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FDA authorizes the interoperable insulin pump to allow patients with diabetes to customize their treatment.


The FDA recently announced the approval for the marketing of Tandem Diabetes Care t: Slim X2 insulin pump with interoperable technology [1]. The technology will be used to deliver insulin under the skin, to adults and children with diabetes. This ACE (Alternate Controller Enabled) infusion pump, is a novel insulin interoperable pump that can be used with a combination of different components in the diabetes therapy system allowing patients to build their treatment management based on their preferences. The other components involved along with the insulin pumps include devices for blood glucose monitoring, for continuous glucose monitoring, automated insulin dosing (AID) systems and other devices. The marketing authorization for the t: Slim X2 insulin pump with interoperable technology was granted to Tandem Diabetes Care, by the FDA. FDA is also in the process of establishing special controls along with the authorization. These special controls will include requirements for assuring efficacy, reliability, accuracy, cybersecurity and clinical importance of ACE infusion pumps. It will also contain a description of the studies and the data that will summarize acceptable performance by the device. The effectiveness and safety of a device will only be accepted when these special controls are met along with the general controls.

Diabetes is a widespread disorder and almost 10 percent of Americans are diagnosed with it. Diabetes affects the body’s ability to generate or properly use the hormone insulin. A patient with diabetes thus ends up having various other non-related complications which could serve as a hindrance especially during times of surgery. Till now, FDA has cleared insulin pumps as devices that can be used on its own as class II moderate-risk devices. There are some that have been approved by the FDA as a single, pre-defined diabetes management system which belongs to the class III, highest-risk devices. Since the t: Slim X2 can also be used in combination with other components, the application was reviewed under the de novo premarket review pathway, usually used for a novel, low-to-moderate-risk devices of a new type. The interoperable pump works by delivering insulin under the skin at set or variable rates.  When connected with other diabetes management devices such as the AID system, the pump can directly communicate and receive dosing options. When it is not connected, it can infuse insulin on its own. The AID systems include a CGM, a pump and software to control the system. The performance data of t: Slim X2 was thoroughly examined by the FDA that showed dose accuracy and reliability at the rates and volumes programmed by the user. The communication skills of the pump with the other devices was also reviewed before the approval. After review, it was concluded that the risks in using this particular pump was similar to that associated with other infusion pumps and could cause infection, bleeding, pain or reactions to the skin such as swellings, redness, itching etc. Some other risks include blockage and air bubbles in the tubing. Incorrect drug delivery could result in hypoglycemia, hyperglycemia and diabetic ketoacidosis. Specific risks for ACE insulin pumps include wrong delivery of drugs caused by faulty communication between devices.

Diabetes in the US

From Visually.

 

“Diabetes is a complicated disease that requires close monitoring and carefully tailored treatments. We’ve heard from the patient community that having the ability to customize their own diabetes management devices is important to them. Advances in digital health make more tailored approaches to diabetes care possible,” said FDA Commissioner Scott Gottlieb, M.D. “The marketing authorization of the first ACE insulin pump intended for interoperable use has the potential to aid patients who seek more individualized diabetes therapy systems and opens the door for developers of future connected diabetes devices to get other safe and effective products to patients more efficiently. Because the FDA’s action creates a new regulatory classification, future ACE insulin pumps will be able to go through the more efficient 510(k) review process, helping to advance this innovative technology. We’re committed to advancing new ways to accelerate the development of innovations that can improve patient care while strengthening our pre- and post-market tools for determining the safety and effectiveness of these new technologies.

 

FDA approves the use of Egaten, for the treatment of a tropical disease called fascioliasis.


FDA recently announced the approval of Egaten (triclabendazole) for the treatment of patients with fascioliasis in patients aged six years and above [2]. It is the first and only approved therapy for the neglected tropical disease. It is expected to become accessible to patients affected by fascioliasis not only in the US but all over the world. The approval was given to Novartis.

Fascioliasis is also known as liver fluke infestation and affects 2.4 million globally. It is considered to be a neglected tropical disease that could put an additional 180 million at risk of infection. Fascioliasis is caused by two species of flatworm or trematodes (Fasciola gigantica or Fasciola hepatica) that thus affecting the liver. The infection occurs through larvae contamination in water or raw and uncooked food. The larvae then develop into adult worms in the biliary tract. If left unnoticed and untreated, fascioliasis can cause discomfort and pain. Symptoms include fever, diarrhea, eosinophilia, nausea, abdominal pain. Children infected with fascioliasis can have high fever, anemia and an enlarged liver. For adults, the latter stage could develop into a chronic or obstructive phase. More than 70 countries around the world have reported human cases of fascioliasis indicating that it is prevalent worldwide. Currently, there is no approved treatment for fascioliasis, which makes Egaten the first of its kind to be approved by the FDA. It is the only medicine recommended by the WHO and has made it on to the WHO Model List of Essential Medicines. In the past, its supply was only restricted to epidemic outbreaks and was occasionally used in endemic countries. WHO had the sole authority to supply it when needed. With the present approval by the FDA, marketing and availability are expected to be much easier. Since fascioliasis is considered to be a neglected tropical disease, the approval resulted in a Priority Review Voucher. Since 2005, Novartis has donated continuously to the WHO to help treat fascioliasis patients in more than 30 countries.

“Novartis has a long-standing commitment to addressing global health challenges and supporting disease elimination efforts, in diseases such as leprosy, malaria and fascioliasis,” said Vas Narasimhan, CEO of Novartis. “Today’s FDA approval of Egaten is another important milestone that we believe will help further expand access to this one-day treatment, taking us a step closer toward disease elimination.” “This FDA decision is welcome news for millions who suffer or are at risk of fascioliasis and removes a major hurdle in expanding treatment to countries where it is most needed,” said Dr Mwelecela Malecela, Director of the Department of Control of Neglected Tropical Diseases at the WHO. “We are thankful to Novartis for their sustained decade-long commitment in tackling yet another disease of poverty.”

 

FDA generates boxed warning for an increased risk of death with Uloric.


FDA recently reviewed and concluded that there is an increased risk of death associated with Uloric (febuxostat) when compared to allopurinol, another medicine used for treating gout [3]. A detailed review was done of the clinical trial focusing on safety and the inference from it was that treatment with Uloric could lead to an increased risk of death and also death from all causes. Uloric was approved first in 2009 to Takeda Pharmaceuticals and “Warning and Precaution” regarding possible cardiovascular events in patients treated with Uloric was also included. FDA had asked the manufacturing company to carry out an extensive post-market clinical trial.

Gout / Podagra

From Visually.

 

Uloric was approved to treat gout, a type of arthritis, in adults. Uric acid built up is the primary cause of gout and symptoms include swelling, pain in one or more joints and attacks of redness. Uloric functions by lowering the levels of uric acid in the blood. Around 8.3 million adults in the US are affected by gout. It is a chronic disease with limited medicines available for the treatment. The approval in 2009 was based on a study performed on 6000 patients with gout who were treated either with allopurinol or with Uloric. The results reflected the fact that overall, Uloric did not increase the risk of combined effects of heart-related issues when compared to that of allopurinol. However, upon individual evaluation, Uloric exhibited an increased risk of heart-related deaths and deaths from all causes. For every 1000 patients, 15 deaths were from heart-related causes for those on Uloric when compared to 11 for every 1000 patients treated with allopurinol. 26 patients died from any cause per 1000 patients treated with Uloric as compared to 22 per 1000 patients treated with allopurinol. It thus showed a combination of heart-related death, non-deadly heart attack, non-deadly stroke and unstable angina. Due to these observations, FDA has decided to update the prescribing information for Uloric and include the Boxed warning and a new patient Medication Guide. They limit its use to individual patients who are not treated adequately or who exhibit side effects during the use of allopurinol. Boxed warning, also known as Black box warning, usually appears on the drug’s label and is added to highlight severe or life-threatening events [4]. Patients have been advised to report to their healthcare professionals in case of a history of heart-related disorders if they have been prescribed Uloric. In case a patient on Uloric experiences shortness of breath, chest pain, rapid heartbeat, dizziness, sudden severe headaches, they are advised to seek medical emergency services at the earliest. A decision about continuing Uloric should only be taken after consultation with a health care professional. They have been recommended as well to encourage their patients to report any abnormalities.

 

Johnson and Johnson receive approval for SPRAVATOTM (esketamine) for adults with treatment-resistant depression.


Johnson and Johnson recently announced the affirmative decision taken by the Psychopharmacologic Drug Advisory Committee and Drug Safety and Risk Management Advisory Committee for the approval of SPRAVATO nasal spray CIII for adults with treatment-resistant depression [5]. The final vote recorded was 14 yes, 2 no and 1 abstain. SPRAVATO works in a different way than the presently available therapies for major depressive disorders (MDD). It is an investigational prescription therapy. Janssen has already submitted a New Drug Application (NDA) to the FDA for SPRAVATO’s approval.

A Short History of Depression

From Visually.

MDD is a global problem and is known to affect around 300 million people of all ages, worldwide. Those that have major depressive disorder also experience continuous suffering from biologically based diseases which affect their day to day activities. Even though there are some available treatments, a majority of patients are resistant to these treatments. Esketamine is a glutamate receptor modulator that restores synaptic connections in brain cells in people with MDD. It is an investigational product that is currently under development as a part of Janssen’s global program. FDA has already granted a Breakthrough Therapy Designation for esketamine for the treatment-resistance depression and MDD, with a risk of suicide. The suggestion was based on data from the safety and efficacy profile of five Phase 3 studies in patients with treatment-resistant depression: three short-term studies, one maintenance of effect study and one long-term safety study. Further studies were carried out that showed that esketamine nasal spray along with a newly initiated oral antidepressant provided statistically significant and much-improved results. Those that participated in the studies received the target nasal spray or placebo in addition to the oral antidepressant at the start of the treatment phase. After 52 weeks, the long-term safety study showed the good tolerability of esketamine with no new safety signals, when compared to the short-term (4-week) studies. Some of the treatment-related adverse reactions included dizziness, increased blood pressure etc.

“We are pleased with the advisory committees’ vote and their recommendation to approve SPRAVATOTM as a potential therapy for adults living with treatment-resistant depression,” said Husseini K. Manji, M.D., Global Head, Neuroscience Therapeutic Area, Janssen Research & Development, LLC. “Our comprehensive research program for esketamine nasal spray supports a positive benefit-risk profile for adults with treatment-resistant depression.”

 

 

Servier, Amgen and Cytokinetics announce the beginning of the second phase 3 clinical trial of Omecamtiv Mecarbil in patients with heart failure.


The three companies Cytokinetics Incorporated, Servier and Amgen recently announced the start of enrollment for the second Phase 3 clinical trial of Omecamtiv mecarbil, called METEORIC-HF [6]. The abbreviation stands for Multicenter Exercise Tolerance Evaluation of Omecamtiv Mecarbil Related to Increased Contractility in Heart Failure. This is a novel cardiac myosin activator which is under research as a potential treatment of heart failure with decreased ejection fraction (HFrEF).

Heart failure is a serious condition affecting more than 26 million people globally. It is a chronic condition which could lead to reduced left ventricular function. Older population aged 65 and above are mainly affected by heart failure with the majority leading to hospitalization and readmission. Based on available data, one in five people above the age of 40 is expected to be at a higher risk of heart failure and about 50 percent of those diagnosed with the disorder will die within a period of five years after the initial hospitalization. Omecamtiv Mecarbil is a cardiac myosin activator that works by binding to the catalytic domain of myosin. Cardiac myosin is a protein in the cardiac muscles that is responsible for the conversion of chemical energy into mechanical energy leading to cardiac contraction. Available data shows that cardiac myosin activators increase cardiac contractility without having much effect on intracellular myocyte calcium concentrations or myocardial oxygen consumptions. Amgen and Cytokinetics are thus collaborating to develop Omecamtiv Mecarbil to treat heart failure with funding and strategic support from Servier. It is the main candidate for two large Phase 3 clinical trials GALACTIC-HF) Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) and METEORIC-HF. The three companies in collaboration are conducting both these trials. METEORIC-HF is a Phase 3 double-blinded, placebo-controlled, multicenter, parallel group clinical trial that aims at understanding the effects of Omecamtiv Mecarbil when compared to placebo on exercise capacity as determined by CPET (Cardio Pulmonary Exercise Testing) after 20 weeks of treatment. The trial will enroll 270 patients with HFrEF at sites in Europe, Canada and the U.S. To be eligible for enrollment, the patients must be a part of the New York Heart Association (NYHA) heart failure class II or III or have reduced exercise capacity when compared to age controls and must have a Left Ventricular Ejection Fraction (LVEF) ≤ 35 percent. The starting dose will be 25 mg twice daily and titrated to 25, 37.5 or 50 mg twice daily based on the same PK-guides dosing as used in the GALACTIC-HF. They will be randomized in a 2:1 fashion to Omecamtiv Mecarbil. A change in the peak oxygen uptake (pVO2) or CPET from baseline to Week 20, will be the primary endpoint.  A change in the total workload during CPET from baseline to week 20 and the change in the average daily activity units measured over 2 weeks from baseline to week 18-20 by accelerometry, will be the second endpoint.

The Facts About Heart Disease

From Visually.

 

“The start of this second Phase 3 clinical trial marks an important milestone in the expansion of our clinical trials program for Omecamtiv Mecarbil, testing the hypothesis that improving cardiac function with a drug candidate that directly increases myocardial contractility may improve exercise capacity,” said Fady I. Malik, M.D., Ph.D., executive vice president of Research & Development at Cytokinetics. “Exercise intolerance, typically manifested by shortness of breath and fatigue on exertion, is a predominant symptom of chronic heart failure and often the first symptom that prompts patients to seek medical care. If positive, this clinical trial may provide key clinically relevant evidence.”

 

Eli Lilly and Pfizer announce the results from the Phase 3 study of Tanezumab in chronic low back pain.


Eli Lilly and Pfizer recently announced positive results from a Phase 3 trial targeted at evaluating tanezumab in patients with chronic low back pain or CLBP [7]. The drug met the primary endpoint with a 10 mg dosage, showing a statistically significant improvement in pain when compared to placebo, at the 16-week mark. The lower dose of 5 mg showed improvement in pain but was not statistically significant when compared to placebo at the end 16 weeks.

33 million Americans are affected by the chronic low back pain that lasts for more than three months and can further lead to disability. Around 8 million of such patients suffer from CLBP that ranges from moderate to severe in intensity which hinders day to day activities. Currently, there is an unmet need for treatment of CLBP and limited options are available because the reason behind it is not yet known. Tanezumab is a monoclonal antibody under investigation that functions by selectively targeting and binding to NGF thus inhibiting its activities. NGF level increase is a manifestation of injury, inflammation or chronic pain. Tanezumab is expected to work by preventing the pain signals from reaching the muscles and spinal cord and is achieved by inhibiting NGF. A unique feature of tanezumab that makes it a good candidate is that its mechanism is novel and different from other drugs and NSAIDs and there is no report of addiction or abuse of the drug. Tanezumab is the first NGF inhibitor to receive a Fast Track designation from the FDA. A fast track designation is given to expedite the development process of therapies that have the potential to treat serious diseases and fulfill unmet needs. Upon final approval, tanezumab will be the first-in-class treatment for osteoarthritis pain and CLBP. The study was a placebo-and active-controlled, multicenter, randomized, double-blinded Phase 3 trial involving patients with moderate-to-severe CLBP. The aim of the study was to determine the safety and efficacy of the subcutaneous administration of tanezumab for a period of 16 weeks and oral tramadol prolonged release (PR) for 56 weeks and compare it to placebo. For this study, the patients enrolled were suffering from moderate-to-severe pain and did not experience pain relief or were intolerant to treatment with at least three different classes of analgesics. These patients had CLBP for 10 years on an average and reported a loss of ability and activity in their daily lives. 1832 patients randomly received one of the four treatments in a 2:2:2:3 ratio. One of the groups received placebo every eight weeks till week 16. At the stage of week 16, those that achieved the efficacy responder criteria were shifted equally to either tanezumab 5 mg or tanezumab 10 mg every eight weeks till week 56. The second group received the 5 mg every eight week till week 56, the third group received 10 mg and the fourth one received oral tramadol PR daily till week 56. The primary endpoint looked at the change in the daily average low back pain intensity (LBPI) score from baseline to week 16 for tanezumab vs. placebo. The secondary endpoint determined the efficacy between 16 and 56 weeks. The long-term safety of the drug through 80 weeks was also determined.

Back Pain 101

by ZocDoc.

From Visually.

 

“This study demonstrates the potential of tanezumab to treat individuals suffering from moderate-to-severe chronic low back pain who have been unable to achieve relief with currently available medicines,” said Ken Verburg, tanezumab development team leader, Pfizer Global Product Development. “This is one of the longest studies conducted to date in chronic low back pain. We look forward to further analyzing these results and believe the data from this study will support our planned future global regulatory submissions in chronic low back pain.” “Many patients living with chronic low back pain suffer from constant pain, which significantly impacts their ability to perform everyday tasks. Lilly and Pfizer recognize the unmet needs for those living with this life-altering and debilitating condition and continue to advance tanezumab as an innovative non-opioid treatment for these patients,” said Christi Shaw, president, Lilly Bio-Medicines.

 

Novartis strikes up a deal to venture into transformational therapy to reduce cardiovascular diseases.


Novartis recently announced that it would pay $150 million and obtain the rights to develop and commercialize TQJ230 from Akcea Therapeutics, an affiliate of Ionis Pharmaceuticals, for targeted cardiovascular therapy [8][9]. TQJ230 is an investigational subject which was previously known as AKCEA-APO(a)-LRx. It was first discovered by Ionis and was later co-developed by Akcea and Ionis. After this deal, Novartis will be responsible for the global development and marketing of the product. TQJ230 is a clinical stage drug that intends to treat patients with unusually high levels of lipoprotein (a known to increase the risk for cardiovascular diseases.

Lipoprotein (a) is a protein present in the blood, elevated levels of which collect in the arteries, leading to the narrowing of the arteries. Due to the constricted movement, there is reduced blood flow to kidneys, heart, brain and legs. It could eventually lead to atherosclerosis, thrombosis, coronary heart disease and stroke. A large number of people are affected by the elevated levels of Lp(a) and are thus at a higher risk of developing cardiovascular diseases. Diet alone is not an effective way of reducing the level of Lp(a) and there are no known treatments available for the same. In November 2018, results from a Phase 2 clinical trial showed a significant reduction in the levels of Lp(a) and pre-existing cardiovascular diseases in patients treated with TQJ230. The plan is to further a Phase 3 cardiovascular trial to look at the effectiveness of the treatment to fulfill the unmet needs of the patients. It will be executed and completed by Novartis as per the deal.

“No treatments are currently available to substantially lower Lp(a). People with this inherited risk factor are facing cardiovascular risks that cannot be addressed effectively with lifestyle changes,” said John Tsai, Head of Global Drug Development and Chief Medical Officer at Novartis. “We’re excited about the novel, RNA-targeting approach that could be a game-changer for people with elevated Lp(a). If our Phase 3 trial succeeds, we expect that TQJ230 will become the leading treatment option and another pillar of our longstanding commitment to re-imagining cardiovascular medicine.”

 

 

References:

  1. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm631412.htm.
  2. https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-egaten-treatment-fascioliasis-neglected-tropical-disease.
  3. https://www.fda.gov/Drugs/DrugSafety/ucm631182.htm?utm_campaign=CDER%20New%2002%2F22%2F2019&.
  4. https://www.fda.gov/downloads/forconsumers/consumerupdates/ucm107976.pdf.
  5. https://www.jnj.com/fda-advisory-committee-recommends-approval-of-spravatotm-esketamine-nasal-spray-ciii-for-adults-with-treatment-resistant-depression.
  6. https://www.amgen.com/media/news-releases/2019/02/amgen-cytokinetics-and-servier-announce-start-of-meteorichf-the-second-phase-3-clinical-trial-of-omecamtiv-mecarbil-in-patients-with-heart-failure/.
  7. https://www.pfizer.com/news/press-release/press-release-detail/pfizer_and_lilly_announce_top_line_results_from_phase_3_study_of_tanezumab_in_chronic_low_back_pain.
  8. https://www.novartis.com/news/media-releases/novartis-pursue-transformational-therapy-reduce-risk-cardiovascular-disease-people-living-elevated-levels-inherited-lipoproteina.
  9. https://xconomy.com/san-diego/2019/02/25/novartis-to-pay-150m-to-ionis-akcea-for-drug-to-slow-heart-disease/?mc_cid=4585bcd05c&mc_eid=7420647896.

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. Currently, he is a Lead Scientist at MicroCures Inc. Previously, he served as 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 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.

Image Sources: Wikipedia and Twitter

Cover image: “Mouse hind limb tibialis anterior (TA) muscles were injected with BaCl2 followed by daily systemic administration of rapamycin (Rap) starting 7 days after injury. The animals were sacrificed at different days, and the injured muscles were dissected and cryosectioned followed by hematoxylin (blue) and eosin (pink to red) staining. This image shows the regeneration of muscle tissue seven days after the injury, but before the systematic administration of Rap. The regenerated muscle fibers, stained by eosin and showed as red patches, were formed but not fully matured. Nuclei were stained by hematoxylin in blue. This image corresponds to Fig 10B from JCB 189: 1157-1169, 2010. See also CIL: 13595, 13597, 13598, 13599, and 13600.” Source

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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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