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FDA approves the first generic Advair Diskus for the treatment of patients with asthma.


FDA recently approved the twice-daily use of the first generic Advair Diskus (fluticasone propionate and salmeterol inhalation powder for the treatment of patients with asthma. Patients four years and above will be benefitted by the treatment [1]. It is expected to be useful in the treatment of chronic obstructive pulmonary disease (COPD) targeting the airflow obstruction and decreasing exacerbations in these patients. The following generic inhalers of Mylan has been granted approval by the FDA, fluticasone propionate 100 mcg (microgram)/ salmeterol 50 mcg, fluticasone propionate 250 mcg/ salmeterol 50 mcg and fluticasone propionate 500 mcg/ salmeterol 50 mcg. The usual side effects for the treatment of asthma involving fluticasone propionate and salmeterol inhalation powder involves, oral candidiasis, swelling in the back of the throat, cough, bronchitis, nausea, headaches, vomiting and dysphonia or trouble in speaking. The common side effects from the treatment of COPD include pneumonia, musculoskeletal pain, viral infections, throat irritations and dysphonia.

Inhalers are an amalgamation of a device and a drug and are referred to as combination products. They are usually prescribed for patients with asthma. Asthma is a chronic lung disease that causes inflammation in the airway and thus constricts it. The common symptoms include shortness of breath, coughing, periods of wheezing and coughing. It affects people of all ages and based on the data from the National Health, Lung and Blood Institute, more than 26 million people in the United States are known to have asthma. 7 million children alone are affected by this chronic condition. COPD is considered to be a progressive form of lung disease. Its symptoms include shortness of breath, wheezing, large amounts of mucus production and chest tightness. The generic combination development is very challenging when compared to the oral intake of tablets. FDA has recognized this challenge and has developed rules and regulations to help companies cope with this problem. Based on GDUFA II, various companies can now directly interact with the FDA and support the development of such generic complex products as a part of pre-ANDA program. Various FDA sanctioned documents are also available that provide the steps that the FDA recommends companies to follow to submit approvable and complete applications for their target drug product. Back in 2013, FDA issued a draft with specific guidance for proposed generic drug products referencing Advair Diskus which also enlisted formulations, device considerations and bioequivalence recommendations. FDA also inspects the manufacturing and packaging facilities to endure that the companies are capable for generating quality products, consistently.

When Allergies Attack: Asthma and Allergies in America

by tastyplacement.

From Visually.

 

“Today’s approval of the first generic drug product for one of the most commonly prescribed asthma and COPD inhalers in the U.S. is part of our longstanding commitment to advance access to lower cost, high quality generic alternatives,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research. “People living with asthma and COPD know too well the critical importance of having access to the treatment they need to feel better. Today’s approval will bring more competition to the market which will ultimately benefit the patients who rely on this drug.”

 

FDA issues a warning related to recall of home-use test strips used with devices to monitor blood thinner warfarin.


FDA recently issued a warning for patients and doctors who use in-office or at-home medical devices to monitor the level of warfarin, a blood thinner [2]. The warning has been generated in context to certain test strips used with these devices as they have been found to produce inaccurate results and no dosage adjustments should be made based on these test results. The recall was made last month on behalf of Terrific Care/Medex Supply LLC for certain Roche Diagnostics test strip lots used with CoaguCheck test meter devices. FDA has placed this under Class I recall which is the most serious type of recall as use of these devices may lead to serious injuries and even death. This warning is related to the recall in November 2018 Roche Diagnostics Recall, the manufacturer of CoaguChek meters and test strips. These test strips are used with CoaguChek XS Pro, CoaguChek XS plus, CoaguChek professional, CoaguChek XS PST and CoaguChek Vantus test meter devices. Healthcare providers and patients using these CoaguChek meters have been advised to stop using test strips from Terriffic Care/Medex Supply and use an alternative test method.

A large number of people are dependent on warfarin as blood thinners to prevent and treat blood clot. They are usually prescribed for patients with certain medical device implants such as artificial heart valves, those with blood clots in the lungs or legs and those with irregular heartbeats. Such patients when on appropriate dosage also need constant monitoring, to keep a track of the time required by the blood to clot. A blood test is done for these reasons and the International Normalized Ratio (INR) is measured. An INR test can be done using a fingerstick blood draw at home, in a doctor’s office or by blood drawn in a laboratory. INR values are extremely important, and the correct values are crucial for individuals who have issues with mechanical heart valves, with atrial fibrillation and those who are at an increased risk of blood clot and stroke. Based on observations, problems with these test strips are not likely do be evident to patients. The previous recall was made by Roche and involved 1.1 million packages of CoaguChek XS PT Test strips that were distributed throughout the country from Jan 12th to October 29th, 2018. It is still in effect. The present recall involves Test Strips that that were manufactured by Roche and distributed by Terrific Care/Medex Supply and include catalog numbers that were not included in the recent Roche recall as these strips were unlabeled and not authorized for sale in the U.S. They were meant to be distributed by Roche Diagnostics only outside the country. It turns out that Terrific Care/Medex Supply purchased these strips from an unknown source and imported and sold them in the U.S. Like the recall before this, warnings have been issued by the FDA to make healthcare providers and patients aware of the fact that they should not rely on the test meter devices that use test strips to monitor the level of warfarin. Instead they should get blood drawn from a vein and measure the levels using laboratory methods. The previous warning was based on the fact that these CoaguChek XS PT strips were reporting erroneous and much higher INR values that could be detrimental in terms of the dose that prescribed to the patients based on the values. It could very well interrupt warfarin use and lead to an increase risk of blood clots. Hence FDA has requested all healthcare providers and patients to directly and voluntarily report INR test meter values to the FDA using the MedWatch, a voluntary reporting program of the FDA.

Facts About Blood

From Visually.

 

“Monitoring warfarin dosing is a critical part of using the drug properly to prevent and treat blood clots. Using faulty strips can lead to errors in medication dosage that could cause serious harm or death in some patients. That’s why it’s so concerning that this distributor continued to sell these test strips in the U.S. even though domestic sales had been stopped due to safety concerns. To reduce risks to patients, we’re warning health care providers and the public about the dangers associated with this product,” said FDA Commissioner Scott Gottlieb, M.D. “Distributing products that are not labeled or authorized for sale in the United States raises significant concerns for us in view of the serious safety issues with these test strip devices, and our work on this matter is not finished. Our top priority is the immediate safety of patients, and we’re taking steps to ensure the products that this company distributed are removed from the market.”

 

FDA approves the first therapy in adult patients with acquired thrombotic thrombocytopenic purpura (aTTP), a rare blood clotting disorder.


FDA recently approved the first therapy for the treatment of aTTP in adult patients [3]. The treatment is a combination of Cablivi (caplacizumab-yhdp) injection and plasma exchange and immunosuppressive therapy for patients with the rare and life-threatening blood clotting disorder. The application has been granted a Priority Review Designation. Cablivi has also obtained an Orphan Drug designation which provides incentives to encourage and assist the development of drugs for rare diseases. The approval was granted to Ablynx.

aTTP is an acquired blood disorder that leads to bleeding of small areas under the skin, low platelets and red blood cell counts and hemolytic anemia [4]. When a person’s body erroneously develops antibodies that block the activity of ADAMTS13 enzyme, the aTTP disorder becomes prevalent. ADAMTS13 is an enzyme that helps to control the activity of certain blood clotting factors. Those who develop this disorder end up having extensive blood clots in the small blood vessels throughout the body. Blood clots inherently are life-threatening as they can block off oxygen and blood supply to the major organs and can cause heart attacks and strokes. aTTP can also develop on the side in patients with HIV, cancer, lupus, during pregnancy or during bone marrow transplantation and chemotherapy. The common treatment for this involves plasma exchange and in some cases corticosteroid therapy or rituximab. For the approval, data was obtained from a randomized clinical trial of 145 patients who received either Cablivi or a placebo. Both the groups received the current standard of care of plasma exchange and immunotherapy. The trial showed much faster improvement in the platelet counts in patients treated with Cablivi when compared to placebo. There were lesser aTTP-related deaths and lower recurrence of aTTP during the treatment, for patients treated with Cablivi. The recurrence of aTTP in patients, in the overall study period along with a 28-day follow-up after the discontinuation of the drug, was found to be only 13% in the Cablivi-treated group and 38% in the placebo-treated group, showing statistical significance. Some of the common side effects observed during the clinical trials included bleeding of gums or nose and headache. The healthcare providers have been advised to monitor patients closely for excessive bleeding when administering Cablivi to those who are on anticoagulants.

“Patients with aTTP endure hours of treatment with daily plasma exchange, which requires being attached to a machine that takes blood out of the body and mixes it with donated plasma and then returns it to the body. Even after days or weeks of this treatment, as well as taking drugs that suppress the immune system, many patients will have a recurrence of aTTP,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Cablivi is the first targeted treatment that inhibits the formation of blood clots. It provides a new treatment option for patients that may reduce recurrences.”

 

FDA issues a Complete Response Letter to Sunovion for Apomorphine Sublingual Film (APL-130277).


FDA recently issued a Complete Response Letter (CRL) for the New Drug Application (NDA) for apomorphine sublingual film (APL-130277) to treat the OFF episodes in patients with Parkinson’s disease (PD) [5]. OFF episodes are defined by the re-emergence or worsening of Parkinson’s symptoms which are usually controlled by medications. After review of the submitted documents, the FDA has concluded that it is unable to approve the NDA for apomorphine sublingual film in its present form. Even though no additional clinical trials are required, the FDA has requested for more analyses and information. The CRL was issued to Sunovion, a global biopharmaceutical company that focusses on innovative application of science and medicine.

Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disease in which the dopamine producing cells are lost or damaged. It has widespread effects in about a million people in the U.S and about four to six million people globally. Various motor symptoms of the disease include rigidity and impaired movement and tremor at rest. Some of the non-motor symptoms are mood disorders and cognitive impairment. Along with Alzheimer’s, a large incidence of PD has been observed in the ageing population. OFF episodes are usually worsening of the motor and non-motor symptoms that are generally controlled by medications. It can occur in the morning and continue periodically throughout the day. The OFF episodes are usually represented in part, by stiffness, tremor and slow movement. These episodes could hinder one’s day to day activities. Within four to six months from the onset of PD, about 40 to 60 percent of patients exhibit OFF episodes and could worsen with the course of the disease. APL-130277 is a unique formulation of dopamine and apomorphine agonist, that is under development for the on-demand management of OFF episodes of PD. Apomorphine, as a subcutaneous injection, is currently an FDA approved product to treat acute, intermittent hypomobility and is associated with advanced stages of PD. The injection intends to convert the OFF state to an ON state and has been studied for treatment of motor OFF periods for up to five times per day and no sooner than two hours from the previous dose. A comparative biostudy in healthy volunteers and a dosing study in people with PD are the two Phase I trials for APL-130277 that the Michael J. Fox foundation has funded, in parts.

Parkinsons

From Visually.

 

“OFF episodes are a common and challenging part of Parkinson’s disease with few existing treatment options,” said Antony Loebel, M.D., Executive Vice President and Chief Medical Officer at Sunovion, Head of Global Clinical Development for Sumitomo Dainippon Pharma Group. “Sunovion remains committed to working with the FDA to address its requests so that we can bring apomorphine sublingual film to patients as expeditiously as possible.”

Roche announces the discontinuation of Phase III clinical studies of crenezumab in early Alzheimer’s disease.


Roche recently announced their decision to discontinue the CREAD I and CREAD 2 (BN29552 and BN29553) Phase III clinical studies of their investigational anti-beta amyloid molecule crenezumab in people with early sporadic Alzheimer’s disease (AD) [6]. The safety and efficacy studies conducted by the Independent Data Monitoring Committee contributed to the decision. Based on the study, it was highly unlikely for crezenumab to meet the primary endpoint of change from the baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) score. The overall safety study profile was like the previous trials. The data will be shared at an upcoming medical congress.

AD is a life-threatening, progressive disease of the brain, that gradually weakens the memory, problem solving skills and the performance of daily activities. The clinical manifestation of AD is a much later process as the original onset occurs way before any indication. In the early stages there might be a little difficulty in remembering, but in the latter stages the daily activities are almost always impaired. Out of the 50 million people affected with Dementia, 10 million new cases each year are found to have AD. The present available treatments can only reduce or weaken the symptoms, they are incapable of stopping the progression of AD as there are no known treatments targeting the underlying cause of the disease. Crenezumab functions by preferential binding to and removal of neurotoxic oligomers, a form of beta-amyloid. Crenezumab is an investigational, monoclonal antibody. An antibody backbone (IgG4) is designed to reduce the inflammatory response in the brain which could lead to a lower risk of certain MRI abnormalities known as ARIA (Amyloid-Related Imaging Abnormalities). This monoclonal antibody is a product of Roche and was discovered by AC Immune SA. To study the Phase III safety and efficacy of crenezumab, two randomized, double-blinded, global, placebo-controlled, parallel-group studies, CREAD 1 and 2, were designed. It involved 1500 people with early AD and with confirmed evidence of cerebral beta amyloid pathology. The doses used in this study were four times higher than that used in the Phase II trials. CREAD 1 was started in 2016 and CREAD 2 was initiated in 2017. Even though these Phase III trials will be discontinued, crenezumab will still be studied in the Alzheimer’s Prevention Initiative (API). The five-year study is in collaboration with the Banner Institute and is funded by the National Institute on Aging. Roche shall continue to conduct the ongoing clinical studies in Alzheimer’s disease, with GRADUATE Phase III trials with gantenerumab and the TAURIEL Phase II anti-tau trial.

Alzheimer

From Visually.

 

“While the results with crenezumab are disappointing, they meaningfully contribute to our understanding of Alzheimer’s disease,” said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development at Roche. “We gratefully acknowledge the participants in the CREAD trials and the efforts of everyone involved in this important programme. We remain dedicated to the Alzheimer’s community and will continue our Phase III GRADUATE trials with gantenerumab and Phase II TAURIEL trial with the anti-tau molecule RG6100, as well as our imaging and fluid-based diagnostic solutions.”

 

MeiraGtx and Janssen enter into a collaboration to develop and commercialize Gene therapy treatments for Inherited Retinal Disease.


MeiraGTx Holdings plc is a vertically integrated, clinical stage gene therapy company. It recently announced its broad strategic collaboration with Janssen Pharmaceuticals, Inc. to develop and commercialize gene therapies to treat inherited retinal diseases (IRDs) [7].

Inherited Retinal Diseases (IPD) are very rare eye conditions caused as a result of inherited gene mutations. It can be characterized by progressive retinal degradation. Eventually it leads to visual impairment causing blindness. MeiraGtx is at present, heavily invested in three ongoing IRD clinical programs. Another one is expected to enter into clinical development on 2019. They are also carrying out a number of pre-clinical IRD programs related to different gene mutations. Based on the agreement, the companies will collaborate in the clinical development of the leading IRD pipeline product of MeriaGTx. They have also agreed to work on other product candidates for X-linked retinitis pigmentosa (XLRP) and achromatopsia (ACHM) (caused by mutations in either CNGA3 or CNGB3).  MeiraGTx is expected to receive $100 million as an upfront payment in the form of cash with eligibility for additional payments up to $340 million, based on future sales milestones all related to CNGA3, CNGB3 and XLRP. They will also receive 20 percent of the annual net sales for these three programs. Janssen, meanwhile, will fund all clinical development and commercialization costs. All the pre-clinical programs of IRD for MeiraGTx will also be covered by this strategic collaboration and Janssen is scheduled to pay for most of the costs of this collaboration. The latter has the option of being a part of the programs coming out of the research collaboration when the IND application will receive clearance by the FDA. Janssen will thus fund all the operations (clinical development and commercialization) after the opt-in. MeriraGTx will receive a payment and development milestones and an un-tiered royalty on annual net sales of the commercialized product. Efforts will be made to develop AAV manufacturing technology and also to advance clinical and manufacturing supply agreements for research and clinical purposes by sharing the cost. The transaction will undergo the usual closing conditions. There will be an expiration of the applicable waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 and the closing is expected to happen in he first quarter of 2019.

https://youtu.be/kFQyjnmKHro

“We are very excited to collaborate with Janssen, a leader in the world of innovation and the creation of new medicines. By combining Janssen’s extensive clinical, regulatory and commercial expertise and global reach with MeiraGTx’s deep experience in gene therapy development and manufacturing, we aim to accelerate the development of our pipeline of potential IRD gene therapies to address the needs of patients globally,” said Alexandria Forbes, Ph.D., president and chief executive officer of MeiraGTx. “This important collaboration supports our leading position in gene therapy development and manufacturing and reaffirms our commitment to advancing a broad portfolio of breakthrough gene therapies that may improve the lives of patients suffering from IRDs worldwide.”

 

References:

  1. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm630151.htm.
  2. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm630408.htm.
  3. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm630851.htm.
  4. https://rarediseases.info.nih.gov/diseases/4607/thrombotic-thrombocytopenic-purpura-acquired.
  5. https://www.businesswire.com/news/home/20190130005919/en/Sunovion-Receives-Complete-Response-Letter-FDA-Apomorphine.
  6. https://www.roche.com/media/releases/med-cor-2019-01-30.htm.
  7. http://investors.meiragtx.com/news-releases/news-release-details/meiragtx-enters-strategic-collaboration-janssen-develop-and.

 

 

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: “Dorsal root ganglion cells from embryonic mice were cultured and stimulated to produce cyclooxygenase-2 (COX-2). Cultures were immuno-stained for neuron-associated tubulin (green), COX-2 (red) and DNA (blue). COX-2 is primarily expressed in neurons.”

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Disclaimer: 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 by authors and editors is a voluntary effort to popularize science for the public on behalf of PhD CSG. The sponsors do not have any influence on the nature or kind of the news/analysis reported in Onco-this-Week. The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of Club SciWri or PhD CSG. Examples of analysis performed within this article are only examples. They should not be utilized in real-world analytic products as they are based only on very limited and dated open source information. Assumptions made within the analysis are not reflective of the position of anyone volunteering or working for Club SciWri or PhD CSG. 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.

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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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