Editor’s Note: After the immense popularity of our weekly news series on oncology, ClubSciWri expands its repertoire of pharma-news blogging with Esha Sehanobish authoring the first edition of her very own series, Medness Plus. In this fortnightly series, she will be covering the top pharma news beyond our regular Oncology coverage. In the inaugural edition of Medness Plus, Esha talks about FDA’s approval of Eli Lilly’s Olumiant for adults suffering from Rheumatoid Arthritis and the restriction on CRISPR clinical trials for sickle-cell disease. We also have clinical trial updates on treating Multiple Sclerosis and severe Ulcerative Colitis along with a major industry collaboration to develop anti-HIV and anti-HBV therapies. We have made sure that this edition too is packed with an educational video on the 7-steps to Drug Discovery, infographics and cartoons for helping you grasp more than just news. We hope you enjoy reading our new series and stay tuned for the next Medness Plus!- Abhi Dey
Educational Video: 7-Steps to Drug Discovery- What does it take to bring a drug to a market? Join Dr. Derek Lowe, chemistry blogger for “In the Pipeline” and medicinal chemist for Vertex as he reviews the 7 steps in the drug discovery process. (Source- ACS Webinars)
Approvals and Rejections
FDA puts a brake on a CRISPR clinical trial to treat sickle-cell anemia
A gene-editing company called CRISPR therapeutics (NASDAQ-CRSP) based in Switzerland entered into a collaboration last December, with a biotech company called Vertex based in Boston (NASDAQ-VRTX). The idea was to develop a genetically engineered therapy to treat patients with sickle-cell anemia. They developed an ex-vivo therapy called CTX001 [1], which was meant to treat both sickle cell anemia and thalassemia. Both these diseases are caused by genetic mutations in the gene that codes for β-globin, a subunit of the hemoglobin protein that carries oxygen throughout the body. The therapy uses cells harvested from the patients. CRISPR then uses its gene-editing technique to create genetic changes in the cells outside the body so that there is an increased production of fetal hemoglobin (Hbf). These cells are then reinserted into the body of the patients to enhance the Hbf production which in turn helps to overcome the problems caused by hemoglobin deficiency. CTX001 was anticipated to go into clinical trials for sickle-cell anemia in the US in 2018.
FDA halts one of the first human #CRISPR studies before it begins: https://t.co/PLscDDMN5J
A trial planning to use the gene-editing tool CRISPR on sickle-cell patients has been put on hold because of unspecified questions from US regulators.
— Synthego (@Synthego) June 7, 2018
The US Food and Drug Administration has put a ‘clinical hold’ on the Investigational New Drug Application (IND) for the treatment using CTX001 [2]. The IND supporting the initiation of the Phase 1/2 trials of this therapy in sickle-cell anemia patients in the US was submitted to the FDA in April. But FDA has since put a brake in its initiation till additional information on their questions is made available by CRISPR therapeutics and Vertex. The CRISPR technology itself has been in the news for its ability to change lives. But its usage in solving disease-related issues is still at an early stage of implementation. It is still not an extensively explored area, and one needs to proceed with caution when it comes to gene-editing techniques since these techniques can have both beneficial and detrimental effects.
From Visually.
FDA approves a low drug-dose treatment for adults suffering from Rheumatoid Arthritis
The US Food and Drug Administration has recently approved the use of 2-mg once a day oral dose of Olumiant for adults who suffer from moderate to severe Rheumatoid Arthritis [3]. This announcement was made by Eli Lilly (NYSE – LLY) and Incyte Corporation (NASDAQ – INCY). This is supposed to be more effective in patients who do not experience a major success with other tumor necrosis factor (TNF) inhibitors therapies. It is best used in monotherapy or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (DMARDs). “We are pleased to provide Rheumatoid arthritis (RA) patients in the U.S. an effective treatment option with OLUMIANT, as people with RA who have an inadequate response to TNF inhibitors are generally considered to be some of the most difficult to treat RA patients,” said Christi Shaw, president, Lilly Bio-Medicines [4].
Congratulations to Delaware Bio members @Incyte and @LillyPad on the recent FDA approval of OLUMIANT (baricitinib) for rheumatoid arthritis. Read more about the approval here: https://t.co/unPiwVgjIT #arthritis pic.twitter.com/ohyQTrnwQu
— Delaware Bio (@Delaware_Bio) June 11, 2018
However, this approval comes with a “black box safety warning” and is only applicable for the lower dose. The warnings include thrombosis, malignancies and infection risks [4]. The FDA has also not cleared the higher 4mg dose for usage. These reasons have marked a heavy blow on the previously predicted “$1.8 billion sales by 2022”. The companies have also agreed to conduct a randomized clinical trial to determine the long-term efficacy of the drug.
Clinical Trials’ Updates
The results of stage 2 clinical trial of Mirikizumab against moderate to severe Ulcerative colitis
Ulcerative colitis is a global problem affecting millions of people worldwide. It is a chronic inflammatory bowel disease and is known to affect the colon in which the inflammatory reaction is restricted to the colon. Mirikizumab is a monoclonal antibody for the p19 subunit of interleukin 23 and is known for its effectiveness against inflammatory bowel diseases [5].
Lilly’s experimental colitis drug posts positive Phase 2 data: Eli Lilly’s experimental antibody mirikizumab led to higher rates of clinical response and remission in patients with ulcerative colitis treated in a mid-stage study, which the pharma touted… https://t.co/qgkzFbKhsV
— cafepharma (@cafepharma) June 6, 2018
Eli Lilly and company has recently released the results of the Phase 2 trial of Mirikizumab at Digestive Disease Week in Washington, D.C [3]. This trial studied the safety and efficacy of the drug in patients suffering from moderate to severe UC and who had not successfully responded to the conventional therapy. At the limit of 12 weeks, the primary and secondary endpoints that were considered involved endoscopic healing, endoscopic remission, symptomatic and clinical remission. Based on the data available the patients achieved a higher percentage of clinical remission, healing and endoscopic healing when compared to the placebo group. They are still working to look at the long-term effects, but for now, the outcome has been very positive. “Data from the Phase 2 trial indicate that if approved, Mirikizumab may be an effective treatment option for patients with moderate-to-severe UC”, said William J. Sandborn, M.D., Chief, Division of Gastroenterology, Professor of Medicine at the University of California San Diego School of Medicine [5]. The next, almost certain step, is the advancement to the Phase 3 trial for the drug against Ulcerative Colitis.
The effects of multiple sclerosis new drug, Ocrevus, on vaccine responses
Ocrevus is a prescribed Roche medication that is used to treat relapsing or primary progressive form of multiple sclerosis in adults [6]. The approval by FDA happened in March 2018. At that time the only reported and most common side effects associated with Ocrevus in case of all Phase III studies were upper respiratory tract infections and infusion reactions ranging from mild to moderate in severity [7].
Roche’s multiple sclerosis drug Ocrevus lowered patients’ vaccine responses: study | FiercePharma https://t.co/TYGWcRFWYa pic.twitter.com/nmMeYfQK1q
— AIHCP (@AIHCP) June 9, 2018
In the Phase IIIb trial sponsored by Roche, the new data shows that the effectiveness of some vaccines reduce when a patient is on Ocrelizumab [8]. 100 multiple sclerosis patients who were on Ocrevus were tested for immune responses against vaccines such as tetanus, seasonal flu and pneumococcal polysaccharide vaccine (PPV). The results showed an attenuated humoral response to the mentioned vaccines. Due to the mode of action of the drug, the result wasn’t totally unexpected. It works by reducing the activity of CD-20 expressing B-cells which are in turn responsible for producing antibodies in humoral response, thus explaining the reduced responses to vaccines. Keeping this in mind, it should also be mentioned that there are high hopes for this drug since it is the first and only medicine for both primary progressive and relapsing forms of MS and its first-quarter sales has made it one of the most successful drugs for Multiple sclerosis.
Healthcare Industry News
Alliance to develop therapeutics against HIV and Hepatitis B infections
Hookipa Biotech is a clinical stage company that develops next-generation immunotherapies to treat cancer and infectious diseases using arenavirus vector. Gilead Sciences Inc. is a biopharmaceutical company that develops medicines against life-threatening diseases. According to a recent announcement, these two companies have entered into a research collaboration and license agreement [9]. Based on this collaboration, Gilead now has exclusive rights to Hoopkia’s Thera T and Vaxwave arenavirus vector-based techniques for hepatitis B virus (HBV) and human immunodeficiency virus (HIV).
@HookipaBiotech and @GileadSciences Enter into a Collaboration and License Agreement to Develop Immunotherapies Against #HIV and HepatitisB #HBV – See full Press Release https://t.co/HZ9UUuLAff pic.twitter.com/SalXQ2u5mv
— Hookipa Biotech AG (@HookipaBiotech) June 5, 2018
As per the agreement, Gilead will make an upfront payment of $10 million. Based on achievements from developments, regulatory and commercial milestones, Hoopkia will be eligible to receive milestone payments up to a total that is more than $400 million [10]. They will also be able to receive tiered royalties on overall sales. “We are convinced that Hookipa’s unique therapeutic vaccine technology, which has demonstrated excellent safety and immunogenicity in Phase 1 clinical studies, has strong potential to have a synergistic effect with other Gilead cure efforts in both diseases areas. Our ultimate long-term goal is to eliminate the need for life-long antiviral therapy for millions of patients around the world,” said Bill Lee, Ph.D., Executive Vice President of Research, Gilead.
Cell massively infected with HIV, showing the budding of the viral particles across the cell surface (scanning electron microscopy). Image source: Wikimedia Commons (By Roingeard – Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=45063779)
Novel m-RNA technique to be the basis for collaboration and $45 million deal
Sanofi Pasteur and Translate Bio have agreed to enter into a collaboration to use the novel m-RNA technique of the latter to develop vaccines for infectious diseases. Translate Bio formerly known as RaNA therapeutics is a Lexington, MA-based firm with expertise on mRNA research and development. The agreement is a multi-year research and development collaboration and exclusive license agreement with Sanofi Pasteur, the vaccine global business unit of Sanofi (NYSE: SNY) to develop mRNA based vaccines for up to five undisclosed infectious disease pathogens.
Sanofi builds on mRNA alliances with an $850M pact for Ron Renaud’s Translate Biohttps://t.co/Z9OnH7WdTR
— John Carroll (@JohnCendpts) June 11, 2018
There will be an upfront payment of $45 million by Sanofi Pasteur to Translate Bio [11]. The latter could receive up to $805 million which would include sales, regulatory etc. related milestones across different vaccines. They are also eligible for royalty payments associated with the worldwide sales of the vaccine. The exclusive worldwide commercialization rights remain with Sanofi Pasteur while they fund the entire research project. “We believe that this partnership values potential; of our mRNA platform, and also enables us to apply our mRNA technology beyond the current therapeutic applications that we are pursuing in cystic fibrosis and ornithine transcarbamylase (OTC) deficiency, ultimately advancing our goal of delivering innovative medicine to patients,” said Ronald Renaud, Chief Executive Officer, Translate Bio.
Nimbus therapeutics bags a grant of $65 million to finance their clinical endeavors
Nimbus Therapeutics, a Cambridge, MA-based biotech company, was established in 2009. It uses a chemical-simulation software to help researchers figure out the mode by which the drugs bind to targets. This will assist further in designing drug targets. Nimbus has for a long time associated itself with larger companies by collaborating with them and selling them their discoveries. But their present goal is to invest and get their discoveries to clinical trials. Based on a recent announcement, they have acquired $65 million to speed up some of their long-awaited projects and extend their research into areas including immunology, oncology and metabolic diseases [12].
Today Nimbus announced it has raised $65 million to accelerate the company’s pipeline progress and expansion into new high-value targets of interest. Read the full press release here: https://t.co/YBVXImzOoi pic.twitter.com/brvoqXE0ih
— Nimbus Therapeutics (@NimbusTx) June 5, 2018
Its investors include Atlas Venture, SR One, Lilly Ventures, Bill Gates, Pfizer Venture Investments, Lightstone ventures and Schrodinger. Nimbus therapeutics has already made significant progress in alliance with Celgene in research areas like inhibitors of tyrosine kinase 2 and antagonists of STING (stimulator of interferon genes). Research conducted by them has generated novel, highly potent small molecules that look very promising based on their preclinical data. The grant will help them advance some of these studies as mentioned by Jeb Keiper, Chief Financial Officer and Chief Business Officer, “This most recent infusion of capital from our investors, together with proceeds from business development activity, enables Nimbus to remain a privately held LLC organization, which has allowed us to transact multiple deals with world-leading partners such as Gilead, Celgene, and Genentech.”
References:
[1] CRISPR Therapeutics, Our programs, Our pipelines (Web): http://crisprtx.com/our-programs/our-programs.php?section=hemoglobinopathies
[2] CRISPR Therapeutics and Vertex provide update on FDA review of Investigational New Drug application for CTX001 for the treatment of sickle cell disease, CRISPR Therapeutics news release, Web. http://ir.crisprtx.com/phoenix.zhtml?c=254376&p=irol-newsArticle&ID=2351354.
[3] Eli Lilly, Press release, (Web): https://www.lilly.com/newsroom/press-releases.
[4] FDA approves OLUMIANT (baricitinib) 2-mg tablets for the treatment of adults with moderately-to-severely active Rheumatoid Arthritis. (Web): https://investor.lilly.com/news-releases/news-release-details/fda-approves-olumiantr-baricitinib-2-mg-tablets-treatment-adults.
[5] DDW 2018: Patients with moderate-to-severe Ulcerative Colitis achieved clinical and endoscopic remission with Mirikizumab in Phase 2 trial, (Web): https://investor.lilly.com/news-releases/news-release-details/ddw-2018-patients-moderate-severe-ulcerative-colitis-achieved.
[6] Ocrevus, (Web): https://www.ocrevus.com.
[7] Roche, Press release, (Web): https://www.roche.com/media/releases/med-cor-2017-03-29.htm.
[8] Stokmaier, D., et al, Effect of ocrelizumab on vaccine responses in patients with multiple sclerosis, Neurology, April 25, 2018.
[9] Gilead, Press Release, (Web): http://www.gilead.com/news/press-releases.
[10] Hookipa and Gilead enter into a collaboration and license agreement to develop immunotherapies against HIV and Hepatitis B, (Web): http://www.gilead.com/news/press-releases/2018/6/hookipa-and-gilead-enter-into-a-collaboration-and-license-agreement-to-develop-immunotherapies-against-hiv-and-hepatitis-b.
[12] Our source version is based on:
https://www.businesswire.com/news/home/20180605005214/en.
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.
Cover image: (Wikimedia Commons) Description Hands of a scientist, under a sterile hood, preparing the carcinoembryonic antigen (CEA) vaccinia used to try to prevent cancer. The scientist is diluting the concentrated vaccinnia virus into a dose level appropriate for administration to a patient. This vaccinnia marks any cancer cells expressing the CEA. Source National Cancer Institute
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