CutisPharma Announces FDA Approval of Firvanq (vancomycin) for Treatment of Clostridium Difficile Associated Diarrhea and Staphylococcus Aureus Colitis

In continuation of my update on vancomycin

CutisPharma announced  the US Food and Drug Administration (FDA)  approval of  Firvanq (vancomycin hydrochloride) for oral solution, for the treatment of Clostridium difficile associated diarrhea and enterocolitis caused by Staphylococcus aureus, including methicillin-resistant strains.

“We are pleased to announce the FDA approval of Firvanq,” said Neal I. Muni, MD, MSPH, Chief Executive Officer of CutisPharma. “Firvanq's approval is an important step forward to providing patients the only FDA-approved vancomycin oral liquid treatment option for Clostridium difficile associated diarrhea, a life-threatening condition that affects over a half-million patients in the United States annually.”

Upon its launch, which is targeted to be April 2, 2018, Firvanq will replace CutisPharma’s FIRST®-Vancomycin Unit-of-Use Compounding Kit, which has been available to pharmacists that need a convenient, accurate, and compliant way to compound vancomycin oral liquid therapy. Firvanq will be commercially available in 25 mg/mL and 50 mg/mL strengths in convenient 150 mL and 300 mL sizes. Firvanq is designed to be easy to use and has the potential to be a cost-effective alternative to existing vancomycin therapies.

“As a practicing infectious disease physician treating many patients with CDAD, having an FDA-approved vancomycin oral liquid formulation that is affordable and accessible to my patients is very beneficial,” said Stuart Johnson, MD, Loyola University Medical Center. “Patient access is currently limited by the fact that only a select few pharmacies perform compounding in the outpatient setting these days, given the many new regulations in place. Availability of an FDA-approved vancomycin oral liquid treatment will effectively allow any pharmacy to stock this therapy, and hopefully encourage third-party payer reimbursement, significantly improving accessibility and convenience for patients.”

CutisPharma Announces FDA Approval of Firvanq (vancomycin) for Treatment of Clostridium Difficile Associated Diarrhea and Staphylococcus Aureus Colitis

FDA Approves Osmolex ER (amantadine) for the treatment of Parkinson’s Disease and Drug-Induced Extrapyramidal Reactions

 

In continuation of my update on amantadine

Osmotica Pharmaceutical US LLC, announced the  U.S. Food and Drug Administration (FDA) has approval Osmolex ER, an amantadine extended release tablet, for the treatment of Parkinson's disease and for the treatment of drug-induced extrapyramidal reactions in adult patients. Extrapyramidal symptoms are known side effects of many common medications.

“The FDA’s approval of Osmolex ER provides a new treatment option for those patients suffering from Parkinson’s disease and adults who have extrapyramidal reactions, or movement disorders, that are caused by certain medicines. We are eager to make Osmolex ER available to physicians and patients in the U.S.,” stated Brian Markison, Chief Executive Officer of Osmotica.

“We are currently finalizing our plans to commercialize the product and ensure patients and providers have access as soon as possible. We believe that the approved indications and compelling value proposition will be important factors in physician adoption and marketing of Osmolex ER,” added Markison.

Osmolex ER tablets, a proprietary drug formulation containing a combination of immediate release and extended release amantadine utilizing Osmotica’s patented Osmodex® technology, represents a new once-a-day approach to the treatment of Parkinson’s disease and drug-induced involuntary movements in adults. The Osmolex ER tablet is taken once-daily in the morning, releasing amantadine throughout the day. Physicians have three dosage options with 129 mg, 193 mg and 258 mg tablets, with a maximum daily dose of 322 mg, providing them with dosing flexibility for each patient.

Osmolex ER is protected by three formulation patents with protection extending through March 2030, with additional patent applications pending.

FDA Approves Osmolex ER (amantadine) for the treatment of Parkinson’s Disease and Drug-Induced Extrapyramidal Reactions

New class of antimicrobial polymers can kill five hard-to-treat multidrug-resistant bacteria

An international research team led by the Institute of Bioengineering and Nanotechnology (IBN) of the Agency for Science, Technology and Research (A*STAR) and IBM Research developed a synthetic molecule that can kill five deadly types of multidrug-resistant bacteria with limited, if any, side effects. Their new material could be developed into an antimicrobial drug to treat patients with antibiotic-resistant infections. This finding was reported in the scientific journal Nature Communications.

Superbugs that are resistant to antibiotics are a serious health threat. According to the UK Review on Antimicrobial Resistance, superbugs kill around 700,000 people worldwide each year. By 2050, 10 million people could die each year if existing antibiotics continue to lose their effectiveness.

“There is an urgent global need for new antimicrobials that are effective against superbugs. The situation has become more acute because bacteria are starting to develop resistance to the last-line antibiotics, which are given only to patients infected with bacteria resistant to available antibiotics,” said Professor Jackie Y. Ying, Executive Director of IBN.

The research community is trying to develop alternatives to antibiotics using synthetic polymers. However, the antimicrobial polymers developed so far are either too toxic for clinical use, not biodegradable or can only target one type of bacteria.

To address this problem, Dr Yi Yan Yang from IBN brought together a multidisciplinary research team from the US, China and Singapore to develop a new class of antimicrobial polymers called guanidinium-functionalized polycarbonates with a unique killing mechanism that can target a broad range of multidrug-resistant bacteria. It is biodegradable and non-toxic to human cells.

The polymer kills bacteria in the following way. First, the polymer binds specifically to the bacterial cell. Then, the polymer is transported across the bacterial cell membrane into the cytoplasm, where it causes precipitation of the cell contents (proteins and genes), resulting in cell death.

The team tested the polymers on mice infected with five hard-to-treat multidrug-resistant bacteria: Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureu and Pseudomonas aeruginosa. These superbugs are commonly acquired by patients in the hospitals and can cause systemic infections that lead to septic shock and multiple organ failure. The results showed that the bacteria were effectively removed from the mice and no toxicity was observed.

The researchers then further tested the effectiveness of the polymers on mice with two types of systemic infections caused by superbugs: peritonitis (an infection of the stomach’s inner lining) and lung infections from Pseudomonas aeruginosa. The polymers eliminated the bacterial infections in both groups of mice with negligible toxicity.

Dr Yi Yan Yang, Group Leader at IBN said:

We have demonstrated the first example of a biodegradable synthetic macromolecule with broad-spectrum antimicrobial activity in mice, unique killing mechanism and no toxicity. Once the polymer finishes its job of killing the bacteria, it will be naturally degraded after three days and will not remain in the body. This antimicrobial agent shows great promise for the treatment and prevention of multidrug-resistant systemic infections.

“This study illustrates the potential for this new research field we denote as ‘macromolecular therapeutics’ to create entirely new classes of treatments for multiple diseases,” said Dr James Hedrick, Distinguished Research Staff Member, IBM Research – Almaden, San Jose, California. “In 2016, we demonstrated the efficacy of synthetic polymers to combat deadly viral diseases. The current research for treating bacterial infections rounds out our ability to someday treat a spectrum of infectious diseases with a single, new type of mechanism without the onset of resistance.”

To determine whether the bacteria will develop any resistance to the polymer, the team collaborated with Dr Paola Florez de Sessions at A*STAR’s Genome Institute of Singapore and the Cell Engineering group of Dr Simone Bianco at IBM Research – Almaden to perform genomic analysis. They found that the bacteria did not show any resistance development even after multiple treatments with the polymer.

Ref :http://www.ibn.a-star.edu.sg/pdf/media_release/press_133.pdf

https://www.nature.com/articles/s41467-018-03325-6/figures/1

New class of antimicrobial polymers can kill five hard-to-treat multidrug-resistant bacteria

Antiviral drug not beneficial for reducing mother-to-child transmission of hepatitis B when added to existing preventatives

In continuation of my update on Tenofovir

Tenofovir disoproxil fumarate (TDF), an antiviral drug commonly prescribed to treat hepatitis B infection, does not significantly reduce mother-to-child transmission of hepatitis B virus when taken during pregnancy and after delivery, according to a phase III clinical trial in Thailand funded by the National Institutes of Health. The study tested TDF therapy in addition to the standard preventative regimen — administration of hepatitis B vaccine and protective antibodies at birth — to explore the drug’s potential effects on mother-to-child transmission rates. The results appear in the New England Journal of Medicine.

“Limited evidence of the benefit of using antiviral drugs to prevent mother-to-child transmission of hepatitis B has led to conflicting practice recommendations around the world,” said Nahida Chakhtoura, M.D., a study team member and medical officer at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). “Our study suggests that adding TDF to the current regimen seems to have little effect on infant infection rates when transmission rates are already low.”

To prevent infection, WHO recommends that all newborns receive their first dose of hepatitis B vaccine within 24 hours of delivery. Infants born to hepatitis B-infected mothers are also given protective antibodies called hepatitis B immune globulin (HBIG). However, mother-to-child transmission can still occur in women with high levels of virus in their blood, as well as those with mutated versions of the virus.

The current study was conducted at 17 hospitals of the Ministry of Public Health in Thailand. It screened more than 2,500 women for eligibility and enrolled 331 pregnant women with hepatitis B. The women received placebo (163) or TDF (168) at intervals from 28 weeks of pregnancy to two months after delivery. All infants received standard hepatitis B preventatives given in Thailand, which include HBIG at birth and five doses of the hepatitis B vaccine by age 6 months (which differs from the three doses given in the United States). A total of 294 infants (147 in each group) were followed through age 6 months.

Three infants in the placebo group had hepatitis B infection at age 6 months, compared to zero infants in the TDF treatment group. Given the unexpectedly low transmission rate in the placebo group, the researchers concluded that the addition of TDF to current recommendations did not significantly reduce mother-to-child transmission of the virus.

“We observed no treatment-related safety concerns for the mothers or infants and no significant differences in infant growth,” said the study’s lead author Gonzague Jourdain, M.D., Ph.D., of Thailand’s Chiang Mai University, the Harvard T.H. Chan School of Public Health and France’s IRD (Institut de recherche pour le développement). “These safety data also are relevant for pregnant women receiving TDF as part of HIV treatment or HIV pre-exposure prophylaxis.”

According to the study authors, the clinical trial had enough participants to detect statistical differences if the transmission rate in the placebo group reached at least 12 percent, a rate observed in previous studies. Though the reasons are unknown, the researchers speculate that the lower transmission rate seen in the study may relate to the number of doses of hepatitis B vaccine given to infants in Thailand, lower rates of amniocentesis and Cesarean section deliveries in this study, or the lower prevalence of mutated viruses that result in higher vaccine efficacy in Thailand compared to other countries.

Ref : http://www.nejm.org/doi/full/10.1056/NEJMoa1708131

Antiviral drug not beneficial for reducing mother-to-child transmission of hepatitis B when added to existing preventatives

Compound prevents neurological damage, shows cognitive benefits in mouse model of Alzheimer’s disease

The supplement nicotinamide riboside (NR) – a form of vitamin B3 – prevented neurological damage and improved cognitive and physical function in a new mouse model of Alzheimer’s disease. The results of the study, conducted by researchers at the National Institute on Aging (NIA) part of the National Institutes of Health, suggest a potential new target for treating Alzheimer’s disease. The findings appear in the Feb. 5, 2018, issue of Proceedings of the National Academy of Sciences.

NR acts on the brain by normalizing levels of nicotinamide adenine dinucleotide (NAD+), a metabolite vital to cellular energy, stem cell self-renewal, resistance to neuronal stress and DNA repair. In Alzheimer’s disease, the brain’s usual DNA repair activity is impaired, leading to mitochondrial dysfunction, lower neuron production, and increased neuronal dysfunction and inflammation.

“The pursuit of interventions to prevent or delay Alzheimer’s and related dementias is an important national priority,” said Richard J. Hodes, M.D., director of the NIA. “We are encouraging the testing of a variety of new approaches, and this study’s positive results suggest one avenue to pursue further.”

The international team of scientists was led by Vilhelm A. Bohr, M.D., Ph.D., senior investigator and chief of the Laboratory of Molecular Gerontology of the NIA’s Intramural Research Program, with Dr. Yujun Hou, a postdoctoral investigator in the laboratory.

Based on their studies in human postmortem brain, they developed a new strain of mice mimicking major features of human Alzheimer’s such as tau pathology, failing synapses, neuronal death and cognitive impairment. Using this animal model, the researchers tested the effects of an NR supplement by adding it to the drinking water of the mice. Over a three-month period, researchers found that mice who received NR showed reduced tau in their brains, but no change in amyloid-beta.

The NR-treated mice also had less DNA damage, higher neuroplasticity (activity and reorganization of brain cells associated with learning or memory), increased production of new neurons from neuronal stem cells, and lower levels of neuronal damage and death. In the hippocampus area of the brain – in which damage and loss of volume is found in people with dementia – NR seemed to either clear existing DNA damage or prevent it from spreading further.

The NR-treated mice also performed better than control mice on multiple behavioral and memory tests, such as water mazes and object recognition. NR mice also showed better muscular and grip strength, higher endurance, and improved gait compared to their control counterparts. The research team believes that these physical and cognitive benefits are due to a rejuvenating effect NR had on stem cells in both muscle and brain tissue.

“We are encouraged by these findings that see an effect in this Alzheimer’s disease model,” said Dr. Bohr. “We are looking forward to further testing of how NR or similar compounds might be pursued for their possible therapeutic benefit for people with dementia.”

Next steps for the research team include further studies on the underlying mechanisms and preparations towards intervention in humans.

The team’s work also included contributions from researchers at the Danish Aging Research Center at the University of Aarhus, and the Center for Healthy Aging at the University of Copenhagen. The Bohr lab has a Cooperative Research and Development Agreement -- which allows NIH investigators to join colleagues from industry and academia to pursue common research goals -- with ChromaDex Corp.

Compound prevents neurological damage, shows cognitive benefits in mouse model of Alzheimer’s disease

Aspirin as Good a Clot Buster as Pricey Drugs After Joint Replacement

Good old aspirin is just as effective as newer, expensive drugs at preventing blood clots after hip or knee replacement, a new clinical trial suggests.

Researchers said the findings could change some doctors' prescribing habits.

After knee or hip replacement surgery, there's a risk of blood clots in the legs or lungs. So it's routine for patients to take clot-preventing drugs for some time afterward.

Right now, some doctors choose powerful anti-clotting drugs like dabigatran (Pradaxa) and rivaroxaban(Xarelto), said Dr. David Anderson, the lead researcher on the new trial.

But it hasn't been clear whether those expensive prescription drugs are any better than cheap, readily available aspirin, explained Anderson, of Dalhousie University, in Halifax, Canada.

Based on the new findings, they're not.

Few patients in the study developed a blood clot after surgery, and those on aspirin fared just as well as those on rivaroxaban.

The caveat, Anderson said, was that all study patients received rivaroxaban for the first five days after surgery. After that, they either continued on the drug or switched to aspirin for another nine to 30 days.

"From this study, we have no evidence to support starting aspirin on day one," Anderson said.

But after day five, he added, "it's very reasonable to consider switching to aspirin."

Over the past decade, surgeons have already been turning away from powerful anticoagulants toward aspirin and non-drug options for thwarting clots, said Dr. Alejandro Gonzalez Della Valle.

Gonzalez Della Valle specializes in hip and knee surgery at the Hospital for Special Surgery in New York City.

These days, he said, patients have a generally low risk of blood clots after hip or knee replacement for a number of reasons. Those include shorter surgical times, and the use of regional anesthesia instead of general.

Clots can also be prevented by improving blood flow in patients' legs right after surgery. So getting patients on their feet and moving early on is key, Gonzalez Della Valle explained. Similarly, pneumatic compression devices can be used to encourage blood flow in the lower limbs while patients are in their hospital beds.

Dr. Kevin Bozic, a spokesperson for the American Academy of Orthopaedic Surgeons (AAOS), said that the AAOS guidelines already state that no one drug is better than another for preventing clots.

"This study reinforces that," Bozic said.

He agreed that most surgeons have been turning to aspirin in the past 10 years because recovery times are shorter and people leave the hospital much sooner. Most people can have just aspirin, but some at high risk of blood clots -- those with a history of clots, people who are very obese -- might need an anticoagulant, Bozic added.

"The strategy for preventing clots should include medication and early mobilization," he stressed.

Ref:http://www.nejm.org/doi/full/10.1056/NEJMoa1712746

Aspirin as Good a Clot Buster as Pricey Drugs After Joint Replacement - Drugs.com MedNews

Research shows link between fluoroquinolone antibiotics and increased risk of aortic disease

New research from a Swedish and Danish team of researchers led from Karolinska Institutet lend additional support to a link between treatment with fluoroquinolone antibiotics and an increased risk of acute aortic disease. The study is published in the esteemed journal The BMJ.

Fluoroquinolone antibiotics are used globally to treat a variety of infections. Recent observational studies have raised concerns that they may be associated with a more than twofold increase in the risk of acute and life-threatening aortic disease (aortic aneurysm or dissection). However, due to limitations in study design, it has not been possible to draw firm conclusions.

To assess whether there actually is a link, researchers from Karolinska Institutet and Lund University in Sweden and Statens Serum Institut in Denmark analysed data from Swedish national health registers. The researchers were then able to compare the risk of aortic aneurysm or dissection among more than 360,000 treatment episodes of fluoroquinolones with the risk among the same number of treatment episodes of amoxicillin, another type of antibiotic.

Research shows link between fluoroquinolone antibiotics and increased risk of aortic disease

High vitamin D levels may help prevent cancer

In continuation of my update on Vitamin D, 

The study reinforces the existing theory that vitamin D helps defend against certain cancers. Exposure to sunlight stimulates the production of vitamin D by our skin. Vitamin D contributes to calcium level maintenance in our bodies, which in turn helps teeth, muscles and bones remain healthy. Aside from established benefits of vitamin D on bone diseases, evidence continues to emerge that vitamin D could be effective for other cancers and chronic diseases.   

Yet more comprehensive research needs to be conducted, as to date, the majority of studies have been conducted throughout American and European populations, and more studies focusing on Asian populations are necessary.
It is vital to determine whether the effects are the same in non-Caucasian populations, since Vitamin D metabolism and concentrations differ dependant on ethnicity.
The study published by the BMJ was carried out to determine if vitamin D was linked to site specific and total cancer.

Data spanning nine public health centres across Japan was analysed, from 33,736 female and male participants between the ages of 40 and 69 years old.
Participants were required to disclose a comprehensive overview of their lifestyle, diet and medical history and have blood samples taken to assess their vitamin D levels. Factors such as seasons affected vitamin D levels; summer and autumn typically produced higher levels compared to spring or winter. Samples were then assigned to one of four groups, based on levels.

Researchers then monitored the study participants for a mean period of 16 years, during which 3,301 new cancer cases were registered.
Once multiple known cancer risk factors had been accounted for, including weight (BMI), physical activity, age, dietary factors, smoking and alcohol intake, researchers discovered that high levels of vitamin D  reduced the overall risk of cancer by 20% in both women and men.

Higher levels were linked to a 30-50% lower relative risk of liver cancer, and more so in men than women. No cancers exhibited a higher risk connected to high vitamin D levels, and there was no evidence of a link to prostate or lung cancer.
Adjustments were made for dietary and other factors to confirm the strength of the findings, but this did little to affect the results. One limitation of the study was an insufficient number of organ specific cancers. In addition, even with the risk factor adjustments, there is no absolute certainty that the results were skewed by unidentified factors.  For this reason, no concrete conclusions about cause and effect can be asserted.

The large sample size for overall cancer, large number of blood samples tested and the extensive follow up period were vital strengths of the study. The result reinforce the theory that vitamin D has a role in defending against the risk of cancer, but the authors emphasize that vitamin D may carry additional health benefits too, that were not measured in this study.  

Further studies are needed to clarify the optimal concentrations (of vitamin D) for cancer prevention."

Further studies are needed to clarify the optimal concentrations (of vitamin D) for cancer prevention."

Ref : https://www.eurekalert.org/pub_releases/2018-03/b-hvd030618.php

High vitamin D levels may help prevent cancer

Sorrento Therapeutics Subsidiary, Scilex, Receives FDA Approval for Non-Opioid ZTlido (lidocaine topical system) 1.8% for Post-Herpetic Neuralgia Pain

In continuation of my update on lidocaine

Sorrento Therapeutics, Inc. , received approval from the U.S. Food and Drug Administration (FDA) for ZTlido (lidocaine topical system) 1.8%. ZTlido is indicated for the relief of pain associated with post-herpetic neuralgia (PHN), also referred to as post-shingles pain. ZTlido is a major advancement in analgesics because of its proprietary adhesion technology demonstrating 12-hour wear with efficient lidocaine delivery, even during exercise.

“ZTlido was designed to solve a problem that is commonly reported with transdermal/topical patches: they don’t stay on. Based on the adhesion study results with ZTlido, we believe that ZTlido product will be welcomed by healthcare providers, patients and payers who are looking for an effective and efficient, local pain treatment,” said Dr. Henry Ji, Chairman and CEO of Sorrento and Scilex. “We also intend to explore the expansion of ZTlido into additional indications and the underlining platform technology of ZTlido for other active pharmaceutical ingredients (APIs) and combinations of APIs. As demonstrated by the NDA approval for ZTlido, our team successfully executed on our development plan for the product and now, looks forward to executing on our commercial and strategic alliance plans as well.”

“Topical lidocaine is an important option for healthcare providers to have in their armamentarium for treating PHN, a difficult-to-treat neuropathic pain,” stated Dr. Jeff Gudin, Director, Pain Management and Palliative Care, Englewood Hospital and Medical Center. “The Centers for Disease Control and Prevention’s guideline of non-opioid treatments for chronic pain recognizes topical lidocaine as an alternative first-line therapy. ZTlido now offers providers and patients this option.”

ZTlido’s anhydrous topical system is based on a novel technology that is designed to achieve superior adhesion and drug delivery efficiency. ZTlido only requires 36 mg/topical system versus 700 mg/patch of Lidoderm® (lidocaine patch 5%), the US reference product, to achieve the same therapeutic dose of drug. The safety and efficacy of ZTlido was bridged to Lidoderm in comparative pharmacokinetic studies that demonstrated bioequivalence between products.

According to an FDA report of the product quality of transdermal drug delivery systems, adhesion was the most widely reported quality defect of transdermal patches.¹ With a clear need for improved patch adhesion systems, ZTlido was specifically designed to maintain optimum skin contact throughout the 12-hour administration period. Adhesion is critical to the safety and efficacy quality of a topical system. Simply, the topical system must be in contact with skin to deliver the drug. ZTlido adhesion performance was demonstrated in a clinical study in fifty-four (54) healthy volunteers where forty-seven (47) subjects (87%) had adhesion scores of 0 (≥ 90% adhered; essentially no lift off the skin) for all evaluations performed every 3 hours during the 12 hours of administration, and seven (7) subjects (13%) had adhesion scores of 1 (≥ 75% to < 90% adhered; some edges only lifting off the skin) for at least one evaluation, and no subjects had scores of 2 or greater (< 75% adhered). In the same study 91% (49) of the subjects presented with a score of 0 at the end of the 12-hour administration period. The remaining 5 subjects had a score of 1.

In a separate Phase 1 comparative adhesion study in normal healthy subjects (n=44), ZTlido demonstrated superior adhesion (p <0.0001) to Lidoderm at 3 hours that improved over the 12-hour administration period.

According to recent IMS data, more than 100 million prescription lidocaine patches were sold in the US in 2017. Sorrento intends to have Scilex complete the final steps necessary to commercial launch of ZTlido in the US with the objective to make the product commercially available to patients sometime in 2018.

Sorrento Therapeutics Subsidiary, Scilex, Receives FDA Approval for Non-Opioid ZTlido (lidocaine topical system) 1.8% for Post-Herpetic Neuralgia Pain

Lilly Receives Additional FDA Approval for Verzenio (abemaciclib), as Initial Treatment for Advanced Breast Cancer

In continuation of my update on Abemaciclib

Eli Lilly and Company  announced the U.S. Food and Drug Administration (FDA) has approval of  Verzenio (abemaciclib) in combination with an aromatase inhibitor (AI) as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. This additional FDA approval marks the third indication for Verzenio within five months. In September 2017, Verzenio became the first and only cyclin-dependent kinase (CDK)4 & 6 inhibitor approved in combination and as a single agent in metastatic breast cancer. Specifically, Verzenio was approved for use in combination with fulvestrant for the treatment of women with HR+, HER2- advanced or metastatic breast cancer with disease progression following endocrine therapy, and as monotherapy for the treatment of adult patients with HR+, HER2- advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.

The recommended dose of Verzenio in combination with an AI is 150 mg orally twice daily, continued until disease progression or unacceptable toxicity. Verzenio is available in four tablet strengths (200 mg, 150 mg, 100 mg, and 50 mg).

This approval of Verzenio as initial therapy in combination with an AI is based on the efficacy and safety demonstrated in the pivotal MONARCH 3 clinical trial. MONARCH 3 is a Phase 3, randomized, double-blind, placebo-controlled trial evaluating Verzenio in combination with an AI as initial endocrine-based therapy that enrolled 493 postmenopausal women with HR+, HER2- advanced breast cancer who had no prior systemic treatment for advanced disease. In patients who received neoadjuvant/adjuvant endocrine therapy, a disease-free interval of more than 12 months since completion of endocrine therapy was required. This Verzenio new drug application was given Priority Review as part of the FDA's Expedited Programs for Serious Conditions, a program used for therapies that address an unmet medical need in the treatment of serious or life-threatening conditions, such as metastatic breast cancer. Verzenio was also granted Breakthrough Therapy Designation in 2015 based on the Phase 1 JPBA trial.

In MONARCH 3, Verzenio dosed orally at 150 mg twice daily on a continuous schedule with an AI demonstrated a greater than 28-month median progression-free survival (PFS) in patients who received initial endocrine-based therapy for metastatic disease (28.2 months [95% CI: 23.5-NR] vs 14.8 months [95% CI: 11.2-19.2] with placebo plus an AI [HR: 0.54; 95% CI: 0.418-0.698, P <0.0001]). In patients with measurable disease who received Verzenio plus an AI (n=267), an objective response rate of 55.4 percent was achieved (ORR; defined as complete response plus partial response [CR + PR], and based upon confirmed responses; PR defined as ≥30% reduction in target lesions)¹ (n=148; 95% CI: 49.5-61.4), with 52.1 percent of patients having achieved a PR (n=139) and 3.4 percent having achieved a CR (n=9).² In comparison, in the placebo-plus-AI group of patients with measurable disease (n=132), ORR was 40.2 percent (n=53; 95% CI: 31.8-48.5), with all women being partial responders. Median duration of response (DoR) was 27.4 months with Verzenio plus an AI (95% CI: 25.7-NR) versus 17.5 months with placebo plus an AI (95% CI: 11.2-22.2).

"This approval is an important milestone, as it shows that Verzenio plus an aromatase inhibitor substantially reduced tumor size and delayed disease progression in women with HR+, HER2- metastatic breast cancer. Notably, the MONARCH 3 trial included patients with certain concerning clinical characteristics, such as a pattern of disease that spread to the liver," said Joyce O'Shaughnessy, M.D., Celebrating Women Chair in Breast Cancer Research and chair, Breast Cancer Research Program, Baylor University Medical Center, Texas Oncology and U.S. Oncology, Dallas, TX. "This information will help inform treatment decisions for each patient, which can be complicated in advanced breast cancer."

The labeling for Verzenio contains warnings and precautions for diarrhea, neutropenia, hepatotoxicity, venous thromboembolism, and embryofetal toxicity. Instruct patients at the first sign of loose stools to initiate antidiarrheal therapy, increase oral fluids, and notify their healthcare provider. Perform complete blood counts and liver function tests prior to the start of Verzenio treatment, every two weeks for the first two months, monthly for the next two months, and as clinically indicated. Based on results, Verzenio may require dose modification. Monitor patients for signs and symptoms of thrombosis and pulmonary embolism and treat as medically appropriate. Advise patients of potential risk to a fetus and to use effective contraception. See full Prescribing Information for further management instructions. The most common adverse reactions in the MONARCH 1, 2, and 3 trials (all grades, ≥20%) were diarrhea, neutropenia, nausea, abdominal pain, infections, fatigue, anemia, leukopenia, decreased appetite, vomiting, headache, alopecia, and thrombocytopenia.

"The speed with which our team has been able to work with the FDA to gain approval for this additional Verzenio indication underscores Lilly's commitment to delivering meaningful medicines that can help more people living with advanced breast cancer," said Sue Mahony, Ph.D., senior vice president and president of Lilly Oncology. "Verzenio has now been developed, studied and clinically proven in three key trials to be effective for women with HR+, HER2- metastatic breast cancer – helping to ensure we are providing support to those who need it most."

"For those facing a diagnosis of metastatic breast cancer or learning that their disease has spread further, each new indication and clinical development is critical," said Marc Hurlbert, Ph.D., chairman, Metastatic Breast Cancer Alliance. "Today's news represents continued progress towards helping more people living with this devastating disease."

Lilly Receives Additional FDA Approval for Verzenio (abemaciclib), as Initial Treatment for Advanced Breast Cancer