Medness Plus 

In the current edition of Medness Plus, Esha Sehanobish updates you about the latest pharma news from Janssen, Novartis, GlaxoSmithKline, Eisai, Leo Pharma and Bayer in areas of HIV, Chronic Obstructive Pulmonary Disease (COPD), Obesity, Alzheimer’s and Malaria along with a major acquisition news in the prescription dermatology area. Also in this edition is the news about an Abbvie-backed biotech start-up that has three potential drugs in the form of antibodies that could cross the blood-brain barrier for the treatment of Alzheimer’s. Wondering which start-up that is? Read on to know more in this infographic-packed edition of Medness.- Abhi Dey

FDA approves the once a day HIV drug, Symutza from Janssen, to treat adult HIV patients.

The Johnson and Johnson’s pharmaceutical Janssen drug unit announced recently that FDA approved SYMUTZA, the first and only complete darunavir-based once a day tablet routine for the treatment of the Human Immunodeficiency Virus-type 1. This is supposed to be active in virologically suppressed adults and treatment-naïve patients [1].

Janssen receives #FDA approval for SYMTUZA™ (darunavir/cobicistat/emtricitabine/tenofovir alafenamide). Learn more: https://t.co/fGLUoO7X3S. See full PI incl. BOXED WARNING: https://t.co/aO0MEpOWL8 pic.twitter.com/SyZn0TuHv9

— JanssenUS (@JanssenUS) July 18, 2018

SYMUTZA is a combination of darunavir and a formulation which J & J claims increases the tolerability along with the luxury of it being administered in a single dose [2]. The approval was based on the data from two 48-week, pivotal phase 3, inferiority studies. Two studies were conducted to determine different factors about the drug. The EMERALD study evaluated virologically suppressed adults whereas the AMBER study focused mainly on the safety and efficacy of the drug compared to a controlled routine in adults. From these studies, it was shown that the drug was well tolerated in patients who were essentially 95% reaching and maintaining virologic suppression. Nevertheless, there is a black box warning regarding the worsening of acute Hepatitis B, post-treatment. SYMUTZA has been cleared in an already competitive market of many drugs that make adherence easier. The European Commission and Health Canada have already cleared this drug for treatment of HIV infection in adults and adolescents aged 12 years and older with a body weight of at least 40kg.

“For more than 25 years, Janssen has been committed to the research and development of transformational medical innovation across the continuum of HIV care. The FDA approval of SYMTUZA™ marks another important milestone in our quest to address real-world clinical challenges, combat HIV drug resistance and meet the diverse needs of those living with HIV,” said Brian Woodfall, M.D., Global Head of Late Development, Infectious Diseases, Janssen Pharmaceutical NV.

FDA advisory committee fails to back GSK’s NUCALA to treat COPD.

GlaxoSmithKline plc (NYSE: GSK) recently announced the decision of their Food and Drug Administration’s Pulmonary Allergy Drugs Advisory Committee, for the use of Nucala (mepolizumab) as an addition to inhaled corticosteroid-based maintenance treatment in patients suffering from COPD (chronic obstructive pulmonary disease) which is often guided by blood eosinophil counts [3]. The final count of vote was 3(for) and 16(against), thus leading to the decline of the proposal at this point. Even though the decision went against the company, a vote count regarding safety was primarily in their favor with 17-for and 2-against the use of mepolizumab. However, at this time, more data has been requested to determine what the target audience of this drug would be.

FDA refuses Nucala for COPD. Root of the matter is distinguishing asthma from COPD. Do we know that METREX and METREO patients didn’t have asthma? Perhaps the question is by the time you have fixed obstrn w/o reversibility, does it matter? #dutchhypothesis https://t.co/DfRkYpH9cR

— Samir Gupta (@SammyG_MD) July 27, 2018

Chronic obstructive pulmonary disease is a disease that is characterized by chronic inflammation in the lungs, by obstruction in airflow, exacerbations and breathlessness. The acute exacerbations are characterized by decreasing lung functions and a decline in health-related quality of life. An overproduction of eosinophils could cause inflammation in the vital organs and tissues thus permanently damaging them. The eosinophil counts could hence result in the exacerbation of COPD-linked symptoms. Mepolizumab serves as a monoclonal antibody that binds to IL-5. In this mechanism, once the drug binds, IL-5 can no longer attach itself to its receptors on the eosinophil surface thus reducing the level of eosinophil in blood. Mepolizumab, under the trade name Nucala, has been approved for an add-on treatment for severe eosinophilic asthma, in US and Europe.

“Having participated in today’s advisory committee meeting and heard the recommendation, we will continue to work with the FDA to address outstanding questions. We remain confident our data supports mepolizumab as a targeted treatment for patients continuing to experience COPD exacerbations guided by blood eosinophil count,” said Dave Allen, SVP Respiratory Therapy Area, R&D, GSK. If it eventually gets approved, Nucala (mepolizumab) will be the first to treat COPD. It was originally approved in 2015 as an add-on kind of a treatment for patients 12 years or older who suffered from severe asthma. It was after this that GlaxoSmithKline decided to extend its application to COPD.

FDA approves Krintafel (tafenoquine) for the treatment of vivax malaria.

GlaxoSmithKline and Medicines for Malaria Venture recently announced that FDA has approved under priority review, a single-dose Krintafel (tafenoquine) for the radical treatment of patients suffering from Plasmodium vivax malaria and who are 16 years or older, receiving proper antimalarial therapy for the infection [4]. There was a comprehensive global clinical development program on P. vivax radical cure that was carried out and was based on guidelines and agreements from FDA. By radical cure, one refers to the use of a drug that targets the dormant liver forms of the parasite and is administered with the available anti-malarial drugs such as chloroquine or artemisinin-based combination therapy.

#FDA approves Krintafel for P. vivax #malaria prevention in teens, adults https://t.co/KrGxpySxFn @ASTMH @GSK pic.twitter.com/7FGutTLpwa

— ID in Children (@IDinChildren) July 25, 2018

800 subjects were given the 300mg single-dose as a part of the randomized, double-blind studies, DETECTIVE Part 1 and Part 2 (TAF112582) and GATHER (TAF116564). In June 2017 the results of these Phase III trials were announced. The final data submitted studies on 4000 trial subjects who were exposed to the 300mg single-dose and other doses of tafenoquine. The safety and efficacy was then determined from these studies. The parasite, Plasmodium vivax is an organism that affects both humans and mosquitoes. Once the parasite infects the host, it passes through the blood and causes malaria. It can even be present in the liver in the dormant form (hypnozoite) and can periodically cause a relapse of P. vivax generated malaria. Hence this parasite is dangerous since it can lead to multiple bouts of the disease even when a new mosquito bite is not involved. Often the relapse can take place in days, weeks or even years. Most of the available anti-malarial treatment cannot treat this dormant form of parasite in the liver. Krintafel (tafenoquine) is an 8-aminoquinoline derivative that is the only FDA approved drug that has been found to be effective against all the stages of the P. vivax even hypnozoites. Medicines for Malaria Ventures and GSK entered into a collaboration to develop tafenoquine as a treatment for relapse in patients suffering from P. vivax malaria. “Today’s approval of Krintafel, the first new treatment for Plasmodium vivax malaria in over 60 years, is a significant milestone for people living with this type of relapsing malaria. Together with our partner, Medicines for Malaria Venture, we believe Krintafel will be an important medicine for patients with malaria and contribute to the ongoing effort to eradicate this disease,” said Dr. Hal Barron, Chief Scientific Officer and President of Research and Development, GSK.

Eisai announced positive results for their anti-obesity agent, BELVIQ.

Eisai recently conducted a study called CAMELLIA (Cardiovascular And Metabolic Effects of Lorcaserin In Overweight And Obese Patients) TIMI-61 [5]. The primary goal was to evaluate the effects of BELVIQ on the incidence of major adverse cardiovascular effects (MACE). The trial reached its primary safety objective based on which BELVIQ, upon long-term use, does not increase the incidence of MACE in overweight and obese patients who are at a higher risk of developing cardiovascular diseases. As a result, BELVIQ now becomes the first-ever weight-loss medication approved for weight management that has been achieved by a long-term cardiovascular outcome trial.

#Belviq is safe for the heart. https://t.co/M7Jo84PDUI https://t.co/7kY1BEUWRB

— Scott Isaacs, M.D. (@scottisaacsmd) July 23, 2018

BELVIQ is an adjunct to increased physical activity and reduced-calorie diet in adults whose BMI (Body mass index) of 30 kg/m² (obese) or 27 kg/m² (overweight) in presence of at least one of the following, hypertension, type 2 diabetes, dyslipidemia. CAMELLIA TIMI-61 was the largest placebo-controlled, double-blind, parallel-group Phase IIIB/IV study among weight loss medications. It consisted of 12000 overweight and obese patients with either established cardiovascular disorder or those that are at a high risk of developing it. This study was conducted as a post-marketing requirement of FDA. Along with the CV management factor, BELVIQ showed significant improvements in some of the pre-defined secondary endpoints such as renal functions, blood sugar levels, blood pressure, lipids etc. Another significant outcome was that the safety profile of this study which further corroborated the already approved label that contains dizziness, urinary tract infection, fatigue and urinary tract infection as the major adverse effects in the study.

“Obesity is a major problem globally and associated with increased risk for heart disease and other serious health conditions such as hypertension, type 2 diabetes and obstructive sleep apnea. The results for BELVIQ from this robust global study provide important information to health care providers and patients, particularly those with cardiovascular and obesity-related complications,” said Lynn Kramer, M.D., Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai.

Alector raises $133M to energize immune cells against neurodegeneration.

Alector, a South San Francisco based Immuno-neurology and immuno-oncology company, recently announced that they had raised $133M in a series E funding round to employ body’s immune system to treat neurodegenerative diseases like Alzheimer’s along with dementia and cancer [6]. The total amount accumulated as fundraiser now adds up to $415 million and has been raised from a varied number of sources such as drug company venture funding arms to GV, the venture capital arm of Alphabet, Google’s parent company.

With its immune system approach to therapies for neurodegeneration, #Alector is riding a tailwind from the promising results from some of the new immunotherapies developed to treat cancer – by @Tansey_Xconomy https://t.co/bqoWXLGbDm

— Xconomy (@Xconomy) July 25, 2018

The basis of Alector’s approach is heavily dependent on the promising results that have been shown for immunotherapy. They are keen to include cancer in their drug target program. For the time being though, their focus is mainly on the role of aging or defective immune system in various disorders of the brain and Alzheimer’s. Their main drug target now aims at treating neurodegenerative diseases. Alector at present has three potential drugs in the form of antibodies that could cross the blood-brain barrier. These are AL001, AL002 and AL003. The latter two are considered as potential treatments for Alzheimer’s disease [7]. These two have been designed to activate the immune cells called microglia, that clean up various cell debris and beta-amyloid aggregates associated with Alzheimer’s. AL002 binds to Trem 2 receptors present on the microglia and facilitates the cleaning by microglia through phagocytosis. AL003 on the other hand functions by blocking Siglce receptor which in its free form would bind to microglia preventing it from performing its usual clean-up function. Both of these have been chosen for co-development with Abbvie under which the two companies will jointly fund the deal and share the profits. Abbvie has already paid $205 million upfront and may make an additional $20 million equity investment. AL001 on the other hand is an antibody that was developed to treat frontotemporal dementia (FTD). FTD is shown to be linked to genetic mutations that hamper the production of progranulin (PGRN). Hence this antibody works by increasing the levels of PGRN. It binds to receptors on microglia and neurons that in turn prevents to degradation of PGRN. If these three Alector’s drugs eventually get approval, they would be administered intravenously through injections to the patients and will have to be taken throughout their lives.

Leo Pharma enters into an agreement to buy Bayer’s dermatology unit.

Very recently Leo Pharma and Bayer announced that the former had entered into an agreement with Bayer to buy the prescription dermatology unit of the latter [8]. The acquisition will include branded topical prescription treatments for fungal skin infections, acne and rosacea including a wide variety of topical steroids that have had an annual turnover of more than 280 million euros in 2017.

LEO Pharma will gain Bayer’s prescription dermatology portfolio – https://t.co/bxSwxGOsiE pic.twitter.com/513lrufGUj

— GMPnews.Net (@GMPnewsNet) August 1, 2018

Bayer is a known global company that has a wide variety of competencies in various fields of healthcare and agriculture. Leo Pharma is known to provide care solutions to patients in more than 130 countries helping them in managing and achieving great skin. Based on this acquisition, Leo Pharma will acquire the global product rights except for Pakistan and Afghanistan. It will be responsible for the marketing and sales in 14 countries, across the world. Even though the transaction includes most of Bayer’s global dermatology unit, its over-the-counter dermatology portfolio of brands such as Bepanthen® and Canesten® will not be a part of this.

“We are very pleased to have found a good partner in LEO Pharma, who has a long history as a leader in scientific advancement and a culture that values discovery and innovation,” said Heiko Schipper, member of Bayer’s Board of Management and President of Consumer Health. “We are very excited about this agreement. With the strong prescription dermatology brands and the new colleagues from Bayer, LEO Pharma advances significantly towards our goal of helping 125 million patients by 2025. We will broaden our treatment range and considerably enhance our size in key markets around the world – underlining our ambition to be a preferred partner in medical dermatology,” said Gitte P. Aabo, President and CEO of LEO Pharma.

About the cover image: Colorized scanning electron micrograph of malaria (Plasmodium yoelii nigeriensis) oocysts ( thick-walled structure in which sporozoan zygotes develop) developing on the midgut wall of the mosquito Anopheles. Technical Details B0007349 Malaria parasites. Wellcome Images available under the following creative commons usage http://creativecommons.org/licenses/by-nc-nd/2.0/uk/. Source: Cell Image Library

References:

[1] https://www.prnewswire.com/news-releases/janssen-announces-us-fda-approval-of-symtuza-dcftaf-the-first-and-only-complete-darunavir-based-single-tablet-regimen-for-the-treatment-of-hiv-1-infection-300682550.html.

[2]https://www.fiercepharma.com/pharma/janssen-wins-fda-nod-for-a-new-once-daily-hiv-med-must-now-find-its-place-market.

[3]https://www.gsk.com/en-gb/media/press-releases/gsk-reports-on-outcome-of-the-fda-advisory-committee-on-mepolizumab-for-the-treatment-of-copd-patients-on-maximum-inhaled-therapy/#splashclose.

[4]https://www.gsk.com/en-gb/media/press-releases/us-fda-approves-krintafel-tafenoquine-for-the-radical-cure-of-p-vivax-malaria/.

[5]http://eisai.mediaroom.com/2018-07-17-Eisai-Inc-Announces-Positive-Topline-Results-from-CAMELLIA-TIMI-61-a-Large-Scale-Cardiovascular-Outcome-Trial-for-the-Anti-Obesity-Agent-BELVIQ-R.

[6] https://www.biocentury.com/bc-extra/financial-news/2018-07-25/alector-raises-133m-series-e.

[7]https://www.xconomy.com/san-francisco/2018/07/25/alector-snags-133m-to-activate-immune-cells-against-neurodegeneration/.

[8]https://www.businesswire.com/news/home/20180731005552/en/LEO-Pharma-Expand-Lead-Medical-Dermatology-Acquisition.

About the Author:

Esha Sehanobish

She is presently a Postdoctoral research fellow at Albert Einstein college of medicine, NY and works on characterization of enzymes that could act as potential therapeutic targets against tuberculosis. She is an enzymologist with a doctoral degree from the University of Central Florida in 2016. She loves using her communication skills to raise awareness about the importance of science in general by using social media. When she is not doing “science”, she loves designing and painting as a way of expressing ones thoughts through graphics and color.

Editor and Blog Design

Abhi Dey

Abhi graduated from the Molecular Biophysics Unit of IISc (Bangalore, India) in 2011. As a Biomedical Scientist, he has worked with all three life-forms in his 13-year research career, viz., particulate, unicellular and multicellular. He is currently an Assistant Scientist at Emory University (Atlanta, GA) studying mechanisms of tumor recurrence in kids with brain tumors. As a postdoctoral fellow, he was the recipient of two Young Investigator Awards from Alex Lemonade Stand Foundation (Philadelphia, PA) and Rockland Immunochemicals. His current research has been funded by Northwestern Mutual Foundation (Milwaukee, WI), CURE Childhood Cancer Foundation (Atlanta, GA) and American Association for Cancer Research (AACR).  When he is not on the bench you will find him spending time with his family or exploring the world through traveling and blogging.

Cover image: Pixabay

The contents of Club SciWri are the copyright of PhD Career Support Group for STEM PhDs {A US Non-Profit 501(c)3}. (PhDCSG is an initiative of the alumni of the Indian Institute of Science, Bangalore. The primary aim of this group is to build a NETWORK among scientists, engineers and entrepreneurs).

This work by Club SciWri is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Disclaimer: This blog is strictly for news and information. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.