activity in a number of in vitro and in vivo studies conducted by independent research laboratories in the United States, United Kingdom, France, and Japan,” stated Dr. Daren Ure, Hepion’s Chief Scientific Officer. “These included five studies in the “STAM™” and “Western Diet” mouse models of NASH; two studies of liver fibrosis induced by liver toxins; and two separate ex vivo studies of explanted human liver and lung tissues. Notably, the explanted lung tissue study in which CRV431 was efficacious used lung tissue obtained from a patient with idiopathic pulmonary fibrosis. The latest findings in this kidney study further confirm that CRV431 decreases fibrotic scarring in multiple organs, regardless of etiology.”

Dr. Robert Foster, Hepion’s Chief Executive Officer, commented, “To date, every one of our preclinical studies has consistently demonstrated CRV431’s antifibrotic activity. In addition to inhibiting cyclophilins, which play a critical role in the formation of collagen, CRV431 down-regulates gene expression and decreases production and secretion of proteins important to fibrosis. As such, we are advancing what we believe to be a direct-acting antifibrotic molecule in the clinic for the treatment of NASH, which represents a novel approach within the NASH landscape of investigational drugs.”

About Hepion Pharmaceuticals

Hepion Pharmaceuticals is a clinical stage biopharmaceutical company focused on the development of targeted therapies for liver disease arising from non-alcoholic steatohepatitis (NASH) and other types of hepatitis. The Company’s lead drug candidate, CRV431, reduces liver fibrosis and hepatocellular carcinoma tumor burden in experimental models of NASH. Preclinical studies also have demonstrated antiviral activities towards HBV, HCV, and HDV through several mechanisms. These diverse therapeutic activities result from CRV431’s potent inhibition of cyclophilins, which are involved in many disease processes. Currently in clinical phase development, CRV431 shows potential to play an important role in the overall treatment of liver disease – from triggering events through to end-stage disease.

Forward Looking Statements

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimated,” and “intend,” among others. These forward-looking statements are based on Hepion Pharmaceuticals’ current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, substantial competition; our ability to continue as a going concern; our need for additional financing; uncertainties of patent protection and litigation; risks associated with delays, increased costs and funding shortages caused by the COVID-19 pandemic; uncertainties with respect to lengthy and expensive clinical trials, that results of earlier studies and trials may not be predictive of future trial results; uncertainties of government or third-party payer reimbursement; limited sales and marketing efforts and dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. As with any drug candidates under development, there are significant risks in the development, regulatory approval, and commercialization of new products. There are no guarantees that future clinical trials discussed in this press release will be completed or successful, or that any product will receive regulatory approval for any indication or prove to be commercially successful. Hepion Pharmaceuticals does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in Hepion Pharmaceuticals’ Form 10-K for the year ended December 31, 2019 and other periodic reports filed with the Securities and Exchange Commission.

For further information, please contact:

Stephen Kilmer
Hepion Pharmaceuticals Investor Relations
Direct: (646) 274-3580
skilmer@hepionpharma.com

The post Hepion Pharmaceuticals’ CRV431 Demonstrates Efficacy in Kidney Fibrosis appeared first on Medika Life.