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FDA approves the use of the first generic version of Sabril to treat seizures in patients with epilepsy


FDA recently announced the approval of the first generic version of Sabril (vigabatrin) for the treatment of seizures, as an adjunct therapy, in pediatric and adult patients [1]. These include patients 10 years and older, specifically those who do not respond adequately to alternative, refractory treatments. The drug was found to be the most effective in the treatment of complex partial seizures also referred to as focal seizures. The approval was given to Teva Pharmaceuticals, USA.

The focal seizures are usually complex partial seizures that originates from a part of the brain and can last for 30-90 secs. It is often followed by a span of confusion, fatigue, disorientation thus overall affecting consciousness. The labeling of the generic variety of the 500 mg Sabril tablets include boxed warnings of permanent vision loss. These tablets are a part of a single shared system Risk Evaluation and Mitigation Strategy (REMS) program containing vigabatrin to ensure the safe and efficient use of the product. When a drug maker seeks approval for a generic drug having a REMS associated with it, it is essential that a single shared-system REMS program is developed. The only exception is if the FDA waives the requirement of such a system. There is a rigorous approval standard for such generic drugs to ensure that the products are as effective and safe as their brand counterparts. Therefore, the FDA has begun publishing a series of inquiries as required by the generic drug developers who seek the assistance of FDA in acquiring samples from the brand companies. It is to be noted that the branding companies limit the distribution program. According to the FDA, there should be a path forward for generic drug development, even under such programs. To provide transparency and value to the process of generic drug development, FDA released lists of off-patent, off-exclusivity branded drugs without generics in 2017. At present, along with brand names, the FDA also inspects manufacturing and packaging facilities for generic drugs to ensure consistent production of high-quality products. Some of the more common side effects documented with the use of vigabatrin tablets includes upper respiratory tract infection, fatigue, involuntary eye movements, tremor, dizziness, blurred vision, weight gain, memory impairment, abnormal coordination, joint pain and diplopia or double vision. Suicidal thoughts or actions and permanent loss of vision are some of the serious side effects associated with the use of vigabatrin tablets.

Epilepsy Etiquette Guide

From Visually.

 

“Prioritizing the approval of generic drugs to compete with medicines that face little or no competition is a key part of our efforts to support access and reduce drug costs to patients. The availability of high-quality generic alternatives of critically important medicines, once the period of patent protection or exclusivity has ended on the brand drug, helps advance access and saves consumers billions of dollars each year. We know there has been past interest in developing a generic alternative to this product. Earlier this year, we also highlighted this drug, along with many others, on a list of off-patent, off-exclusivity branded drugs without approved generics, to clarify that there were no patents or exclusivities that should impede its approval. Today’s action demonstrates that there is an open pathway to approving products like this one. We’re especially focused on new policies aimed at making the generic review process more predictable, efficient and lower cost so we can entice more generic firms to enter this space and help facilitate more generic drug launches after generic approvals. We know it’s not enough just to approve a record number of generic medicines. We also want to see firms launch these products so that patients can benefit from their availability, and we intend to take steps to advance these goals,” said FDA Commissioner Scott Gottlieb, M.D.

 

FDA approves the marketing of a new test to help in the diagnosis of a sexually-transmitted infection


FDA recently approved the marketing of a test to diagnose the presence of a sexually-transmitted infection (STI) caused by Mycoplasma genitalium (M. gen.) [2]. This bacterium causes cervicitis (inflammation of the cervix) in women, non-gonococcal urethritis (inflammation of the urethra) in men and pelvic inflammatory disease (infection of the reproductive organs) in women. The approved test is the first of its kind authorized by the FDA, to test for the presence of the bacterium M. genitalium. The Aptima Mycoplasma Genitalium Assay was approved by FDA to Hologic Inc.

The Aptima Mycoplasma Genitalium Assay, is a nucleic acid amplification test that detects the presence of M. gen bacterium in urine, urethral, endocervical, penile meatal or vaginal swab samples collected by healthcare professionals. Based on the data obtained from the CDC, the bacterium is responsible for approximately 10 to 30 percent of cervicitis cases in women and 15 to 30 percent of persistent urethritis cases in men in the US. M. gen. is a difficult bacterium to combat since it is slow-growing and difficult to be identified with traditional clinical methods. The approval was based on data from a clinical study that involved 11,774 samples. The test was able to correctly identify the bacteria in 90 percent of vaginal, male urine, urethral and penile samples. 77.8 percent was its success rate in the case of female urine samples 81.5 percent in cases of female endocervical samples. The study also showed that the test was able to correctly identify samples that were not infected by the bacterium, approximately 97.8 to 99.6 percent of the time. Vaginal swabs were usually preferred over the other available sample types for better clinical performances. The De Novo premarket pathway was used to review the Aptima Mycoplasma test. It is a regulatory pathway used for low-to-moderate-risk devices of a new type. It is part of an effort from the FDA to have better control on such tests so that they can exhibit accuracy and reliability. A new regulatory classification has thus been created so that subsequent similar devices go through the FDA’s 510(k) premarket process, by which the devices can obtain marketing authorization by depicting similarity with a previous device.

STDs in America

From Visually.

 

“Patients with unidentified urogenital infections are typically treated with antibiotics, some of which may not be effective against M. gen. In the past, it has been hard to diagnose this organism. By being able to detect it more reliably, doctors may be able to more carefully tailor treatment and use medicines most likely to be effective. In cases where M. gen. is detected, doctors can consider forgoing use of antibiotics that are known to be ineffective against M. gen. and choose a treatment more likely to be appropriate. Having accurate and reliable tests to identify the specific bacteria that’s causing an infection can assist doctors in choosing the right treatment for the right infection, which can reduce overuse of antibiotics and help in the fight against antimicrobial resistance,” said FDA Commissioner Scott Gottlieb, M.D.

 

FDA places a clinical hold on the Investigational New Drug Application on MRT5201 for the treatment of ornithine transcarbamylase deficiency


Translate Bio, a clinical stage messenger RNA (mRNA) therapeutics company recently announced that FDA has placed a hold on the Investigational New Drug Application on MRT5201, a drug used for the treatment of Ornithine Transcarbamylase (OTC) deficiency [3]. After careful review, FDA has laid out further clinical and non-clinical questions. The IND was submitted in December 2018 and was supposed to to carry out the Phase 1/2 clinical trial with OTC deficiency. A clinical hold has been placed on this until satisfactory answers are obtained for FDA’s specific questions regarding the trial. The company has agreed to work with the organization in the near future and resolve all the queries as fast as possible. Following this announcement, there was a dip in Translate Bio’s stock price of more than 9.3 percent to $5.01 per share [4].

MRT5201 was granted orphan drug designation in the U.S and EU for the treatment of OTC deficiency. It was designed to treat patients with the deficiency by intravenous delivery of mRNA encoding fully functional OTC enzyme to the liver to allow the hepatocytes to generate the normal OTC enzyme. In case of deficiency of OTC enzyme, there is a buildup of ammonia which usually acts as a neurotoxin. The treatment includes removal of the ammonia and other nitrogen products, which could be induced by various dietary restrictions and in some cases liver transplant. Translate Bio is focused on developing medicines for the treatment of diseases caused by gene and protein dysfunction. It is a clinical-stage mRNA therapeutics company. Its MRT platform, designs various candidates that deliver mRNA carrying instruction to generate transmembrane, secreted and intracellular protein for therapeutic benefits. The main reason why the MRT platform has been created is to produce delivery systems to treat diseases caused by insufficient protein production and those where production of proteins can alter diseases affecting eye, liver, lungs and the CNS. The company believes that the platform could further be used to treat infectious diseases and might be useful in oncology. The two most important projects of Translate Bio, at present, is the development of treatment for OTC deficiency and for cystic fibrosis.

 

FDA grants a Breakthrough Therapy designation to Novartis’s investigational therapy, crizanlizumab (SEG101)


FDA granted a Breakthrough Therapy designation to crizanlizumab (SEG101), a product of Novartis, to prevent vaso-occlusive crises (VOCs) in patients with all genotypes with sickle cell disease [5]. VOCs are caused when multiple blood cells adhere to each other and also to blood-vessels, thus causing blockages. As a result, VOCs can be very unpredictable and may lead to painful, chronic and acute complications. The treatment for such conditions would be directed towards reducing the stickiness of the blood cells to each other and to other blood vessels.

The Basics About Pediatric Sickle Cell Disease

From Visually.

 

Sickle cell disease is a blood disorder, genetic in nature, that affects the shape of the red blood cells. Due to this the cells and blood vessels may become stickier. The adhesion of these cells and vessels usually leads to blockage which obstructs the flow of oxygen and blood thus leading to damage of the blood vessels and organs. Vaso-ocular crises arises due to such painful events and complications. Along with an annual cost of $30000 for adults with sickle cell disease, the lifetime health cost for a patient could go up to $1 million. Its treatment is thus counted as one of the more expensive ones. Crizanlizumab (SEG101) is a humanized anti-p-selectin monoclonal antibody that binds to P-selectin molecule on the surface of platelets and endothelium in blood vessels. This inhibits the interaction between platelets, blood cells, endothelial cells, sickled and normal red blood cells creating a blockade and prevents the binding to P-selectin. Since P-selectin is one of the major factors in the vaso-occlusive process, affecting this molecule will help in the prevention of VOCs. Further studies will have to be conducted to determine the mechanism for crizanlizumab to treat VOCs in patients. The Breakthrough Therapy designation was conferred by FDA based on positive results of the Phase II SUSTAIN trial. In this the P-selectin inhibitor crizanlizumab was compared with placebo in patients with the sickle cell disease. There was a reduction in the median annual rate of VOCs for crizanlizumab leading to health care visits by 45.3% compared to placebo in patients with or without hydroxyurea therapy. The study also showed that there was an increase in the percentage of patients who did not experience any VOCs vs placebo (35.8% vs 16.9%) during treatment. A similar incidence of treatment-related adverse effects and serious adverse effects were observed for crizanlizumab (5 mg/kg) and placebo. There was a low incidence of discontinuation due to adverse effects. Some of the adverse effects that were observed included vomiting diarrhea, pruritus, arthralgia and chest pain. No apparent increase in infections with the antibody treatment was observed. Usually, a Breakthrough Therapy designation is given to those that are predicted to treat life-threatening or serious conditions and are expected to be better than the existing therapies based on the preliminary clinical data.

“Painful sickle cell crises matter because they can disrupt patients’ lives, and often require hospital visits and medical attention,” said Samit Hirawat, MD, Head, Novartis Oncology Global Drug Development. “We look forward to working closely with the FDA over the coming months toward making crizanlizumab, a therapy that has the potential to prevent sickle cell pain crises, available in the US as soon as possible.”

 

FDA Advisory committee give positive vote for the approval for EVENITYTM (romosozumab)


Union Chimique Belge (UCB) and Amgen, recently announced that FDA’s Bone Reproductive and Urologic Drugs Advisory Committee (BRUDAC) has strongly supported the approval of EVENITYTM for women with osteoporosis [6]. The decision has been made based on a pivotal Phase 3 study in which the safety and efficacy was taken into consideration for women with osteoporosis who are highly disposed to fractures. The committee has requested for a post-marketing follow-up. At present eighteen of the nineteen members of the committee have voted yes.

Know Your Risks of Osteoporosis

From Visually.

 

The incidence of osteoporosis globally, in women, is usually pretty high thus increasing their chances of fracture. Statistics show that one in three women and one on five men over the age of 50 is likely to undergo fracture due to osteoporosis, with age being a critical factor in the process. Based on data available it has been observed that the treatment after such an event is not adequate and a lot of patients remain undiagnosed and untreated following a fracture episode. This could in the future, lead to debilitating effects in the ageing population. EVENITY (romosozumab) is an investigational bone-forming monoclonal antibody. EVENITY inhibits the functioning of sclerostin, thus inducing quick bone formation and reducing bone resorption. 19 clinical studies and around 14000 patients were involved in the EVENITY development program. It was also studied in a global Phase 3 program for its efficiency in reducing the risk of fractures. EVENITY is a collaborative effort of Amgen and UCB. A couple of trials were carried out under the EVENITY development program. FRAME (Fracture study in postmenopausal women with osteoporosis) was a double-blind, randomized, placebo-controlled study. 7180 postmenopausal women at a risk for fracture, were enrolled into program. The effectiveness of 210mg administration (monthly) of EVENITY was compared to the effects of placebo in reducing the risk of vertebral fractures through a period of 12 months. Another aspect in which the effectiveness of EVENITY treatment for 12 months was studied followed by denosumab for 12 months and was compared to placebo followed by denosumab in reducing the risk of the fractures for a period of 24 months. ARCH (Active controlled fracture study in postmenopausal women with osteoporosis at high risk fracture) was the second trial in the development program. It was a randomized, double-blind, alendronate-controlled study of EVENITY in 4093 postmenopausal women with a history and a greater risk for fracture. The study included 210 mg monthly administration of EVENITY followed by 70 mg of at least 12 months of alendronate treatment and was compared to the alendronate treatment alone. The aim of the study was to determine the efficiency of the drug in reducing clinical fracture (clinical vertebral fracture and non-vertebral fracture) and a new one. A third clinical trial was named STRUCTURE (Study evaluating effect of romosozumab compared with teriparatide in postmenopausal women with osteoporosis at high risk for fracture previously treated with bisphosphonate therapy). It was a Phase 3, randomized, multicenter, international, open-label, teriparatide-controlled study. The aim of the study was to assess the tolerability, safety and efficacy of EVENITY in postmenopausal women with osteoporosis. 436 postmenopausal women with an average age of 72 years and a history and high risk of bone fracture, were the subjects of the treatment. They were treated with bisphosphonate therapy for a minimum of three years before screening along with 70 mg weekly of equivalent treatment with alendronate during the year prior to screening. Even though FDA is not bound to accept the Advisory Committee’s recommendation, it is a general practice to consider it while making the final decisions.

“We are pleased with the Committee’s recommendation to approve EVENITY for the treatment of postmenopausal women with osteoporosis at high risk for fracture,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen. “A fracture due to osteoporosis can be devastating to the lives of patients. After an osteoporotic fracture, a woman is five times more likely to suffer another fracture within the first year, and her risk remains elevated over time if untreated.1 Despite available therapies, these women who are at high risk for fracture could benefit from an additional treatment option that has the potential to both build new bone and slow existing bone loss. We are committed to working with the FDA to help make EVENITY available to appropriate patients.”

 

 

GlaxoSmithKline and Medicine for Malaria Venture announces positive results from two phase III study for the treatment of Plasmodium vivax


Medicine for Malaria Venture (MMV) and GSK recently announced the positive results from the Phase III study of single-dose tafenoquine for the prevention of relapse of Plasmodium vivax malaria [7]. The study was published in The New England Journal of Medicine. Two comprehensive global studies supported the approval of a single-dose tafenoquine by FDA in July 2018 and by the Australian Therapeutic Goods Administration in September 2018, for the cure of the P. vivax malaria.

The parasite, Plasmodium vivax, is an evolved and complicated organism with a lifespan in both mosquitoes and humans. The parasite is capable of infecting the blood upon an infected mosquito bite and can thus cause malarial episodes. Relapses of the P. vivax malaria is very common because the parasite can survive in a dormant form (hypnozoite) in the liver. Thus, a person infected by the P. vivax parasite can undergo multiple episodes of malaria even in the absence of a fresh mosquito bite. The reason why the parasite is dangerous is that the dormant form is almost untreatable by most of the available antimalarial treatments, known to be effective against the active varieties. Some of the symptoms of the infection include fever, chills, headache, muscle pain and in some cases could even be life-threatening. It has a widespread economic impact mainly in parts of South and South-East Asia, parts of Africa and Latin America thus accounting for 7.5 million in clinical infections every year. Till very recently, the 8-aminoquinoline, primaquine, was the only approved medicine that was effective against the dormant liver stage. But the drawback of the 14-day treatment is that it has poor compliance, thus leading to a reduction in the efficiency. The positive data which was published in The New England Journal of Medicine was obtained from two major clinical trials. The first one was DETECTIVE/TAF112582 (Dose and efficacy trial evaluating Chloroquine and Tafenoquine in Vivax elimination). It was a double-blind, phase III, double-dummy study whose aim was to determine the tolerability, efficacy and safety of tafenoquine in 522 patients with the P vivax malaria from places like Ethiopia, Peru etc. Since it was a randomized trial, patients received either a 1-day dose of 300 mg of tafenoquine, a 14-day course of 15 mg primaquine or placebo, with all patients also receiving a 3-day course of chloroquine. The data from the study was analyzed and it was found that there was a significantly high proportion of the patients in the tafenoquine group that remained relapse-free for over a 6-month period, when compared to the placebo group. A significantly higher proportion of patients of the primaquine group were found to be relapse-free as well for a period of 6 months. The adverse effects reported from the study were similar to the known safety profile of tafenoquine. The second study was called GATHER/TAF116564 (Global Assessment of tafenoquine hemolytic risk). It was a double-dummy, double-blind Phase III study aimed at determining the safety of 300 mg of tafenoquine on the levels of hemoglobin, when compared to a 15 mg, 14-day course of primaquine and with all the patients receiving a standard 3-day course of chloroquine. 251 P. vivax malaria patients from Countries like Peru, Brazil, etc. were involved in the study. From the data it was determined that the incidence of decline in hemoglobin was low and was comparable in both the groups. The frequency of adverse effects for the tafenoquine and the primaquine group was similar and was 72% a 75% respectively.

Born in this world #6: fourth year

by oliviermarie.

From Visually.

 

“Without treatment to stop the relapse of P. vivax, infected patients live with the constant threat of malarial symptoms returning without warning. MMV and GSK, long-standing partners in the fight against malaria, developed tafenoquine to help put a stop to the relapse. We are delighted to see the results of the phase III studies published in the NEJM. These positive results demonstrate the efficacy and safety of tafenoquine in an unprecedented single-dose for relapsing malaria, potentially offering countries a new tool as they strive towards malaria elimination,” said Dr. David Reddy, Chief Executive Officer of MMV. Dr. Hal Barron, Chief Scientific Officer and President of Research and Development, GSK, said: “Treating Plasmodium vivax malaria is particularly challenging because the parasite has the ability to lie dormant in the liver resulting in relapses. Poor compliance to primaquine treatment in real-world settings can lead to higher relapse rates than those seen in the controlled setting of clinical trials, so a single-dose treatment with tafenoquine is an attractive proposition. We are pleased to have the results of these pivotal studies published today and look forward to progressing further regulatory filings of tafenoquine in P. vivax endemic countries.”

 

Sandoz, Inc announces the launch of SYMJEPITM in the US


The Sandoz Inc., a global leader in biosimilars and generic pharmaceuticals and a division of Novartis recently announced the commercial availability of SYMJEPITM (epinephrine) in the US market [8]. It will be available as a 0.3 mg injection for the emergency treatment of allergic reactions (type 1), that includes anaphylaxis. Based on claims by Sandoz, the injection will be affordable, single-dose, pre-filled alternative to epinephrine auto-injectors.

The 0.3 mg injection will be used for the treatment of allergic reactions such as anaphylaxis to the bites and stings of an insect, food, drugs, allergen immunotherapy and other forms of allergens. It can also be used for the treatment of exercise-induced anaphylaxis. The injection is expected to be administered immediately in patients who weigh 66 pounds or more and are considered to be prone to anaphylaxis and those with a history of the same. SYMJEPI will first be launched in an institutional setting, where Sandoz has significant experience and knowledge and will later be launched into the retail market.

Epipen Just the Facts

From Visually.

 

“The SYMJEPI device is small in size and fits into the palm of your hand, with the goal of a simple-to-use application and intuitive, user-friendly design,” said Carol Lynch, President of Sandoz Inc. “At Sandoz, we strive to reimagine medicine to offer the best care we can in all we do, and having heard from patients, caregivers and healthcare professionals about their eagerness for a new product, we are proud to be a part of the solution to a critical need in the US.”

 

References:

  1. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm629569.htm.
  2. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm629746.htm.
  3. https://investors.translate.bio/news-releases/news-release-details/translate-bio-announces-fda-clinical-hold-investigational-new.
  4. https://xconomy.com/boston/2019/01/22/fda-places-clinical-hold-on-translate-bios-mrna-drug-study/?mc_cid=211ec93ff5&mc_eid=7420647896.
  5. https://www.novartis.com/news/media-releases/novartis-investigational-therapy-crizanlizumab-seg101-receives-fda-breakthrough-therapy-designation-prevention-vaso-occlusive-crises-sickle-cell-disease.
  6. https://www.amgen.com/media/news-releases/2019/01/amgen-and-ucb-receive-positive-vote-from-fda-advisory-committee-in-favor-of-approval-for-evenity-romosozumab/.
  7. https://www.gsk.com/en-gb/media/press-releases/two-positive-phase-iii-studies-of-tafenoquine-for-the-radical-cure-of-plasmodium-vivax-malaria-published-in-the-new-england-journal-of-medicine/.
  8. https://www.us.sandoz.com/news/media-releases/sandoz-inc-launches-symjepi-epinephrine-us.

 

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) Description: “Micrograph of developing bone (ossification) in a bird. The image was collected at 200x using brightfield illumination. Honorable Mention, 2011 Olympus BioScapes Digital Imaging Competition®.”

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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).

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