FDA grants breakthrough device designation to artificial intelligence software for CTEPH pattern recognition from Bayer and MSD

FDA grants breakthrough device designation to artificial intelligence software for CTEPH pattern recognition from Bayer and MSD


BayerBayer announced today that the U.S. Food and Drug Administration (FDA) granted Breakthrough Device Designation to the Artificial Intelligence Software for Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Pattern Recognition, which Bayer is currently developing jointly with MSD (tradename of Merck & Co., Inc., Kenilworth, N.J., USA).

A rare form of pulmonary hypertension, CTEPH affects an estimated 8 to 40 people per million globally. CTEPH can be difficult to diagnose because its symptoms are similar to those of other lung diseases. Being a rare disease, physicians may not always recognize CTEPH due to factors including a lack of clinical awareness and complex findings involving the heart, lung and pulmonary vessels. Computed tomography pulmonary angiography (CTPA) as well as a ventilation/perfusion scan (V/Q scan) are common diagnostic modalities to detect CTEPH. Radiologists may have the first opportunity to identify CTEPH in patients; therefore it is vital that they recognize CTEPH indicators on CTPA images.

Development of the software will rely on using deep learning methodology to support radiologists by identifying signs of CTEPH in CTPA scans. The software processes image findings of cardiovascular, lung perfusion and pulmonary vessel analyses in combination with the patient’s history of pulmonary embolism. If the development is successful, the software could be deployed via Bayer’s Radimetrics™, an informatics technology platform that connects contrast medium with injector and scan information to provide important insights.

“Bayer is looking forward to leveraging our expertise in Radiology to develop a software to support radiologists and treating physicians in the complex diagnostic decision making process of this rare disease,” said Prof. Dr. Olaf Weber, Head of Radiology Research & Development of Bayer AG’s Pharmaceuticals Division. “We hope that greater awareness of CTEPH in conjunction with a decision-support tool will eventually assist in diagnosing patients earlier and more reliably, thereby allowing earlier treatment.”

The FDA Breakthrough Device Program is intended to help patients have more timely access to devices and breakthrough technologies that provide for more effective treatment or diagnosis for life-threatening or irreversibly debilitating diseases by expediting their development, assessment, and review. While the FDA Breakthrough Device Designation is expected to expedite the software’s assessment and review, its development remains complex given the nature of the disease and technology.

About Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

CTEPH is a progressive type of pulmonary hypertension, in which it is believed that thromboembolic occlusion (organized blood clots) of pulmonary vessels gradually builds up and subsequently leads to an increased blood pressure in the pulmonary arteries, resulting in an overload of the right heart. CTEPH may evolve after prior episodes of acute pulmonary embolism (PE). The standard and potentially curative treatment for CTEPH is pulmonary thromboendarterectomy (PTE), a surgical procedure in which the blood vessels of the lungs are cleared of clot and scar material. However, a considerable number of patients with CTEPH (20%-40%) are not operable and in up to 35 percent of patients, the disease persists or reoccurs after PTE.

As many as 1 out of every 25 people who had a PE (even if they were treated with at least 3 months of anticoagulants) could go on to develop CTEPH. Symptoms of CTEPH include shortness of breath, edema, fatigue, and chest pain and are therefore similar to other, more common diseases, resulting in an often delayed diagnosis of CTEPH.

Bayer and MSD are in a worldwide collaboration in the field of sGC modulators with the goal to fully evaluate this therapeutic class in areas of unmet medical need.

About Bayer’s Radimetrics™

Bayer’s Radimetrics™ intelligently connects contrast, injector and scan information into a Seamlessly Smart™ solution to provide critical insights to radiology teams. This helps deliver more personalized care and achieve reproducible quality, in line with radiation standards and regulation. As a true multi-modality solution, spanning Magnetic Resonance Imaging (MRI), Computed Tomography (CT), Nuclear Medicine (NM), X-ray, ultrasound and mammography, it helps radiology departments and practices generate diagnostic quality images more safely, consistently and efficiently. Radimetrics seamlessly integrates with the existing IT infrastructure and radiology equipment through respective interfaces.

About Bayer

Bayer is a global enterprise with core competencies in the Life Science fields of health care and agriculture. Its products and services are designed to benefit people and improve their quality of life. At the same time, the Group aims to create value through innovation, growth and high earning power. Bayer is committed to the principles of sustainable development and to its social and ethical responsibilities as a corporate citizen. In fiscal 2017, the Group employed around 99,800 people and had sales of EUR 35.0 billion. Capital expenditures amounted to EUR 2.4 billion, R&D expenses to EUR 4.5 billion.

About MSD

For more than a century, MSD, a leading global biopharmaceutical company, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases. MSD is a trade name of Merck & Co., Inc., with headquarters in Kenilworth, N.J., U.S.A. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. Today, MSD continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world – including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases including HIV and Ebola.

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Eli Lilly and Company

Lilly submits New Drug Application to the FDA for lasmiditan for acute treatment of migraine, receives Breakthrough Therapy Designation for Emgality™ (galcanezumab-gnlm) for prevention of episodic cluster headache


Eli Lilly and CompanyEli Lilly and Company (NYSE: LLY) has announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for lasmiditan for the acute treatment of migraine with or without aura in adults. Lasmiditan is an investigational, oral, centrally-penetrant, selective serotonin 5-HT1F agonist that is structurally and mechanistically distinct from other approved migraine therapies and lacks vasoconstrictive activity. It is the first and only molecule in the “-ditan” class under evaluation for the acute treatment of migraine in adults. If approved, it could represent the first significant innovation for the acute treatment of migraine in more than two decades.

Lilly also plans to submit an sBLA to the FDA for Emgality for the preventive treatment of episodic cluster headache in adults by the end of the year. The FDA has granted Breakthrough Therapy Designation to Emgality for episodic cluster headache. Breakthrough Therapy Designation is a process that is intended to expedite the development and review of drugs that treat serious or life-threatening diseases and, based on preliminary clinical evidence, may demonstrate substantial improvement over available therapies. Currently, there are no approved preventive treatments for episodic cluster headache in the U.S.

“Headache disorders like migraine and cluster headache affect each person differently, and many patients spend years cycling through different medications to effectively diagnose and treat their symptoms,” said Gudarz Davar, M.D., vice president, Neurology Development, Lilly Bio-Medicines. “Lilly has spent the last 25 years researching innovative therapies to treat headache disorders, and we are thrilled to be one step closer to potentially providing new and different options with lasmiditan for the acute treatment of migraine and Emgality for the preventive treatment of episodic cluster headache.”

The NDA for lasmiditan includes data from two Phase 3 single-attack studies (SAMURAI and SPARTAN), which evaluated the safety and efficacy of lasmiditan for the acute treatment of migraine. In both studies, at two hours following the first dose of lasmiditan, the percentage of patients who were migraine pain-free was significantly greater compared to placebo. These results were significant across all studied doses. Lasmiditan also met the key secondary endpoint, with a significantly greater percentage of patients free of their most bothersome symptom (MBS) compared with placebo at two hours following the first dose. In these studies, patients chose their MBS from sensitivity to light, sensitivity to sound or nausea. The most commonly reported adverse events after lasmiditan dosing were dizziness, paresthesia, somnolence, fatigue, nausea, muscle weakness and numbness. Data from these studies were presented at the American Headache Society (AHS) annual meeting and the American Academy of Neurology (AAN) annual meeting.

“As a caregiver for someone living with chronic migraine, I know firsthand how disabling headache diseases can be,” said Kevin Lenaburg, executive director of the Coalition For Headache And Migraine Patients (CHAMP). “We’re excited about the new innovations in the acute treatment of migraine and the preventive treatment of migraine and episodic cluster headache, and we’re thankful for Lilly’s commitment to continue to investigate and hopefully bring these important new therapeutic options to market.”

Lasmiditan and Emgality represent two of three treatments in Lilly’s pain portfolio. Emgality was approved by the FDA in September 2018 for the preventive treatment of migraine in adults. The portfolio also includes tanezumab, developed in partnership with Pfizer, which is currently being investigated for the treatment of osteoarthritis pain, chronic low back pain and cancer pain.

Please see Full Prescribing Information, including Patient Information, for Emgality. See Instructions for Use included with the pen and prefilled syringe.

About Migraine

Migraine is a disabling, neurologic disease characterized by recurrent episodes of severe headache accompanied by other symptoms including nausea, vomiting, sensitivity to light and sound, and changes in vision.(1,2) More than 30 million American adults have migraine, with three times more women affected by migraine compared to men.(3,4,5,6) According to the Medical Expenditures Panel Survey, the total unadjusted cost associated with migraine in the U.S. is estimated to be as high as $56 billion annually, yet migraine remains under-recognized and under-treated.(3,7,8)

About Cluster Headache

Cluster headache is a disabling primary headache disorder composed of recurrent “attacks” of intense headaches on one side of the head, frequently associated with pain behind or around one eye, restlessness and agitation.(9,10) Cluster headache attacks typically last between 15 to 180 minutes, occurring near daily to multiple times daily during a cluster period.(9) It is estimated that 85 to 90 percent of cluster headache cases are classified as “episodic,” while the remaining 10 to 15 percent are classified as “chronic.” Diagnostically, episodic cluster headache and chronic cluster headache are differentiated based on the duration of remission periods.(9)

About Lasmiditan

Lasmiditan is an investigational, first-in-class molecule under evaluation for the acute treatment of migraine. Lasmiditan uses a novel mechanism of action which selectively targets 5-HT1F receptors, including those expressed in the trigeminal pathway, and has been designed for the acute treatment of migraine without the vasoconstrictor activity associated with some migraine therapies. Data from two Phase 3 single-attack studies (SAMURAI and SPARTAN) have been presented at the American Headache Society (AHS) annual meeting and the American Academy of Neurology (AAN) annual meeting. In March 2017, Lilly completed the acquisition of CoLucid Pharmaceuticals, including lasmiditan, which was originally discovered at Lilly.

About Emgality

Emgality is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) and blocks its binding to the receptor. Emgality offers a once-monthly, self-administered, subcutaneous injection.

About Lilly’s Commitment to Headache Disorders

For over 25 years, Lilly has been committed to helping people suffering from headache disorders, investigating more than a dozen different compounds for the treatment of migraine, cluster headache and other disabling headache disorders. These research programs have accelerated the understanding of these diseases and furthered the advancement of Lilly’s comprehensive late-stage development programs studying galcanezumab-gnlm for prevention of migraine and cluster headache, and lasmiditan for the acute treatment of migraine. Our goal is to make life better for people with headache disorders by offering comprehensive solutions to prevent or stop these disabling diseases. The combined clinical, academic and professional experience of our experts helps us to build our research portfolio, identify challenges for healthcare providers and pinpoint the needs of patients living with migraine and cluster headache.

About Eli Lilly and Company

Lilly is a global healthcare leader that unites caring with discovery to make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism.

1. Katsarava Z, Buse D, Manack A, et al. Defining the differences between episodic migraine and chronic migraine. Current Pain Headache Reports. 2012;16:86.

2. Blumenfeld AM, Varon SF, Wilcox TK, et al. Disability, HRQOL, and resource use amongst chronic and episodic migraineurs. Results from the International Burden of Migraine Study (IBMS). Cephalalgia. 2011;31:301.

3. Lipton RB, Bigal ME, Diamond M, et al. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68:343-349.

4. Data on File. Lilly USA, LLC. DOF-GZ-US-0028.

5. US Census Bureau. Quick Facts. https://www.census.gov/quickfacts/fact/table/US/PST045217 . Updated September 23, 2018. Last accessed November 1, 2018.

6. Migraine: Symptoms and causes. Mayo Clinic. https://www.mayoclinic.org/diseasesconditions/migraine-headache/symptoms-causes/syc-20360201. Updated May 31, 2018. Last accessed November 1, 2018.

7. Raval AD, Shah A. National trends in direct health care expenditures among US adults with migraine: 2004 to 2013. Journal of Pain. 2017;18:96-107.

8. Diamond, S, Bigal ME, Silberstein S. Patterns of diagnosis and acute and preventive treatment for migraine in the United States: results from the American Migraine Prevalence and Prevention Study. Headache. 2007;47:355-363.

9. Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edition. Cephalalgia. 2018;38(1):1-211.

10. Matharu M, Goadsby P. Trigeminal autonomic cephalgias. Journal of Neurology, Neurosurgery, and Psychiatry. 2002;72(Suppl II):ii19-ii26.

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Breakthrough neurotechnology for treating paralysis


Three paraplegics who sustained cervical spinal cord injuries many years ago are now able to walk with the aid of crutches or a walker thanks to new rehabilitation protocols that combine targeted electrical stimulation of the lumbar spinal cord and weight-assisted therapy. This latest study, called STIMO (STImulation Movement Overground), establishes a new therapeutic framework to improve recovery from spinal cord injury. All patients involved in the study recovered voluntary control of leg muscles that had been paralyzed for many years. Unlike the findings of two independent studies published recently in the United States on a similar concept, neurological function was shown to persist beyond training sessions even when the electrical stimulation was turned off. The STIMO study, led by the Ecole Polytechnique Fédérale de Lausanne (EPFL) and the Lausanne University Hospital (CHUV) in Switzerland, is published in the 1 November 2018 issues of Nature and Nature Neuroscience.

“Our findings are based on a deep understanding of the underlying mechanisms which we gained through years of research on animal models. We were thus able to mimic in real time how the brain naturally activates the spinal cord,” says EPFL neuroscientist Grégoire Courtine.

“All the patients could walk using body weight support within one week. I knew immediately that we were on the right path,” adds CHUV neurosurgeon Jocelyne Bloch, who surgically placed the implants in the patients.

“The exact timing and location of the electrical stimulation are crucial to a patient’s ability to produce an intended movement. It is also this spatiotemporal coincidence that triggers the growth of new nerve connections,” says Courtine.

This study achieves an unprecedented level of precision in electrically stimulating spinal cords. “The targeted stimulation must be as precise as a Swiss watch. In our method, we implant an array of electrodes over the spinal cord which allows us to target individual muscle groups in the legs,” explains Bloch. “Selected configurations of electrodes are activating specific regions of the spinal cord, mimicking the signals that the brain would deliver to produce walking.”

The challenge for the patients was to learn how to coordinate their brains’ intention to walk with the targeted electrical stimulation. But that did not take long. “All three study participants were able to walk with body-weight support after only one week of calibration, and voluntary muscle control improved tremendously within five months of training”, says Courtine. “The human nervous system responded even more profoundly to the treatment than we expected.”

Helping the brain help itself

The new rehabilitation protocols based on this targeted neurotechnology lead to improved neurological function by allowing the participants to actively train natural overground walking capabilities in the lab for extensive periods of time, as opposed to passive training like exoskeleton-assisted stepping.

During rehabilitation sessions, the three participants were able to walk hands-free over more than one kilometer with the help of targeted electrical stimulation and an intelligent bodyweight-support system. Moreover, they exhibited no leg-muscle fatigue, and so there was no deterioration in stepping quality. These longer, high-intensity training sessions proved crucial for triggering activity-dependent plasticity – the nervous system’s intrinsic ability to reorganize nerve fibers – which leads to improved motor function even when the electrical stimulation is turned off.

Previous studies using more empirical approaches, such as continuous electrical stimulation protocols, have shown that a select few paraplegics can indeed take steps with the help of walking aids and electrical stimulation, but only over short distances and as long as the stimulation is on. As soon as the stimulation is turned off, the patients immediately return to their previous state of paralysis and are no longer able to activate leg movements.

Next steps

The startup GTX medical, co-founded by Courtine and Bloch, will use these findings to develop tailored neurotechnology with the aim to turn this rehabilitation paradigm into a treatment available at hospitals and clinics everywhere. “We are building next-generation neurotechnology that will also be tested very early post-injury, when the potential for recovery is high and the neuromuscular system has not yet undergone the atrophy that follows chronic paralysis. Our goal is to develop a widely accessible treatment,” adds Courtine.

Fabien B Wagner, Jean-Baptiste Mignardot, Camille G Le Goff-Mignardot, Robin Demesmaeker, Salif Komi, Marco Capogrosso, Andreas Rowald, Ismael Seáñez, Miroslav Caban, Elvira Pirondini, Molywan Vat, Laura A McCracken, Roman Heimgartner, Isabelle Fodor, Anne Watrin, Perrine Seguin, Edoardo Paoles, Katrien Van Den Keybus, Grégoire Eberle, Brigitte Schurch, Etienne Pralong, Fabio Becce, John Prior, Nicholas Buse, Rik Buschman, Esra Neufeld, Niels Kuster, Stefano Carda, Joachim von Zitzewitz, Vincent Delattre, Tim Denison, Hendrik Lambert, Karen Minassian, Jocelyne Bloch, Grégoire Courtine.

Targeted neurotechnology restores walking in humans with spinal cord injury.

Nature, volume 563, pages 65-71 (2018). doi: 10.1038/s41586-018-0649-2.

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