Saturday, January 30, 2021

Sitagliptin Promising Addition for Preventing Acute GVHD

In continuation of my updates on sitagliptin 

For patients undergoing myeloablative allogeneic hematopoietic stem cell transplantation, sitagliptin combined with tacrolimus and sirolimus results in a low incidence of grade II to IV acute graft-versus-host disease (GVHD) by day 100, according to a study published in the Jan. 7 issue of the New England Journal of Medicine.

Sherif S. Farag, M.D., Ph.D., from the Indiana University School of Medicine in Indianapolis, and colleagues conducted a phase 2 clinical trial to examine the reduction in incidence of grade II to IV acute GVHD from 30 percent to no more than 15 percent by day 100 with sitagliptin plus tacrolimus and sirolimus. Thirty-six patients received myeloablative conditioning followed by mobilized peripheral-blood stem cell transplants from matched related or unrelated donors.

The researchers found that by day 100, acute GVHD occurred in two of 36 patients. The incidence of grade II to IV GVHD and of grade III or IV GVHD was 5 and 3 percent, respectively. At one year, nonrelapse mortality was zero. The one-year cumulative incidence of relapse was 26 percent, and for chronic GVHD, it was 37 percent. At one year, GVHD-free, relapse-free survival was 46 percent. Toxic effects were similar to those seen in patients undergoing allogeneic stem cell transplantation.

"Inhibition of dipeptidyl peptidase 4 should be further investigated in randomized trials that compare sitagliptin with current standard GVHD prophylaxis regimens," the authors write.

Friday, January 29, 2021

Statins May Protect Heart From Chemo for Early Breast Cancer

In continuation of my update on statins 

For women with early breast cancer treated with anthracyclines, statin exposure is associated with a lower risk for hospital presentation for heart failure, according to a study published online Jan. 6 in the Journal of the American Heart Association.

Husam Abdel-Qadir, M.D., Ph.D., from the Women's College Hospital in Toronto, and colleagues conducted a retrospective cohort study involving women aged 66 years and older without prior heart failure who received anthracyclines or trastuzumab for newly diagnosed early breast cancer. Using propensity scores, statin-exposed and unexposed women were matched in a 1:1 ratio. Data were included for 666 statin-discordant pairs of anthracycline-treated women and 390 pairs of trastuzumab-treated women.

The researchers found that the five-year cumulative incidence of heart failure hospital presentations after anthracyclines was 1.2 percent (95 percent confidence interval [CI], 0.5 to 2.6 percent) and 2.9 percent (95 percent CI, 1.7 to 4.6 percent) in statin-exposed and unexposed women, respectively (P = 0.01). In the anthracycline cohort, the cause-specific hazard ratio associated with statins was 0.45 (95 percent CI, 0.24 to 0.85; P = 0.01). The five-year cumulative incidence of heart failure hospital presentations after trastuzumab was 2.7 percent (95 percent CI, 1.2 to 5.2 percent) and 3.7 percent (95 percent CI, 2.0 to 6.2 percent) in statin-exposed and unexposed women, respectively (P = 0.09), with a cause-specific hazard ratio associated with statins of 0.46 (95 percent CI, 0.20 to 1.07; P = 0.07).

"This study does not conclusively prove statins are protective," Abdel-Qadir said in a statement. "However, this study builds on the body of evidence suggesting that they may have benefits."

Thursday, January 28, 2021

Alzheimer's disease drug may help fight against antibiotic resistance

In continuation of my update on PBT2

Researchers from The University of Queensland, The University of Melbourne and Griffith University have discovered that the drug called PBT2 is effective at disrupting and killing a class of bacteria -- known as Gram-negative bacteria -- that cause infections such as pneumonia, bloodstream infections and meningitis.

UQ's Professor Mark Walker said the metal transport drug may offer a last line of defence against some of the world's most difficult to treat superbugs.

"The emergence of antibiotic-resistant superbugs is an urgent threat to human health, undermining the capacity to treat patients with serious infection," Professor Walker said.

"Alternative strategies to treat such multi-drug resistant bacteria are urgently needed.

"Led by UQ's Dr David De Oliveira, our team hypothesised that, by using this experimental Alzheimer's treatment to disrupt the metals inside these bacteria, we would also disrupt their mechanisms of antibiotic resistance.

"This was shown to be the case, with the Alzheimer's drug -- combined with the antibiotic polymyxin -- successfully tackling antibiotic-resistant superbugs like Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli."

Griffith University's Professor Mark von Itzstein AO from the Institute for Glycomics said the new treatment was effective, and offered a range of other benefits.

"Based on its use as an experimental Alzheimer's treatment, there's been a significant amount of solid science done on this drug already," Professor von Itzstein said.

"We know, for example, that clinical studies of PBT2 show that it is safe for use in humans.

"And, given that we've been able to combine it with the antibiotic polymyxin to treat polymyxin-resistant bacteria, we may be able to make other now-ineffective antibiotics become effective again for treating infectious diseases.

"This could resharpen, so to speak, some of the weapons we thought we'd lost in our fight against antibiotic-resistant bacteria."

The University of Melbourne's Associate Professor Christopher McDevitt, from the Peter Doherty Institute for Infection and Immunity (Doherty Institute), said the drug had already proved effective beyond the petri dish.

"Animal studies show that the combination of polymyxin and PBT2 kills polymyxin-resistant bacteria, completely clearing any infection," Associate Professor McDevitt said.

"Hopefully in the not-too-distant future people will be able to access this type of treatment in the clinic.

"New techniques are critical in addressing this building threat to human health, and this treatment is an additional weapon in our arsenal to fight the accelerating threat of antibiotic resistance.

"If these new solutions aren't developed, it's estimated that by 2050, antimicrobial-resistant bacteria will account for more than 10 million deaths per year.

"This new treatment could help turn the tide on antibiotic resistance."

Wednesday, January 27, 2021

Lorlatinib Superior to Crizotinib for ALK-Positive NSCLC

In continuation of my update on lorlatinib and  crizotinib



Among patients with previously untreated advanced ALK-positive non-small cell lung cancer (NSCLC), progression-free survival is significantly longer for those who receive first-line therapy with lorlatinib versus crizotinib, according to a study published in the Nov. 19 issue of the New England Journal of Medicine.

Alice T. Shaw, M.D., Ph.D., from the Massachusetts General Hospital Cancer Center in Boston, and colleagues conducted a global, randomized, phase 3 trial comparing lorlatinib with crizotinib in 296 patients with advanced ALK-positive NSCLC who were previously untreated for metastatic disease.

The researchers found that 78 and 39 percent of patients in the lorlatinib group and crizotinib group, respectively, were alive without disease progression at 12 months (hazard ratio for disease progression or death, 0.28). An objective response occurred in 76 and 58 percent of those in the lorlatinib and crizotinib groups, respectively. Among those with measurable brain metastases, an intracranial response occurred in 82 and 23 percent, respectively; an intracranial complete response occurred in 71 percent of those who received lorlatinib. Hyperlipidemia, edema, increased weight, peripheral neuropathy, and cognitive effects were the most common adverse events associated with lorlatinib. Compared with crizotinib, lorlatinib was associated with more grade 3 or 4 adverse events (mainly altered lipid levels; 72 versus 56 percent).

"Among patients with previously untreated, advanced ALK-positive NSCLC, those who received lorlatinib had significantly longer progression-free survival, a higher overall and intracranial response, and better quality of life than those who received crizotinib," the authors write.

Several authors disclosed financial ties to pharmaceutical companies, including Pfizer, which manufactures lorlatinib and funded the study.

Tuesday, January 26, 2021

New effective and safe antifungal isolated from sea squirt microbiome

The new molecule was discovered in the microbiome of a sea squirt from the Florida Keys as part of an effort to identify novel antimicrobials from understudied ecosystems. Scientists named the antifungal turbinmicin, after the sea squirt from which it was isolated, Ecteinascidia turbinate.

Disease-causing fungi continue to evolve resistance to the small number of drugs available to thwart them. As a result, more people are dying from previously treatable diseases, such as candidiasis or aspergillosis, which are caused by common fungi that sometimes turn virulent. Identifying compounds like turbinmicin is key to developing new and effective drugs. However, while turbinmicin is a promising drug candidate, additional study of the molecule and extensive preclinical research must be performed before a new drug can become available.

A collaboration of chemists, biologists, and physicians from UW-Madison published their findings Nov. 19 in the journal Science. The discovery of turbinmicin is the most tangible output yet of the group's five-year, $30 million grant from the National Institutes of Health to glean useful new antimicrobial drugs from bacteria living in overlooked environments.

The majority of existing antimicrobials were isolated from soil-dwelling bacteria. As scientists continued probing these bacteria for new drugs, they often turned up the same molecules over and over again.

"Bacteria in particular are rich sources of molecules. But a lot of the terrestrial ecosystems have been pretty heavily mined for drug discovery," says Tim Bugni, a professor in the UW-Madison School of Pharmacy who led the turbinmicin project. "There's immense bacterial diversity in the marine environment and it's barely been investigated at all."

To correct for that oversight, Bugni partnered with UW School of Medicine and Public Health infectious disease professor David Andes, UW-Madison bacteriology professor Cameron Currie, and their colleagues to search neglected ecosystems. Specifically, they sought to discover novel bacteria from marine animals and then screen them for new kinds of antimicrobial compounds.

To identify turbinmicin, the research team began by collecting ocean-dwelling invertebrates from the Florida Keys between 2012 and 2016. From these animals, they identified and grew nearly 1,500 strains of actinobacteria, the same group of bacteria that has produced many clinical antibiotics. Using a screening method, they prioritized 174 strains to test against drug-resistant Candida, an increasingly prominent and dangerous disease-causing fungus. Turbinmicin stood out for its effectiveness.

"Candida auris in particular is pretty nasty," says Bugni. Nearly half of patients with systemic Candida infection die. "The Candida auris strain we targeted in this paper is resistant to all three classes" of existing antifungals.

The researchers tested purified turbinmicin against a slate of 39 fungi isolated from patients. These strains both represented diverse species and encompassed all the known ways that fungi have evolved resistance to existing drugs. In lab experiments, turbinmicin halted or killed nearly all fungal strains at low concentrations, indicating a potent effect.

Similar experiments in mice infected with drug-resistant strains of Candida auris and Aspergillus fumigatus also demonstrated turbinmicin's ability to attack resistant fungi. Because fungi and animals are closely related, and thus share similar cellular machinery, antifungals can prove toxic to animals as well. Yet, turbinmicin did not show toxic side effects in mice, even at concentrations 1000 times higher than the minimum dose. The effective dose would work out to tens of milligrams for an average-weight adult, less than for many other antibiotics.

Based on experiments in yeast led by UW-Madison genetics professor Anjon Audhya, turbinmicin appears to target the cellular packaging and organizational system of fungi. Turbinmicin blocks the action of the protein Sec14p, with the end result that yeast like Candida cannot bud to reproduce. Other kinds of fungi, when exposed to turbinmicin, may have a difficult time shuttling cellular contents around to grow.

The researchers have submitted a patent for turbinmicin and have now turned their attention to improving the molecule by making small alterations to its structure that could increase its effectiveness as a drug. The discovery of turbinmicin also serves as a proof-of-concept for the collaboration's efforts to explore new ecosystems and screen thousands of candidates to identify new, effective antimicrobial candidates.

"Now we have the tools to sort through candidates, find promising strains and produce molecules to do animal studies," says Bugni. "That's the key for targeting multi-drug resistance: you need unique molecules."

Monday, January 25, 2021

Xofluza Approved for Postexposure Prevention of Flu

In continuation of my update on Baloxavir marboxil (BXM)

The approved indication for Xofluza (baloxavir marboxil) has been expanded to include postexposure prevention of influenza for those who may have come in contact with someone who has the flu, the U.S. Food and Drug Administration announced Monday.

Xofluza was approved in 2018 to treat uncomplicated flu in patients 12 years and older who are symptomatic for no more than two days. The drug was previously only available in a tablet form but is now available in granule form for mixing in water.

The expanded approval decision was based on data from the Phase III BLOCKSTONE study, a randomized, double-blind, controlled trial of 607 individuals ages 12 years and older who were exposed to a household member with the flu. Individuals were randomly assigned to receive either a single dose of Xofluza (303 individuals) or placebo (304 individuals). One percent of those who received Xofluza compared with 13 percent who received placebo were infected with influenza and presented with fever and at least one respiratory symptom over 10 days. These data were published in the New England Journal of Medicine in July.

The most commonly reported side effects of Xofluza include diarrhea, bronchitis, nausea, sinusitis, and headache.

"This expanded indication for Xofluza will provide an important option to help prevent influenza just in time for a flu season that is anticipated to be unlike any other because it will coincide with the coronavirus pandemic," Debra Birnkrant, M.D., director of the Division of Antiviral Products in the FDA Center for Drug Evaluation and Research, said in an agency news release. "Americans will have to be more vigilant than ever as these viruses spread concurrently."

Saturday, January 23, 2021

Researchers identify three drugs as possible therapeutics for COVID-19

In continuation of my update on Amodiaquine and nebivolol




Based on virtual and in vitro antiviral screening that began in the earlier months of the COVID-19 pandemic, the researchers led at UTHSC by Colleen Jonsson, PhD, identified zuclopenthixol, nebivolol, and amodiaquine as promising therapeutics for the virus in its early stages.

Dr. Jonsson is a professor and the Endowed Van Vleet Chair of Excellence in Virology in the College of Medicine at UTHSC. She also directs the UTHSC Regional Biocontainment Laboratory (RBL), where this research was conducted. The university's RBL is one of roughly a dozen federally funded labs authorized to safely study contagious pathogens.

In a paper published in ACS Pharmacology & Translational Science, the researchers propose the drugs as possible candidates for testing in future clinical trials to improve immune response to the virus. Amodiaquine is an older antimalarial, zuclopenthixol is an antipsychotic, and nebivolol is a blood pressure medication.

"Particularly in the context of this pandemic, there is a stringent need for high-quality studies that can provide critical knowledge concerning the COVID-19 disease and reliable treatment proposals," the paper states. "With these caveats in mind, we conceived a computational workflow that included independent in vitro validation, followed by assessing emerging candidates in the context of available clinical pharmacology data with the aim of proposing suitable candidates for clinical studies for early stage (incubation and symptomatic phases) patients infected by SARS-CoV-2."

"Given the need for improved efficacy and safety, we propose zuclopenthixol, nebivolol, and amodiaquine as potential candidates for clinical trials against the early phase of the SARS-CoV-2 infection," the researchers wrote.

Comparing the drugs to hydroxychloroquine, the anti-malarial drug most-frequently studied in clinical trials for use as a COVID-19 therapeutic, the researchers examined 4,000 approved drugs and found these three to act similarly to the hydroxychloroquine, and in some cases, more safely. The research indicates they may also improve efficacy when combined in lower doses with remdesivir, an anti-viral given an emergency use authorization by the United States Food and Drug Administration as a therapeutic for COVID-19.

"Think of it as a whack-a-mole game," said Tudor Oprea, MD, PhD, professor of Medicine and Pharmaceutical Sciences, chief of the UNM Division of Translational Informatics, and corresponding author on the paper. "Instead of having one hammer, you have two hammers, which is more effective. We're trying to give the scientific community two hammers, instead of one."

Dr. Jonsson added, "This is a very exciting discovery and we are following up on the potential use of zuclopenthixol, nebivolol, and amodiaquine in additional research studies."

FDA Approves Zokinvy (lonafarnib) for Hutchinson-Gilford Progeria Syndrome and Processing-Deficient Progeroid Laminopathies

Eiger BioPharmaceuticals, Inc. (Nasdaq:EIGR), focused on the development and commercialization of targeted therapies for serious rare and ultra-rare diseases, announced  the U.S. Food and Drug Administration (FDA)  approval of  Zokinvy (lonafarnib) for the treatment of Hutchinson-Gilford Progeria Syndrome (HGPS or Progeria) and processing-deficient Progeroid Laminopathies (PL).  

Progeria and Progeroid Laminopathies are separate and distinct ultra-rare, genetic, premature aging diseases that accelerate mortality in young patients.  Disease manifestations include growth failure, loss of body fat and hair, aged-looking skin, stiffness of joints, hip dislocation, generalized atherosclerosis, cardiovascular disease and stroke.  Untreated children with Progeria die of heart disease at an average age of 14.5 years.  There are 20 children and young adults with Progeria and PL identified and followed in the U.S.  

Zokinvy is a disease-modifying agent that has demonstrated a statistically significant survival benefit in children and young adults with Progeria.  In patients with Progeria, Zokinvy reduced the incidence of mortality by 60% (p=0.0064) and increased average survival time by 2.5 years.  The most commonly reported adverse reactions were gastrointestinal (vomiting, diarrhea, nausea), and most were mild or moderate (Grade 1 or 2) in severity.  Many Progeria patients have received continuous Zokinvy therapy for more than 10 years.

The increase in survival observed with Zokinvy was derived from two open-label clinical trials (N=62) conducted at Boston Children's Hospital.  The survival analysis compared Zokinvy-treated versus Zokinvy-naïve subjects with Progeria born in or after 1991, by age, gender, and geographic location. Zokinvy-naïve patients originated from a separate natural history study (n=81) conducted by The Progeria Research Foundation.

With this approval, the FDA issued a Rare Pediatric Disease Priority Review Voucher (PRV) to Eiger.  The Rare Pediatric Disease Priority Review Voucher program is designed to encourage development of new drugs and biologics for the prevention or treatment of rare pediatric diseases.  Eiger plans to sell the PRV and under the terms of the Collaboration and Supply Agreement with the Progeria Research Foundation (PRF) will share the proceeds equally with PRF.

"The FDA approval of Zokinvy is the result of a pioneering partnership between Eiger BioPharmaceuticals and PRF to bring the first approved therapy to children, young adults and families living with this devastating disease," said David Cory, President and CEO of Eiger.  "We are very proud that the first drug approval at Eiger confers a survival benefit to patients with one of the most ultra-rare, and ultimately fatal, pediatric diseases.  We are extremely grateful to all the children, young adults and their families who have made this possible through participation in the Zokinvy clinical trials."

"The approval of this breakthrough therapy is a critical milestone for the Progeria community and also for Eiger," said Thomas Dietz, PhD, Chairman of the Board at Eiger.  "The Eiger Board congratulates and commends the management team for their incredible dedication leading the company through its first NDA filing and approval, a major accomplishment for Eiger."

PRF Medical Director, Leslie Gordon, MD, PhD, added, "Shortly after our son, Sam, was diagnosed with Progeria, my family and I founded The Progeria Research Foundation to find the cause, treatments, and cure for all children with this fatal disease.  This first approved medication is a truly incredible milestone for the Progeria community as we forge ahead toward finding the cure.  We are thrilled to have Eiger as a partner in bringing Zokinvy to the approval finish line, and for their commitment to ensuring patient access to Zokinvy moving forward."

In support of the patient and healthcare provider community, Eiger is launching our dedicated service center, Eiger OneCare™.  This specialized team will offer personalized support, financial assistance, and access to Zokinvy, all designed for Progeria and processing-deficient Progeroid Laminopathy patients.  Eiger OneCare™ will be available Monday through Friday from 9 AM to 5 PM Eastern Time at 1-833-MYEIGER (1-833-693-4437).

FDA Approves Zokinvy (lonafarnib) for Hutchinson-Gilford Progeria Syndrome and Processing-Deficient Progeroid Laminopathies

Friday, January 22, 2021

FDA Approves Eysuvis (loteprednol etabonate) Ophthalmic Suspension for the Short-Term Treatment of the Signs and Symptoms of Dry Eye Disease

Kala Pharmaceuticals, Inc. (NASDAQ:KALA), a biopharmaceutical company focused on the discovery, development and commercialization of innovative therapies for diseases of the eye,  announced   the U.S. Food and Drug Administration (FDA) approval of Eysuvis (loteprednol etabonate ophthalmic suspension) 0.25% for the short-term (up to two weeks) treatment of the signs and symptoms of dry eye disease.

“The FDA approval of Eysuvis as the first prescription therapy specifically developed to address the short-term treatment needs of people living with dry eye disease is a major accomplishment for Kala and an important moment for patients, who have been waiting for an FDA-approved, safe, effective and fast-acting therapy,” said Mark Iwicki, Chairman, President and Chief Executive Officer of Kala Pharmaceuticals. “As we prepare to launch Eysuvis, we will leverage our strong foundation of highly experienced ophthalmology marketing, sales and market access professionals with the goal of establishing Eysuvis as the preferred, first-line prescription therapy for dry eye disease. We’d like to thank the many patients and investigators that were involved in the clinical trials that led to this important milestone.”

Dry eye disease is a chronic, episodic, multifactorial disease affecting the tears and ocular surface, and can involve tear film instability, inflammation, discomfort, visual disturbance and ocular surface damage. Approximately 80 percent of people living with dry eye disease suffer from episodic flares. These flares can be caused by a wide variety of triggers and often cannot be adequately managed with current therapies.

Eysuvis utilizes Kala’s AMPPLIFY® mucus-penetrating particle (MPP) Drug Delivery Technology to enhance penetration of loteprednol etabonate (LE) into target tissue on the ocular surface. LE targets the immune responses that drive acute dry eye disease flares. Prior to Eysuvis, there were no FDA-approved ocular corticosteroids for the treatment of dry eye disease. Kala Pharmaceuticals plans to launch Eysuvis in the U.S. by year-end.

“The approval of Eysuvis ushers in a new era in the treatment of dry eye disease and offers promise to the millions of dry eye patients who experience acute exacerbations, or flares, of their disease each year,” said Edward Holland, M.D., Director of Cornea Services at Cincinnati Eye Institute and Professor of Ophthalmology at the University of Cincinnati. “For the first time we will be able to offer dry eye patients a therapeutic option that provides rapid relief for both the signs and symptoms of the disease and that is safe and well tolerated.”

“Dry eye disease can significantly decrease quality-of-life among affected patients and drive decreased workplace productivity, contact lens intolerance and discontinuation, and poor cataract and refractory surgery outcomes,” said Kelly Nichols, O.D., M.P.H., Ph.D., F.A.A.O., Dean of the University of Alabama at Birmingham School of Optometry. “As the prevalence of dry eye disease increases, there is a tremendous need for new therapies to manage mild-to-moderate dry eye disease patients, many of whom currently go untreated. I am excited by the approval of EYSUVIS and confident that having access to an approved corticosteroid specifically for dry eye disease will meaningfully impact the management of patients across the U.S.”

The FDA granted approval to Eysuvis based on results from four clinical trials, including three Phase 3 trials and one Phase 2 trial, that demonstrated significant improvements in both the signs and symptoms of dry eye disease. Specifically, statistical significance was achieved after two weeks of dosing for the sign endpoint of conjunctival hyperemia in all three Phase 3 trials. Statistical significance was observed in two of the three Phase 3 trials for the symptom endpoints of ocular discomfort severity in both the overall intent-to-treat (ITT) population and in a predefined subgroup of ITT patients with more severe ocular discomfort at baseline. Eysuvis was well-tolerated across the four trials, with adverse events and intraocular pressure increases comparable to that observed with vehicle.

Thursday, January 21, 2021

FDA Approves Sutab (sodium sulfate, magnesium sulfate, and potassium chloride) Tablets for Colonoscopy Preparation

Sebela Pharmaceuticals®  announced  the U.S. Food and Drug Administration (FDA) approval of  Sutab® (sodium sulfate, magnesium sulfate, and potassium chloride) tablets. Sutab, a sulfate-based tablet preparation for colonoscopy, was developed and will be marketed by Braintree Laboratories, the makers of SUPREP® Bowel Prep Kit (sodium sulfate, potassium sulfate and magnesium sulfate) Oral Solution—the market leader in branded colonoscopy preparations.1 Sutab gives patients and physicians an alternative to liquid-based colonoscopy preparations. Braintree, a leader in gastroenterology, is part of Sebela Pharmaceuticals.

Colonoscopy is the most common detection method for colorectal cancer, a leading cause of cancer-related deaths that can be managed more effectively through screening.2  It is considered the gold standard of colorectal cancer screening methods for its ability to view the entire colon and both detect and remove polyps during the same procedure.3,4 Nineteen million colonoscopies are performed in the U.S. every year.5 For those patients, particularly those who have had difficulty completing colonoscopy preparation in the past, Sutab presents a welcome alternative to liquid bowel preparation.

"Successful bowel prep is critical for gastroenterologists to clearly see any polyps or abnormalities, yet the immense volume of liquid prep solutions can prevent patients from adequately completing their regimens. Tablets provide a welcome alternative for successful prep completion and visualization of the colon," said Douglas K. Rex, M.D., Director of Endoscopy at Indiana University Hospital and Professor, Department of Medicine, Division of Gastroenterology and Hepatology, University of Indiana School of Medicine.

Alan Cooke, President and CEO of Sebela Pharmaceuticals, said, "Gastroenterologists and their patients have repeatedly asked for a safe and efficacious tablet bowel prep. Now patients can benefit from SUTAB, thanks to Braintree's innovative and dedicated team, who have worked tirelessly to develop this important product.  SUTAB's FDA approval underscores Braintree's more than 35-year commitment to gastroenterology."

In two pivotal trials, 92% of patients achieved successful bowel cleansing with SUTAB6 and 92%-95% of patients achieved successful cleansing in all segments of the colon, including the proximal colon. 7 In one pivotal trial, 91% of patients rated Sutab as very easy to tolerable to consume.7 Seventy-eight percent said they would request Sutab again for a future colonoscopy.7  Fifty-two percent of all Sutab and MoviPrep®8 patients reported at least one selected gastrointestinal adverse reaction. 6 More SUTAB patients reported experiencing nausea and vomiting than the comparator, with ≤1% of these reports considered severe. 6

"The approval of Sutab provides a welcome relief for patients who struggle with the unpleasant taste issues commonly associated with other products for colonoscopy preparation," said Jack A. Di Palma, M.D., Professor of Medicine and Fellowship Program Director of the Division of Gastroenterology at the University of South Alabama College of Medicine and Past-President of the American College of Gastroenterology. "And because SUTAB contains the active sulfate ingredients similar to SUPREP, gastroenterologists will already be familiar with its effects."

Wednesday, January 20, 2021

FDA Approves Alkindi Sprinkle (hydrocortisone oral granules) for Pediatric Adrenocortical Insufficiency

In continuation of my update on hydrocortisone 

Eton Pharmaceuticals, Inc (Nasdaq: ETON), a specialty pharmaceutical company focused on developing and commercialising innovative treatments for rare pediatric diseases,  announced the U.S. Food and Drug Administration (FDA)   approval of  Alkindi Sprinkle (hydrocortisone) oral granules as replacement therapy for Adrenocortical Insufficiency (AI) in children under 17 years of age. Alkindi Sprinkle is the first and only FDA-approved granular hydrocortisone formulation for the treatment of adrenocortical insufficiency specifically designed for use in children.

“The FDA approval of Alkindi Sprinkle is a breakthrough for patients and caregivers treating pediatric adrenocortical insufficiency. We are excited to offer an FDA-approved product that enables low dosing and administration of hydrocortisone to pediatric patients,” said Sean Brynjelsen, CEO of Eton Pharmaceuticals. “We look forward to making the product available to patients in the coming months.”

“For years, we heard from parents about their struggle to provide the right dose to their child,” said Dina M. Matos, Executive Director of the CARES Foundation. “We are thrilled the FDA has approved Alkindi Sprinkle for pediatric patients with Adrenocortical Insufficiency including patients with Congenital Adrenal Hyperplasia, a type of Adrenocortical Insufficiency.”

The FDA approval of Alkindi Sprinkle was supported by six clinical studies, including the first and only interventional Phase III study of oral hydrocortisone for Pediatric AI in neonates to children under eight years of age. Prior to the approval of Alkindi Sprinkle, oral hydrocortisone was only FDA-approved in tablet formulations of 5mg and stronger. Many pediatric patients require significantly lower doses and the flexibility of precision titration. Alkindi Sprinkle will be available in 0.5mg, 1mg, 2mg, and 5mg strengths, allowing clinicians greater flexibility to individualize dosing based on each patient’s needs in accordance with the instructions for dosage and administration.

Eton expects Alkindi Sprinkle to be commercially available in the fourth quarter of 2020.

Tuesday, January 19, 2021

FDA Approves Gavreto (pralsetinib) for the Treatment of Adults With Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY),  announced  the U.S. Food and Drug Administration (FDA) approval of Gavreto (pralsetinib) for the treatment of adults with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test. This indication was approved under the FDA’s accelerated approval program based on data from the Phase I/II ARROW study. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Gavreto is a once-daily, oral precision therapy designed to selectively target RET alterations, including fusions and mutations.

“The FDA approval of Gavreto for RET fusion-positive non-small cell lung cancer is an important step towards our goal of providing an effective treatment option for every person diagnosed with lung cancer, no matter how rare or hard-to-treat their type of disease,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “We remain committed to finding personalized treatment options for people with cancer based on specific genomic or molecular alterations, and we look forward to partnering with Blueprint Medicines to further explore the potential of Gavreto across multiple RET-altered tumor types.”

RET-activating fusions and mutations are key disease drivers in many cancer types, including NSCLC and medullary thyroid cancer (MTC), and treatment options that selectively target these genetic alterations are limited. In NSCLC, RET fusions represent approximately 1-2% of patients. Biomarker testing for these fusions is the most effective way to identify people who are eligible for treatment with Gavreto.

The approval is based on the results from the Phase I/II ARROW study, in which Gavreto produced durable clinical responses in people with RET fusion-positive NSCLC with or without prior therapy, and regardless of RET fusion partner or central nervous system involvement. Gavreto demonstrated an overall response rate (ORR) of 57% (95% CI: 46%, 68%) and complete response (CR) rate of 5.7% in the 87 people with NSCLC previously treated with platinum-based chemotherapy, and the median duration of response (DoR) was not reached (95% CI: 15.2 months, not reached). In the 27 people with treatment-naïve NSCLC, the ORR was 70% (95% CI: 50%, 86%) with an 11% CR rate. The most common adverse reactions (≥25%) were fatigue, constipation, musculoskeletal pain and increased blood pressure (hypertension).

Gavreto is now the sixth FDA-approved medicine in Genentech’s portfolio of treatments for lung cancer. The FDA granted Breakthrough Therapy Designation to Gavreto for the treatment of RET fusion-positive NSCLC that has progressed following platinum-based chemotherapy and for RET mutation-positive MTC that requires systemic treatment and for which there are no acceptable alternative treatments.

The FDA has also granted Priority Review to Gavreto for the treatment of people with advanced or metastatic RET-mutant MTC and RET fusion-positive thyroid cancer, and is expected to make a decision on approval by February 28, 2021. This New Drug Application (NDA) was accepted for review under the FDA’s Real-Time Oncology Review (RTOR) pilot program, which aims to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible.

For those who qualify, Blueprint Medicines will offer patient assistance programs for people prescribed Gavreto by their doctor through YourBlueprint™ . Please visit or contact 1-888-BLUPRNT for more information.

Monday, January 18, 2021

FDA Approves Sesquient (fosphenytoin sodium) for the Treatment of Status Epilepticus in Adult and Pediatric Patients

Sedor Pharmaceuticals, LLC (Sedor) announced the U.S. Food and Drug Administration (FDA) spproval of  Sesquient (fosphenytoin sodium for injection) for the treatment of status epilepticus in adult and pediatric patients.

According to Neurocritical Care Society Guidelines, status epilepticus, which is classified as a single epileptic seizure lasting more than five minutes or two or more seizures within a five-minute period, must be treated quickly since irreversible brain damage or death may result if cessation of seizure is not achieved within 60 minutes of onset. Ready-to-dilute and room temperature stable, Sesquient is the only FDA-approved fosphenytoin that allows point-of-care storage, as well as fast and efficient administration in emergency rooms, intensive care units, first responder vehicles, and long-term care facilities, where serial seizures such as status epilepticus are most commonly treated.

“Status epilepticus is associated with irreversible neurologic damage and death, both of which largely depend on the seizure duration before initial treatment,” stated Barry Frankel, Chief Business Officer and co-founder of Sedor. “At some hospitals, it can take up to 30 minutes to get a status epilepticus drug from the pharmacy to the point of care in the ER to treat a patient. Sesquient – the first and only FDA-approved room temperature stable fosphenytoin – could help health care providers quickly treat status epilepticus patients and potentially reduce hospital costs associated with this condition.”

“This is an important milestone for Sedor Pharmaceuticals and opens a significant global market for the company. As our first NDA approved drug, Sesquient validates our business model of efficient development of critical care hospital injectable products,” added John Sedor, Chairman, CEO and co-founder of Sedor. Mr. Sedor added “While Sesquient is available in pre-filled liquid vials, this is a multi-dosage platform which we believe will be followed by a pre-filled IV bag. With this achievement completed, we are turning our focus to the development of our second product, Meloxicam for injection solubilized with betadex sulfobutyl ether sodium, for the potential treatment of acute post-surgical pain.”

Sedor is actively engaged in discussions to license the rights to Sesquient for North America, Europe, and other territories except for the Peoples Republic of China, where it has already been successfully licensed. Concurrently, Sedor is in discussions on securing capital to retain North American rights and commercialize the product.

Saturday, January 16, 2021

FDA Approves Detectnet (copper Cu 64 dotatate injection) Positron Emission Tomography (PET) Agent

RadioMedix Inc. and its commercial partner Curium announced the approval of  Detectnet (copper Cu 64 dotatate injection)  by the U.S. Food and Drug Administration (FDA).  Detectnet is a positron emission tomography (PET) agent indicated for the localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adult patients.  Curium expects to launch Detectnet immediately with doses available through various nuclear pharmacies or directly from Curium.   

RadioMedix Inc. and its commercial partner Curium announced today that Detectnet (copper Cu 64 dotatate injection) was approved by the U.S. Food and Drug Administration (FDA).  Detectnet is a positron emission tomography (PET) agent indicated for the localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adult patients.  Curium expects to launch Detectnet immediately with doses available through various nuclear pharmacies or directly from Curium.   

“Detectnet brings an exciting advancement in the diagnosis of neuroendocrine tumors for healthcare providers, patients, and their caregivers,” said Ebrahim Delpassand, MD, CEO of RadioMedix.  “The Phase III results demonstrate the clinical sensitivity and specificity of Detectnet which will provide a great aid to clinicians in developing an accurate treatment approach for their NET patients.  Perhaps most exciting is that the 12.7-hour half-life allows Detectnet to be produced centrally and shipped to sites throughout the U.S.  This will help alleviate shortages or delays that have been experienced with other somatostatin analogue PET agents.” 

“Curium is excited to bring the first commercially available Cu 64 diagnostic agent to the U.S. market.  Our unique production capabilities and distribution network allow us to deliver to any nuclear pharmacy, hospital or imaging center its full dosing requirements first thing in the morning, to provide scheduling flexibility to the institution and its patients,” said Curium CEO, North America, Dan Brague.  “We look forward to joining with healthcare providers and our nuclear pharmacy partners to bring this highly efficacious agent to the market.”      

“Detectnet brings an exciting advancement in the diagnosis of neuroendocrine tumors for healthcare providers, patients, and their caregivers,” said Ebrahim Delpassand, MD, CEO of RadioMedix.  “The Phase III results demonstrate the clinical sensitivity and specificity of Detectnet which will provide a great aid to clinicians in developing an accurate treatment approach for their NET patients.  Perhaps most exciting is that the 12.7-hour half-life allows Detectnet to be produced centrally and shipped to sites throughout the U.S.  This will help alleviate shortages or delays that have been experienced with other somatostatin analogue PET agents.” 

“Curium is excited to bring the first commercially available Cu 64 diagnostic agent to the U.S. market.  Our unique production capabilities and distribution network allow us to deliver to any nuclear pharmacy, hospital or imaging center its full dosing requirements first thing in the morning, to provide scheduling flexibility to the institution and its patients,” said Curium CEO, North America, Dan Brague.  “We look forward to joining with healthcare providers and our nuclear pharmacy partners to bring this highly efficacious agent to the market.”

Friday, January 15, 2021

FDA Approves Qdolo (tramadol hydrochloride) Oral Solution for the Management of Severe Pain

In continuation of my update on tramadol 

Bioscience, LLC, a specialty pharmaceutical company, announced today that the U.S. Food and Drug Administration (FDA) has approved Qdolo™ (tramadol hydrochloride) Oral Solution 5mg/1mL C-IV, an opioid agonist indicated in adults for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

According to the Centers for Disease Control and Prevention, 50 million adults in the United States have chronic daily pain, with 19.6 million adults experiencing high-impact chronic pain that interferes with daily life or work activities. A May, 2019 U.S. Department of Health and Human Services report on pain management best practices emphasized the need for an "individualized, patient-centered" approach for the treatment of pain.1

"As an oral liquid, Qdolo gives physicians flexibility to titrate dosing precisely according to individual patients' needs," said Jeff Bryant, President and CEO of Athena Bioscience. "In addition, for patients with swallowing disfunction (dysphagia) or who simply have trouble swallowing pills, Qdolo provides an essential alternative to other forms of tramadol." Qdolo has a patent pending.