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The current edition of Esha Sehanobish’s Medness Plus brings you several #Medness updates beyond Oncology. For the support treatment of #opioid dependence, authorities with #FDA have affirmed another measurement quality of #buprenorphine and #naloxone sublingual film (Cassipa, Teva Pharmaceuticals). In patients with severe #asthma, #mepolizumab significantly reduced clinically significant exacerbations and improved asthma control across all eosinophil levels compared with #benralizumab and #reslizumab. In a major development, a breakthrough #therapy designation for #tezepelumab in patients with #severe #asthma (collaboration of #AstraZeneca #Amgen). In a breakthrough on Alopecia Areata, two studies suggest JAK inhibitors may spur hair regrowth. Also check out the news about a major pharma deal where Novartis sells parts of Sandoz US to Aurobindo Pharma and how a labeling mix-up prompts #Montelukast sodium tablet recall. – Abhi Dey

 

FDA approves the dosage strength for naloxone and buprenorphine sublingual films for maintenance treatment of opioid dependence

In our June edition, we reported that FDA had approved the first generic version of Suboxone sublingual film to treat opioid dependence [1]. As part of a continued effort to combat opioid addiction, FDA recently approved Cassipa (buprenorphine and naloxone) sublingual film for the maintenance treatment for the dependence [2]. Sublingual films are generally applied under the tongue. The new approved dosage of buprenorphine and naloxone is 16 milligrams/4 milligrams. This has been sanctioned in both the generic version and in the brand name in different strengths. Cassipa has been approved to TEVA pharmaceuticals.


A combination of FDA-approved medications such as buprenorphine, naloxone or methadone with behavior therapies and counseling called medication-assisted treatment (MAT) are now used extensively to treat patients with opioid use disorder (OUD). It tends to reduce the opioid withdrawal symptoms along with the desire to use it in the first place without causing the high and low cycles that are commonly associated with opioid abuse or misuse. The use of buprenorphine has shown to decrease the pleasurable effects of opioid making its use less desirable. Data from the Substance Abuse and Mental Health Services Administration showed that patients who receive MAT for the treatment of OUD could reduce the risk of death from all causes to half. Cassipa was approved through 505(b)(2), an abbreviated pathway under the Federal Food, Drug and Cosmetic Act. Any new drug application submitted through this pathway mainly relies on FDA’s previous findings of a similar approved drug that is safe and effective as supported by  published literature. It could then lead to a careful assumption of similar efficacy and safety for the newly proposed drug. The present advancement was based in part on the FDA’s finding of safety and efficacy of Suboxones, a previously approved sublingual film. Pharmacokinetics data further supported the safety and efficacy claim. Cassipa should be used as a part of medication-assisted treatment and should only be used after patient induction and stabilization up to the 16mg of buprenorphine. Adverse effects of the use of the naloxone and buprenorphine sublingual film are hyperhidrosis (excessive sweating), constipation, signs and symptoms of withdrawal, insomnia, headache, nausea, vomiting, oral hypoesthesia (numbness), glossodynia (burning mouth), oral mucosal erythema (inflammation of oral mucous membrane), pain and peripheral edema (accumulation of fluid causing swelling in lower limbs).

Opioid Crisis

From Visually.

 

“There’s an urgent need to ensure access to, and wider use and understanding of, medication-assisted treatment for opioid use disorder. The introduction of new treatment options has the potential to broaden access for patients. For example, the FDA recently described a streamlined approach to drug development for certain medication-assisted treatments that are based on buprenorphine. This streamlined approach can reduce drug development costs, so products may be offered at a lower price to patients and we can broaden access to treatment,” said FDA Commissioner Scott Gottlieb, M.D. He also added, “The FDA is committed to helping those with opioid use disorder transition to lives of sobriety. We’ve taken a number of steps to advance the development of new FDA-approved treatments for opioid dependence and encourage health care professionals to ensure patients are offered an adequate chance to benefit from these therapies. Opioid use disorder should be viewed similarly to any other chronic condition that is treated with medication.”

 

GlaxoSmithKline announces the results of indirect treatment comparisons of benralizumab and reslizumab with Mepolizumab (Nucala) for the treatment of severe eosinophilic asthma

 

The data published in The Journal of Allergy and Clinical Immunology (JACI) led to the recent announcement by GSK that summarized results from an indirect treatment comparing benralizumab and reslizumab with a licensed dose of mepolizumab (Nucala) in patients with severe eosinophilic asthma [3]. It was seen that mepolizumab significantly reduced exacerbations and improved asthma control compared to both benralizumab and reslizumab in patients with similar eosinophil counts.


Severe asthma usually requires a high dose of inhaled corticosteroids (ICS) and a second controller such as systemic corticosteroids to prevent the disease from becoming “uncontrolled”. Sometimes it is also characterized by the long-term use of oral corticosteroids. A category of such severe asthma is caused by the overproduction of eosinophils thus causing inflammation of lungs. Interleukin 5 (IL-5) promotes the eosinophil growth and survival thus signaling the movement of eosinophil from bone marrow to the lungs. Nucala (mepolizumab) is the first-in-class monoclonal antibody that was first approved in 2015 for treating severe eosinophilic asthma. It targets IL-5 thus preventing the binding to its receptor on the surface of eosinophils. Due to the inhibition of IL-5 binding, there is a reduction in the level of blood eosinophils. Hence it was developed for the treatment of diseases that are driven by inflammations caused due to eosinophils. Currently, in Europe, it is the only anti IL5 therapy that is approved and available for pediatric treatment of eosinophilic asthma from ages 6-17. It is also under investigation as a potential cure for nasal polyposis, COPD and hypereosinophilic syndrome. The data was obtained from 11 different studies identified through Cochrane review process of anti-IL5 pathway directed therapies and additional literature. The studies were randomized controlled trials in patients ≥12 years of age with severe eosinophilic asthma as per predefined definition. Mepolizumab showed a clinically significant reduction in exacerbations by 34%-45% when compared to benralizumab across subgroups and showed a clinically significant reduction in exacerbations by 45% versus reslizumab. It also showed a significant improvement in asthma control as assessed by the Asthma Control Questionnaire (ACQ) score. There was no significant difference in lung function measured by the change from the baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1). Endpoints of the study involved the annualized rate of clinically significant exacerbations, change from the baseline in FEV1 and the ACQ score.

ASTHMA Super specialist

From Visually.

“This analysis was undertaken to try to dissect an important clinical question: how can the various anti-IL5 approaches be evaluated? As a consequence, this study helps improve our understanding of the relative efficacy of the three available anti-IL5 pathway directed treatments for patients with severe eosinophilic asthma when grouped by patients’ blood eosinophil counts, which are known to influence treatment effect. Only licensed doses used in clinical practice were included and patients were matched according to blood eosinophil counts and asthma control scores. This approach ensured a robust comparison, which will help inform doctors when making clinical decisions about treating their patients,” said Dr William Busse, Professor of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Department at the University of Wisconsin Medical School in Madison, Wisconsin.

FDA announce the voluntary recall of Montelukast tablets by Camber Pharmaceuticals due to incorrect drugs in the bottles

In an urgent warning issued by FDA, it announced a voluntary recall of one lot of Montelukast Sodium tablets, lot number MON17384 with an expiration date of 12/31/2019 by Camber Pharmaceuticals, Inc., Piscataway, NJ. The mix up resulted in incorrect drugs in sealed bottles. As per the label, this lot of bottles were supposed to contain 30, 10mg Montelukast sodium tablets but were found to contain 90 Losartan Potassium tablets, 50mg [4]. This recall has nothing to do with the recent recall of valsartan that was triggered due to the impurity of N-nitrosodimethylamine (NDMA).


The error in packaging is a major safety issue since losartan tablets when not prescribed, can cause elevated potassium levels, renal dysfunction and low blood pressure. It is especially dangerous for pregnant women taking asthma and allergy medications because losartan which is usually needed to treat high blood pressure, could damage or even the kill fetus. Hence patients who have this recalled product are advised to inform their healthcare provider and pharmacists immediately. Losartan is either used alone or in combination with other medications and along with high blood pressure it is also used to decrease the risk of stroke with people with blood pressure issues and a heart condition called ventricular hypertrophy. This condition involves enlargement of the walls of the left side of the heart. On the other hand, Montelukast is used to prevent difficulty in breathing, wheezing, chest tightness and coughing caused by asthma. The mode of action of Montelukast is that it blocks the action of substances in the body that causes the symptoms of asthma and allergic rhinitis. It belongs to a class of leukotriene receptor antagonists (LTRAs). The drug is also used to prevent bronchospasm during exercise and to treat symptoms caused by seasonal and potential rhinitis. Considering the completely different functions that the medicines perform, a mix up in the same could lead to severe adverse reactions in patients.

https://www.youtube.com/watch?v=aoxRV3yygl0

“We want to ensure that patients who take montelukast are aware of this recall due to the serious risks associated with taking losartan in its place,” said Donald D. Ashley J.D., director of the office of compliance in the FDA’s center for drug evaluation and research. “Patients who take prescription drugs expect and deserve to have the medication their doctor prescribed.”

 

Tezepelumab by AstraZeneca and Amgen, granted Breakthrough Therapy designation by FDA

AstraZeneca and its partner Amgen recently announced that FDA had granted a Breakthrough Therapy designation to Tezepelumab for patients with severe asthma without an eosinophilic influence who are being treated with inhaled corticosteroids/ long-acting β2 agonists with or without oral corticosteroids and additional asthma controllers [5]. A Breakthrough Therapy designation is conferred to hasten the development and reviewing process of medicines that are supposed to treat serious diseased conditions and are based on promising clinical results that show a clinical significance in the endpoint compared to the already available medications.


As described above, severe asthma may require the use of chronic oral corticosteroids (OCS) as it could be difficult to control using the usual asthma controllers. For extremely severe cases of asthma patients, life-threatening effects on lung functions could be experienced. Various factors are involved in the pathogenesis of asthma. The T2 inflammation driven one is usually characterized by increased levels of T2 inflammatory biomarkers such as serum IgE, blood eosinophils and fractional exhaled nitric oxide. This form includes the eosinophilic phenotype which is present in over two-thirds of patients with severe asthma. Tezepelumab is known to block an epithelial cytokine, TSLP, that is critical in the initiation and persistence of airway inflammation. The blocking of TSLP could prevent the release of pro-inflammatory cytokines thus controlling asthma exacerbations with improved asthma control. The designation was conferred based on the results of the Phase IIb PATHWAY trial. The data was published in the New England Journal of Medicine. The trial evaluated the efficacy and safety of 3 doses of tezepelumab as an add-on therapy for patients with asthma exacerbations and uncontrolled asthma, who were already receiving treatment. Tezepelumab blocks the thymic stromal lymphopoietin (TSLP), an upstream modulator of multiple inflammatory pathways. From the data, it is evident that there is a clinically significant reduction in the annual asthma exacerbation rate compared to the placebo data in a population of patients with severe asthma including those with Type 2 biomarker status. There is a 62%, 71% and 66% reduction in the rates in those receiving 70mg or 210mg every four weeks or 280mg every two weeks compared to the placebo. The adverse effects of the treatment included nasopharyngitis, headaches and bronchitis which were usually asthma-related.

“Tezepelumab is exciting because it has the potential to treat a broad population of severe asthma patients, including those ineligible for currently-approved biologic therapies. The Breakthrough Therapy Designation will help us bring tezepelumab to patients as quickly as possible,” said Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca.

 

Pfizer receives Breakthrough Therapy designation from FDA for the treatment of patients with Alopecia Areata

Pfizer Inc. announced that its investigational oral Janus kinase3 (JAK3) inhibitor PF-06651600 recently received the designation of Breakthrough Therapy by FDA. It will be targeted to treat patients with alopecia areata, a chronic autoimmune disease that causes loss of hair on the face, body or scalp [6].


FDA’s decision to grant a Breakthrough Therapy designation to the JAK3 inhibitor was supported by positive results from a Phase 2 study. The data of this study is scheduled to be presented during the late-breaking news sessions at the 27th European Academy of Dermatology and Venerology (EADV) Congress in Paris on 15th September 2018. The autoimmune disease Alopecia areata is characterized by loss of hair on the body, face and on the scalp. These manifestations are a result of the attack of immune cells on healthy hair follicles causing the hair loss. It often starts off as smooth round patches. The average age of adults with this disease ranges between 25 and 35. Sometimes children and adolescents can also be affected by this disease. It is seen uniformly in both the genders and often the patients experience poor health-related issues with a decrease in the quality of life standards. This could lead to serious psychological disorders with high levels of anxiety and depression. Currently, there are no known FDA approved treatments for the disease which is prevalent around the world. The JAK pathways are essential in signaling involving more than 50 cytokines and growth factors. JAK inhibition is now considered as a potential target for treatment options for immune-mediated diseased conditions. The JAK3 inhibitor PF-06651600 is an oral small molecule that is also under investigation for its potential application in the treatment of rheumatoid arthritis, Crohn’s disease and Ulcerative colitis. Pfizer has been focusing extensively on establishing kinase inhibitor specific therapies. There are a few other investigational programs in the pipeline that will soon help them achieve their goal. There is PF-04965842, a selective JAK1 inhibitor in the Phase 3 clinical trial for the treatment of atopic dermatitis and has already received an FDA designation of Breakthrough Therapy. Amongst a few others, PF-06700841 is a tyrosine kinase 2 inhibitor that is under investigation for the treatment of Crohn’s disease, psoriasis, ulcerative colitis and alopecia areata.

Hair Loss Explained

From Visually.

“We are encouraged by this Breakthrough Therapy designation as it underscores the potential of our JAK3 inhibitor to address a critical unmet need,” said Michael Corbo, Chief Development Officer, Inflammation and Immunology, Pfizer Global Product Development. “We are continuing to work closely with the FDA on the development process with the goal of bringing this potential new treatment to patients living with alopecia areata as soon as possible.”

 

Novartis announces its plan to sell the Sandoz US dermatology business and generic US oral solids portfolio to Aurobindo Pharma, USA

 

Novartis recently announced that they are on the verge of selling selected portions of Sandoz US portfolio to Aurobindo Pharma USA Inc. for 0.9 billion USD and 0.1 billion USD for potential earn-outs. The sections of the company that will be sold included the Sandoz US dermatology business and generic US oral solids portfolio [7]. The transaction will be carried out keeping in mind the strategy of Sandoz that focusses mainly on complex generic, value-added medicines and biosimilars to obtain a sustainable growth in the US over a long period. The transaction is estimated to reach completion during 2019.


The portfolios that are up for sale to Aurobindo include approximately 300 products along with the others that are at a developmental stage. The deal includes the dermatology development center and the Sandoz US generic and branded dermatology business. Aurobindo will acquire the manufacturing facilities in Hicksville and Melville, New York and the one at Wilson, North Carolina. As per the agreement, around 750 employees in Wilson, Hicksville, Melville and Princeton NJ along with the field representatives for the PharmaDerm branded dermatology business are expected to transfer to Aurobindo upon closing. Sandoz US portfolio will continue to be substantial following the transaction. It will include biosimilars, complex generics such as injectables respiratory and ophthalmics.

“Sharpening our portfolio focus in the US allows us to devote more time and resources toward our strategy of bringing complex generics, value-added medicines and biosimilars to patients in the US, creating higher value and opening up access to important medicines where alternatives are truly needed,” says Richard Francis, CEO Sandoz and Member of the Novartis Executive Committee. “Through this transaction, we are refocusing our business but also striving to ensure continuity of supply of important long-used generic medicines for patients and customers in the US.”

 

Reference:

[1] https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm610807.htm.

[2] https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm619864.htm.

[3] https://www.gsk.com/en-gb/media/press-releases/gsk-announces-results-of-indirect-treatment-comparisons-of-nucala-to-benralizumab-and-reslizumab-for-severe-eosinophilic-asthma/.

[4] https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm619174.htm.

[5] https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2018/tezepelumab-granted-breakthrough-therapy-designation-by-us-fda-07092018.html.

[6]https://www.pfizer.com/news/press-release/press-release-detail/pfizer_receives_breakthrough_therapy_designation_from_fda_for_pf_06651600_an_oral_jak3_i nhibitor_for_the_treatment_of_patients_with_alopecia_areata.

[7] http://www.worldpharmanews.com/novartis/4531-novartis-to-divest-the-sandoz-us-dermatology-business-and-generic-us-oral-solids-portfolio-to-aurobindo.

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: (Cell Image Library)Scanning electron micrograph of human hair. The image illustrates the size and distensibility of human hair. Image collected on FEI instrument Nova NanoSEM Family with a magnification of 400x, and a Voltage of 7kv. A SE Spot detector with a 3 nA at a working Distance of 3 mm was used to collect the image..

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).

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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. 

The authors and editors for Medness Plus declare no financial benefits or remuneration from the sponsors. The sponsorships support the non-profit organization, PhD Career Support Group (PhD CSG). The research conducted for this article by authors and editors is a voluntary effort to popularize science for the public on behalf of PhD CSG.

 

 

 

 

 

 

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The contents of Club SciWri are the copyright of Ph.D. 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.

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