Editor’s Summary: In the current edition of Medness Plus, Esha Sehanobish updates you about the latest pharma news from Biogen, Novartis, Amgen, Akebia, Eisai, Keryx in areas of Alzheimer’s, Kidney Disorders and Migraine along with a major acquisition news in the antibody-based therapeutic area. Also in this edition is the news about a multi-center clinical trial discontinuation by Summit Therapeutics owing to a Phase 2 trial failure. Wondering which disease this trail was for? Read on to know more.- Abhi Dey
Pharma News and Drug Trials
New data from Biogen and Eisai shows hope for failed Alzheimer’s study
Biogen (NASDAQ – BIIB), a Cambridge, Massachusetts based biotech company and Eisai Co. Ltd, a Tokyo based company recently announced positive results for Phase II studies for BAN2401, an anti-amyloid beta protofibril antibody, in 856 patients with early Alzheimer’s disease [1]. As per the study, statistical significance was observed for the predefined endpoints where the efficacy was determined at 18 months. There was a reduction in the accumulation of amyloids in the brain as determined using amyloid-positron emission tomography and exhibited a slow progression in Alzheimer’s disease composite score (ADCOMS). This is very encouraging considering that in late 2017, the companies hit a road-block as the drug was unable to show significant changes in assessment scores when patients in early stages of Alzheimer’s were investigated [2]. However, the studies were pursued even after that for comprehensive analysis after 18 months.
new Alzheimer’s drug-Biogen and Tokyo-based Eisai -“statistically significant” evidence that the drug, BAN2401, can slow progression of the deadly disease. Investors are predicting the final drug has a 50% chance of getting approvedhttps://t.co/aYsxd0PNL3 pic.twitter.com/iitrEYtHNH
— Artstrada Magazine (@Artstrada) July 14, 2018
BAN2401 is a human monoclonal antibody that was developed as an effort to treat Alzheimer’s disease. It functions by selectively binding to eliminate and neutralize Aβ aggregates that are known to result in neurodegeneration in patients who have Alzheimer’s. This could also result in delaying the progression of the disease. Eisai obtained the global rights to manufacture, study and market BAN2401 in 2007. Later in March 2014, they formed an alliance with Biogen for the development and commercialization of the drug. Based on the data, Study 201, 856 patients with mild cognitive impairment and Alzheimer’s dementia with confirmed amyloid pathology, were a part of the trial. The efficacy was then investigated at 18 months. It was seen that there was a statistically significant slowing in the progression of the disease when the patients received the highest dose of 10 mg/kg, biweekly. BAN2401 also showed acceptable tolerability through the 18 months of drug administration. Some adverse reactions that were observed were mostly mild to moderate infusion-related issues. “This is the first late-stage anti-amyloid antibody study to successfully achieve statistically significant results at 18 months, further validating the amyloid hypothesis,” said Lynn Kramer, M.d., Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai. “The prospect of being able to offer meaningful disease-modifying therapies to individuals suffering from this terrible disease is both exciting and humbling,” said Alfred Sandrock, M.D., Ph.D., executive vice president and chief medical officer at Biogen.
From Visually.
Akebia Therapeutics and Keryx Biopharmaceuticals merge to develop and commercialize drugs to treat patients with kidney disorder
The two companies Akebia Therapeutics (NASDAQ: AKBA) and Keryx Biopharmaceuticals (NASDAQ: KERX) announced recently that they were forming an alliance under which the companies will combine in an all-stock merger [3]. An all-stock merger essentially means that the shareholders of the merging companies are entitled to the same value of the shares in the new company as they were in the old one. The alliance is supposed to create a fully integrated biopharmaceuticals company that will focus on chronic kidney diseases as per the expertise of Keryx Biopharmaceuticals with a total evaluation of $1.3 billion.
Akebia, Keryx to merge, creating $1B kidney disease company https://t.co/uZZFhfV3Bd #CKD #MnA pic.twitter.com/4W2WgszRCo
— Ozmosi (@OzmosiHealth) July 10, 2018
Based on the agreement, Keryx shareholders will receive 0.37433 common shares of Akebia for each share of Keryx that they own. Akebia stockholders will thus own 49.4 percent whereas Keryx will end up with 50.6 percent. Baupost Group, the key stock and debt holder of Keryx will own 21.4 percent of the company and has entered into a voting agreement in support of the transaction. The combined company will have $453 million in cash. Vadadustat is a product of Akebia and is presently in Phase3 development for the treatment of anemia caused due to chronic kidney disease. It is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). Its mechanism of action mimics the effects of height on the availability of oxygen. FDA approved Auryxia (ferric citrate) is a product of Keryx and is used to control the phosphorus levels in the serum of adult patients suffering from chronic kidney disease and who are on dialysis. Once Vadadustat gets approved, nephrologists will have a broader range of drugs at their disposal for treating both dialysis and non-dialysis dependent patients.
Video Source: Wikimedia Commons- What is chronic kidney disease (CKD)? Chronic kidney disease is described as any loss of kidney functioning that develops beyond a 3 month period. Sources: https://www.kidney.org/atoz/content/about-chronic-kidney-disease Pathoma by Dr. Sattar (Pg 132-133) Harrison’s Principles of Internal Medicine 18th Ed. UpToDate; http://emedicine.medscape.com/article/238798-overview#a4 ; http://thelancet.com/journals/lancet/article/PIIS0140-6736(16)32064-5/fulltext ; https://www.kidney.org/sites/default/files/02-10-6785_HBE_Hyperkalemia_Bulletin.pdf; https://www.kidney.org/sites/default/files/01-10-7278_HBG_CKD_Stages_Flyer3.pdf
“Bringing Keryx together with Akebia represents a unique, value-enhancing opportunity for stakeholders of both companies. I look forward to working with our management team during this transition period to continue to deliver on our mission to bring innovative medicines to people living with kidney disease,” said Jodie Morrison, Interim Chief Executive Officer of Keryx. “Combining Akebia and Keryx creates a leading renal company and provides it with the infrastructure to maximize the market potential of Auryxia and build launch momentum for vadadustat in the United States, subject to FDA approval. I look forward to leading the talented teams of both Akebia and Keryx as we work to establish new standards of renal care and unlock growth potential for shareholders,” said John P. Butler, President and Chief Executive Officer of Akebia.
Amgen and Novartis release new data that show the long-term efficacy, safety and tolerability of Aimovig (erenumab) in patients dealing with chronic and episodic migraine
Amgen (NASDAQ: AMGN) and Novartis (NYSE: NYS) recently announced the results of two open-label extension studies involving Aimovig, in patients suffering from chronic and episodic migraine [4][5]. Open-label extension studies usually include a double-blind randomized placebo-controlled trial of a new drug. Once that is over, the participants are invited to enroll in an extension study which is usually longer than the randomized trial. In this extended open-label trial, the data reinforced the established safety and efficacy of Aimovig in long-term use. The data will be presented at the 60th Annual Scientific Meeting of the American Headache Society in San Francisco.
Amgen, Novartis ‘overwhelmed’ by early interest in migraine drug Aimovig: expert https://t.co/NAh1smECF9 pic.twitter.com/PDO4xQVL7L
— Intelligence Pharma (@IntelligencePh1) July 9, 2018
Aimovig works by blocking CGRP-R, calcitonin gene related peptide receptor and was approved by FDA in May 2018 for treating chronic migraine. Chronic migraine patients generally were considered to experience migraine for 15 or more days per month. In this study, the primary endpoint was long-term efficacy and the secondary endpoint was the efficacy. When the safety results were compared to the already established safety profile, it was found to be consistent. There were sustained benefits for a year as far as efficacy is concerned. The reported adverse effects included upper respiratory tract infections, sinusitis and migraine.
From Visually.
“Following FDA approval, with European approval anticipated in the coming months, we are very pleased to report positive long-term safety and efficacy results for Aimovig,” said Danny Bar-Zohar, Global Head of Neuroscience Development at Novartis Pharmaceuticals. “For patients who have suffered from migraine for years, these new data further confirm that Aimovig may offer long-term sustained and safe relief from migraine and the heavy burden it imposes.” Amgen and Novartis entered into a global collaboration in August 2015 to develop and commercialize treatments in the field of migraine and Alzheimer’s disease. Amgen has the commercialization rights to the drug in Japan whereas the rights for the rest of the world lies with Novartis.
Summit Therapeutics decides to discontinue work on a Duchenne drug due to Phase 2 trial failure
Summit therapeutics is a biopharmaceutical company that focusses on the discovery and development of drugs against infectious diseases (mainly C. difficile infection) and Duchenne muscular dystrophy, a neuromuscular disease. They were involved in carrying out PhaseOut DMD (Duchenne Muscular Dystrophy) which was a multicenter, open label Phase 2 clinical trial of ezutromid. This drug was being investigated as a potential candidate to treat patients with DMD. The company recently announced that the trial did not meet the primary and secondary endpoints after 48 weeks. Due to this, the company has decided to discontinue further development of ezutromid. They will now focus on their other pipeline drugs with newer antibiotic mechanism [6][7].
Summit Therapeutics Ends Development of Ezutromid Therapy for DMD After Trial Failure https://t.co/pHRGGCf6Pv pic.twitter.com/6ZFUgpBuCJ
— BioNews Services (@bionewsservices) June 29, 2018
Duchenne muscular dystrophy is characterized by severe and progressive muscle weakness which can initiate in boys as young as four years of age. Within a few years they can have significant degradation in their condition with muscle loss in the upper leg followed by its progression to their upper arms. Summit’s ezutromid was aimed at increasing the production of a protein called utrophin. This protein is essential in healthy muscle functioning. Hence the idea here was to enable the production by the drug. The study that was carried out enrolled 40 boys in an open-label Phase 2 trial. It was reported that the measures of muscle improvement such as myosin development which were observed after 24 weeks, could not be sustained when the 48-week trial period was completed. Summit had previously entered into an agreement with Sarepta therapeutics in 2016 that involved research, development and commercialization of ezutromid and other novel therapies in treating patients suffering from Duchenne muscular dystrophy.
Image Description: Duchenne muscular dystrophy (“pseudo-hypertrophic spinal paralysis” in a child) (from Wikimedia Commons)
Glyn Edwards, Chief Executive Officer of Summit said, “These data come as a great disappointment to us and to all those living with DMD. While we believe utrophin modulation could still have a place in the treatment of DMD, it is clear that ezutromid is not providing a benefit for patients. We therefore feel that our resources are better focused on the development of our promising pipeline of new mechanism antibiotics.”
CARB-X awards Summit Therapeutics with a grant to encourage the development of new mechanism Gonorrhea antibiotics
In a recent announcement, Summit Therapeutics plc (NASDAQ: SMMT) mentioned that they have been awarded up to $4.5 million from CARB-X, a non-profit public-private partnership that is committed to accelerate research in developing antibiotics against drug-resistant bacteria. The motive of this grant is to support Summit in the development of its new mechanism gonorrhea treating antibiotics [8]. Based on the agreement, Summit will receive an initial $2 million in part to determine the preclinical candidate from Summit’s gonorrhea series. The remaining $2.5 million is supposed to be exercised by CARB-X as and when substantial achievements and milestones will be attained. This non-dilutive funding could support development through the completion of phase 1 clinical trial. It is known that non-dilutive financing does not require the company’s share to be sold nor does it cause any dilution of the existing shareholders [9].
@CARB_X backs @Summitplc to develop a new class of antibiotics to treat Gonorrhoea Superbug infections. #PoweredbyCARBX portfolio now has 10 new classes of antibiotics; 34 research projects to fight #antibioticresistance and #StopSuperbugs. https://t.co/ehjltSAjJx pic.twitter.com/FrkmoQRD6B
— CARB-X (@CARB_X) July 10, 2018
Summit has recently identified a series of new mechanism disease antibiotics which have great potential against different N. gonorrhea strains. It has also shown efficacy against multidrug-resistant ones. Gonorrhea has been identified to be an urgent bacterial threat by the US Center for Disease Control (CDC) due to a reduction in options to treat the disease. Hence Summit therapeutics is currently researching newer antibiotics to treat C.difficile infections and gonorrhea using their Discuva Platform that combines bioinformatics and transposon technology to create compounds against pathogen libraries. “Drug-resistant gonorrhea is an urgent and growing public health problem around the world, affecting the health and quality of life of millions of people,” said Kevin Outterson, Executive Director of CARB-X. Glyn Edwards, Chief Executive Officer of Summit, said, “This CARB-X collaboration and funding is important to us as we aim to pioneer a new era in antibiotic innovation and allows us to accelerate the development of our first series of new mechanism of action gonorrhea compounds.”
Otsuka pharmaceutical widens its domain by the acquiring Visterra for $430 million
It was recently announced that Otsuka pharmaceuticals and Visterra have entered into an acquisition agreement in which the former will acquire the latter in a $430 million all-cash transaction [10]. Hematological cancers, psychiatric and neurological disorders and kidney, cardiovascular and infectious diseases are some of the areas of specialization for Otsuka. Visterra’s Hierotope platform, on the other hand, uses experimental and unique computational developments to enhance the antibody-based therapeutic area. Therefore, the idea behind the acquisition is that Otsuka now wants to expand its domain of drug discovery by focusing on antibody development to increase the efficiency of drug-based treatments.
Tech update: Otsuka to acquire antibody developer Visterra in $430M deal | Bio Tech #science https://t.co/wfjXtZ2iwf pic.twitter.com/3MfZGjKg43
— Prosyscom Pvt.Ltd (@prosyscom_it) July 12, 2018
“I am highly gratified that Visterra’s exceptional antibody platform technology, promising pipeline and talented researchers will join up with Otsuka. By collaborating and reinforcing each other’s culture, human ingenuity and technology, we hope to help fulfill Visterra’s promise as a powerful new drug creation engine and expand Otsuka’s research horizons,” said Tatsuo Higuchi, president and representative director of Otsuka Pharmaceutical Co., Ltd. “This transaction affirms the power of Visterra’s novel technology platform, the promise of our product candidates, and the value our employees and shareholders have created. Our two companies share a common culture of creativity and innovation, and commitment to patients with kidney diseases, cancer and other hard-to-treat diseases. Joining forces with Otsuka will provide Visterra the resources, support and commitment to accelerate development of our pipeline and fully realize the potential of our technology platform,” said Brian J. G. Pereira, MD, CEO of Visterra.
References:
[8] https://www.summitplc.com/wp-content/uploads/2018/07/2018_RNS_31-CARBX-Gonorrhoea-Award-FINAL.pdf.
[9] http://blogs.nature.com/tradesecrets/2012/10/09/non-dilutive-financing-for-biotech-startups.
[10]https://www.businesswire.com/news/home/20180711005169/en/Otsuka-Pharmaceutical-Acquire-Visterra.
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 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.
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