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MedNess: bite-size biopharma and medtech news

23rd September, 2020
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Onco I-Analyse
Mirati and BI announce clinical collaboration for KRAS inhibitors
On 17th September, Mirati Therapeutics and Boehringer Ingelheim announced clinical collaboration to evaluate orally available small molecules, MRTX849, a KRAS G12C selective inhibitor in combination with BI 1701963, a SOS1::pan-KRAS inhibitor across a range of solid tumors harbouring the KRAS G12C mutation. While MRTX849 is selective for G12C substitution mutation, BI 1701963 blocks KRAS independent of mutation type. The collaboration will focus on providing clinical benefit to patients with lung and colorectal cancers, who currently have limited treatment options.
KRAS has remained a difficult therapeutic target for many decades and tumors harbouring KRAS mutations are associated with poor prognosis. Apart from efficacy, targeting KRAS also involves considerable safety issues. KRAS G12C mutations are present in ~14% of NSCLC adenocarcinoma, 3-4% of CRC and in subsets of various other tumors.
The proposed combination has shown synergistic anti-tumour activity of KRAS G12C and SOS1 inhibition in preclinical studies based on the complementary mechanisms of these targeted oncology agents. BI 1701963 targets and binds to SOS1, which regulates the KRAS GDP-GTP cycle and promotes nucleotide exchange for the formation of KRAS-GTP, the activated/ON state of KRAS. Thus, BI 1701963 prevents the formation of KRAS(ON) state and shifts the equilibrium towards the KRAS(OFF) state exposing KRAS G12C mutant tumors to KRAS G12C inhibitors, like MRTX849 that covalently bind  to cytosine 12 within the switch II pocket of GDP-KRAS G12C (KRAS(OFF)). This prevents the activation of downstream RAF/MEK/ERK signalling pathway by GTP-KRAS.
Both companies have a comprehensive KRAS program and several ongoing trials either as monotherapy or in combination with other agents across solid tumors. Mirati also anticipates enrolment completion in the phase 1/2 registrational KRYSTAL study in 2L+ NSCLC. Amgen is a key rival to Mirati as it is also conducting a phase 2 registrational study for its KRAS G12C inhibitor, AMG-510, in NSCLC. AMG-510, however, has not shown encouraging results outside of NSCLC.
Under the collaboration, Mirati will sponsor clinical trials while both BI and Mirati will share the costs and oversee clinical development for the combination therapy.
Collated by :Shilpa Rawal, PhD
COVID Special
AstraZeneca resumes clinical trials of the COVID-19 vaccine AZD1222 after a brief pause
AstraZeneca resumes the clinical trial for its COVID-19 vaccine AZD1222 in collaboration with Oxford. It was temporarily paused for a couple of days following an adverse event involved in the UK Phase III vaccine trial. The trial was paused as a part of a standard review process which is a natural outcome whenever an unexplained illness occurs in a clinical trial.
Pascal Soriot, Chief Executive Officer, said: “At AstraZeneca we put science, safety and the interests of society at the heart of our work. This temporary pause is living proof that we follow those principles while a single event at one of our trial sites is assessed by a committee of independent experts. We will be guided by this committee as to when the trials could restart, so that we can continue our work at the earliest opportunity to provide this vaccine broadly, equitably and at no profit during this pandemic.”
Combination of Barcitinib and Remdesivir reduces the time to recovery in hospitalized COVID-19 patients
Initial data from the Adaptive COVID-19 Treatment Trial (ACTT-2) shows that barcitinib in combination with remdesivir, reduces the time to recovery in hospitalized COVID-19 patients in comparison to when only remdesivir is given. This was the primary endpoint for the ACTT-2 trial which was carried out by Eli Lilly and Company and Incyte and was sponsored by NIAID.
The ACTT-2 trial showed that there was a statistically significant one-day reduction in the median recovery time for the overall patient population who were treated by the combination therapy rather than by remdesivir alone.
"We are pleased with these data from the ACTT-2 study," said Patrik Jonsson, Lilly senior vice president and president of Lilly Bio-Medicines. "There is an urgent need to identify COVID-19 treatments, and we will continue to work with NIAID to understand these data and next steps on baricitinib's role moving forward. We appreciate NIAID selecting baricitinib for inclusion in this important study and the participants, investigators and collaborators for the vital roles they played." "As a company, we've moved quickly to develop and evaluate medicines for patients for the prevention and treatment of COVID-19," said Daniel Skovronsky, M.D., Ph.D., Lilly senior vice president and chief scientific officer. "These data allow us to better understand baricitinib's role in potentially improving outcomes for hospitalized COVID-19 patients, and we look forward to continuing this research alongside our other initiatives to combat COVID-19."
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Regulatory News
FDA grants Fast Track designation for Rhenium NanoLiposomes (RNL™) for the treatment of rGBM patients
“Fast Track designation validates the potential importance of this novel radiotherapeutic for patients with recurrent glioblastoma who currently have no good treatment options,” said Dr. Marc Hedrick, President and Chief Executive Officer of Plus Therapeutics. “With this designation in hand, we intend to move into Cohort 6 of the trial, one key step closer to bringing forth a novel therapy for these patients.”
CHMP recommends EU approval of Tecentriq® (atezolizumab) + Avastin® (bevacizumab) for the treatment of adult patients with advanced or unresectable HCC who have not received prior systemic therapy
“Today’s recommendation by the CHMP is a major step towards bringing Tecentriq in combination with Avastin to people in Europe who suffer from advanced or unresectable hepatocellular carcinoma,” said Levi Garraway, M.D., Ph.D., Chief Medical Officer and Head of Global Product Development. “This represents an important milestone in a deadly malignancy and is part of our long-term commitment to improve the lives of people with various types and stages of liver disease.”
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Trial Results
Final OS Data announced from Ph 3 ClarIDHy Study of TIBSOVO® in Previously Treated IDH1-Mutant Cholangiocarcinoma Patients
“Advanced cholangiocarcinoma is a rapidly progressing, aggressive disease with a grim prognosis for patients,” said Chris Bowden, M.D., chief medical officer at Agios. “The data from the ClarIDHy Phase 3 study show that treatment with TIBSOVO® has the potential to lengthen time to disease progression and have a clinically meaningful impact on life expectancy for patients with IDH1-mutant cholangiocarcinoma. We will collaborate closely with regulators to advance this potential new oral, targeted treatment option for patients.”
PADCEV® (enfortumab vedotin-ejfv) Significantly Improved OS in Ph 3 Trial in Previously Treated Locally Advanced or Metastatic Urothelial Cancer
“These survival results from the confirmatory trial for PADCEV are welcome news for patients whose cancer has progressed after platinum-based chemotherapy and immunotherapy,” said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. “We continue to explore PADCEV’s activity across the spectrum of urothelial cancer including its potential for use in earlier lines of therapy.”
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Trial/Program Status
First Patient Dosed with Combination of INT230-6 and Yervoy® in a Ph 2 Study
“Bringing INT230-6 into phase 2 human testing in combination with Yervoy is an important achievement for Intensity Therapeutics,” commented Lewis H. Bender, President and Chief Executive Officer of Intensity Therapeutics. “Our preclinical and clinical data have resulted in favorable safety for INT230-6 as a single agent or in combination with immunotherapies.  The phase 1 escalation portion of our INT230-6 development program is complete.  We are excited about starting the phase 2 portion of our trial using INT230-6 at proper doses early in the treatment process especially in combination with Yervoy.”
Ph 2 Study of Patritumab Deruxtecan in HER3 Expressing Advanced CRC Patients Initiated
“The prognosis of patients with advanced or metastatic colorectal cancer remains poor, and there is a need to develop new treatment strategies, including targeting HER3,” said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. “In this study, we are exploring whether the targeted delivery of cytotoxic chemotherapy with patritumab deruxtecan to cancer cells with varying levels of HER3 expression may be a potential treatment option for previously treated advanced or metastatic colorectal cancer.”
Collated by : Richa Tewari, PhD
Medness Plus
Dupixent receives a Breakthrough Therapy Designation from the FDA for eosinophilic esophagitis 
FDA recently approved a Breakthrough Therapy Designation for eosinophilic esophagitis (EoE) to Sanofi and Regeneron for dupixent. Based on the positive results from Part A of a Phase 3 trial in patients with EoE, FDA granted the Breakthrough Therapy Designation for patients 12 years and older with EoE. A Breakthrough Therapy Designation is usually granted to expedite the development of drugs for life-threatening conditions. These treatments must show a clinically significant improvement over the available therapies or over placebo if no treatments are available.
In case of EoE, there are no FDA-approved medicines and proper medications are needed to provide relief from esophagus damage. The approval was based on results from the Part A of a pivotal Phase 3 trial that evaluated the efficacy of dupixent in 12 year and older patients with EoE. It was a randomized, double-blind, placebo-controlled study that met the co-primary endpoints and all key secondary endpoints. It involved 81 patients and those who were given a weekly dose of 300 mg of dupixent, experienced a reduction in esophageal inflammation and reduction in the overall symptoms. The safety and efficacy determined from Part A was similar to the those for the approved indications for dupixent. The EoE trial is still going on with an additional part B and patients who complete part A and B may continue to a 28-week extended active treatment period, Part C.
AstraZeneca’s Fasenra, meets both co-primary endpoints in the Phase III trial for patients with chronic rhinosinusitis with nasal polyps
Fasenra (benralizumab) met both co-primary endpoints in the OSTRO Phase III trial for patients with chronic rhinosinusitis with nasal polyps (CRSwNP). The drug showed a significant improvement in the nasal polyp size and also in the blockage of nasal passage in patients with CRSwNP. The safety profile for the study was similar to that for known profile of Fasenra. Fasenra has been approved as an add-on maintenance therapy for severe eosinophilic asthma.
Professor Claus Bachert, Head of the Department of Oto-Rhino-Laryngology and Chair of the Upper Airway Research Laboratory, University Hospital Ghent, Belgium, the principal investigator of the trial, said: “Chronic rhinosinusitis with nasal polyps is difficult to treat and the underlying drivers and natural history of the disease are not fully established. The OSTRO results show that Fasenra’s eosinophil-depleting mechanism of action may benefit patients with this often-debilitating condition.” Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “Patients with chronic rhinosinusitis with nasal polyps suffer significantly with nasal congestion and a reduced quality of life. Current treatments, such as intranasal or oral corticosteroids and surgery to remove polyps, do not fully address patient needs. The OSTRO data indicate Fasenra can benefit patients with nasal polyps. We look forward to completing the full analysis and sharing these results at an upcoming medical meeting.”
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Medness Reviews
Tandem’s artificial pancreas Control-IQ helps young type 1 diabetes patients
Type 1 diabetes or juvenile diabetes is a condition in which the pancreas does not produce insulin, which is responsible for the entry of blood glucose into the cells. Patients with type 1 diabetes usually monitor their blood sugar level continuously to know when to administer insulin in their body. The traditional way of insulin intake is multiple injections every day. Tandem’s Control-iQ or artificial pancreas is a next-generation hybrid closed-loop insulin delivery system that monitors the patient’s blood glucose level and adjusts the dosage of insulin automatically. Recently published article from the New England Journal of Medicine showed that the artificial pancreas has been effectively delivered insulin in patients under 14 years of age. Also, the blood glucose level was in the target range for a greater percentage of the time. There were no significant reported side effects of the study. Moreover, Contro-IQ has earned approval from the U.S. Food and drug administration to use its young patients.
Promising study demonstrates short-term learning impairment occurs before the memory deficit in preclinical Alzheimer’s disease
 Amyloid beta (Aβ) plaque accumulates in the brain two decades before the cognitive dysfunction of Alzheimer’s disease (AD) emerges. Dementia or memory loss progresses over a longer period and also varies between patients. Patients are considered preclinical AD while they do not exhibit cognitive impairment or dementia yet their Aβ level is abnormal. Clinical trials of AD drugs fail to assess the efficacy because of this long timeline. 
This Australian study utilized the Online Repeated Cognitive Assessment Language Learning Test (ORCA-LLT), in which participants (Aβ+ or Aβ-) were taught the meaning of 50 Chinese characters. In this home-based ORCA training, participants had to decide whether the Chinese character matches an English word. The result shows that Aβ+ participants were not as efficient as Aβ- during the six days of the acquisition phase of the task. Moreover, the observed deficits in Aβ+ subjects correlated with increased ventricular size and reduced hippocampi, suggesting less gray-matter volume. Interestingly, performance on the task did not correlate with either measure in Aβ–subjects. ORCA-LLT paradigm successfully reveals the inability of acquiring novel information by preclinical AD patients while their memory performance was normal. ORCA-LLT, being scalable and easy to apply in a larger cohort could become a great tool for a longitudinal clinical study.
Collated by : Rinki Saha
Conference Coverage
Click here for top 50+ abstracts presented @ ESMO 2020
Medness Business
Onco-News

Vaccinex Announces Clinical Collaboration with Merck to Evaluate Pepinemab + KEYTRUDA® in Advanced, Recurrent or mSCCHN
“We are pleased to be working with Merck to evaluate the potential of pepinemab in combination with KEYTRUDA® to further improve the efficacy of cancer immunotherapy,” said Maurice Zauderer, Ph.D., President and Chief Executive Officer of Vaccinex. “Several prior studies suggest that inhibition of SEMA4D increases immune infiltration and alters the balance of cytotoxic and immunosuppressive cells in the tumor microenvironment. SEMA4D is highly expressed in HNSCC and is believed to promote correspondingly high levels of myeloid derived suppressor cells. This collaboration provides an opportunity to evaluate this innovative approach in combination with anti-PD-1 therapy.” 

 

Foundation Medicine and Takeda Announce Collaboration To Develop FoundationOne®CDx and FoundationOne®Liquid CDx as Companion Diagnostics for Takeda’s Late-Stage Lung Cancer Portfolio
“Our collaboration with Foundation Medicine will address an urgent need for broad access to genomic tests, ultimately expanding treatment options and potentially improving outcomes for people with ALK+ and EGFR Exon20 insertion+ mNSCLC,” said Christopher Arendt, Head, Oncology Therapeutic Area Unit, Takeda. “Robust, accurate and timely testing is crucial to enable oncologists to make informed treatment decisions so that advanced cancer patients receive the optimal therapy for their disease.”
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Collated by : Richa Tewari, PhD
Editors' Desk
Richa Tewari, PhD
Oncology News
Esha Sehanobish, PhD
MedNess Plus
Arundithi Ananthanarayanan
MedNess Reviews
Divyaanka Iyer
BioPharma News
Shilpa Rawal, PhD
Onco I-Analyse
Debarati Banik
HealthIT
Rinki Saha
BioPharma News
Abhi Dey
Consulting Editor
Nisha Peter, PhD
Managing Editor
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The sponsors do not have any influence on the nature or kind of the news/analysis reported in MedNess. The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of Medness. 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 Medness. This blog is strictly for news and information. It does not provide medical advice, diagnosis or treatment nor investment suggestions. 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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Content Editors: Richa Tewari , Esha Sehanobish , Rinki Saha , Arundithi Ananthanarayanan , Divyaanka Iyer , Shilpa Rawal, PhD ,  Debarati Banik
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