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3rd November, 2020
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Onco I-Analyse
AstraZeneca and Daiichi Sankyo’s Enhertu granted Priority Review by the US FDA
On 28th October, the US FDA accepted the sBLA and granted priority review for Enhertu (trastuzumab deruxtecan), a HER2-directed ADC for patients with HER2+ metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. The PDUFA action date has been set for Q1 2021.
The application is based on the Ph 2 DESTINY-Gastric01 study evaluating Enhertu against physicians’ choice chemotherapy (paclitaxel or irinotecan monotherapy) in Japanese and Korean patients progressing on at least two prior regimens including trastuzumab.
The trial demonstrated a statistically significant and clinically meaningful improvements versus chemotherapy in the primary endpoint of ORR (ORR: 51% vs. 14%, P<0.001) and key secondary endpoint of OS (mOS: 12.5 vs. 8.4 months, P=0.01). The safety profile was consistent with Phase I trial.
Earlier in May, Enhertu was granted the breakthrough therapy designation by the US FDA for HER2+, unresectable or metastatic gastric or GEJ adenocarcinoma with two or more prior regimens including trastuzumab. In September 2020, Enhertu was approved by the Japanese MHLW for the same patient segment after having received the SAKIGAKE designation in March 2018.
Gastric cancer is an aggressive cancer with particularly high incidence rates in Japan and Korea and is the third leading cause of cancer-related deaths in the world. In the US, ~20% gastric tumors have HER2 overexpression and even poorer prognosis than the ones without HER2 overexpression.
Currently, there are no HER2 targeted approved therapies beyond frontline treatment, with Trastuzumab based chemotherapy combination, for HER2+ metastatic gastric/GEJ adenocarcinoma. Ehnertu is the first and only HER2 targeted therapy to demonstrate significant survival benefit compared to chemotherapy in this patient segment, which remains an area of high unmet need. In 2015, Roche’s Kadcyla failed to show clinical benefit in similar patient population in a Phase II/III study.
Enhertu also showed clinical benefit in HER2 low-expressors which might extend its opportunity beyond HER2+ gastric cancer.
Collated by :Shilpa Rawal, PhD
COVID Special
FDA approves Remdesivir for the treatment of COVID-19
FDA recently approved remdesivir (Veklury) for the treatment of adults and younger patients 12 years and above weighing a minimum of around 88 pounds for the treatment of COVID-19 that requires hospitalization. It is the first treatment to be approved for COVID-19. It is an antiviral drug which has been approved to be administered in a healthcare setting or in an inpatient setting in the hospital. The application was granted a Priority review and a Fast Track designation along with a Material Threat Medical Countermeasure Priority Review Voucher.
“Since the beginning of the COVID-19 pandemic, Gilead has worked relentlessly to help find solutions to this global health crisis. It is incredible to be in the position today, less than one year since the earliest case reports of the disease now known as COVID-19, of having an FDA-approved treatment in the U.S. that is available for all appropriate patients in need,” said Daniel O’Day, Chairman and Chief Executive Officer, Gilead Sciences. “The speed and rigor with which Veklury has been developed and approved in the U.S. reflect the shared commitment of Gilead, government agencies and clinical trial investigators to advance well-tolerated, effective treatment options for the fight against COVID-19. We will continue to work at speed with the aim of enhancing patient outcomes with Veklury to ensure all patients with COVID-19 have the best chance at recovery.”
Johnson and Johnson prepare to resume the Phase 3 trial for Janssen’s COVID-19 vaccine 
Johnson and Johnson is presently preparing to resume its Phase 3 ENSEMBLE trial to determine the safety and efficacy of Janssen’s COVID-19 vaccine candidate. It was temporarily paused after a serious medical event was experienced by a study candidate. But after proper investigation of the reasons, no clear cause was identified by independent experts and the company had no indications that could indicate that the cause of the serious medical event was the vaccine. The independent Data Safety and Monitoring Board (DSMB) which is currently overseeing the ENSEMBLE trial after consultation with the FDA has suggested resuming the clinical trial. Globally, the discussions to begin the trial are now under progress along with the submission for the approval by the IRB. The company will continue to be blinded based on the protocol requirements. The Phase 3 ENSEMBLE trial is currently evaluating the safety and efficacy of a single dose of their candidate COVID-19 vaccine in up to 60000 adults over the age of 18 years. It is a randomized, placebo-controlled, double-blind trial which has a major representation of those above the age of 60 years.
Click here for more COVID news
Collated by : Esha Sehanobish, PhD
Drug/Diagnostics Approvals
European Commission and NMPA approve Tecentriq® + Avastin® for 1L advanced or unresectable HCC patients in EU and China, respectively, based on results from the Ph 3 IMbrave150 trial
“The results of the IMbrave150 study mark a breakthrough in the treatment of advanced liver cancer, one of the few cancers with a rising death rate and limited options in the first-line setting,” said Dr Arndt Vogel, Professor of Medicine at Hannover Medical School. “After many failures in the last 12 years, the combination of Tecentriq and Avastin shows improvement in overall survival compared to sorafenib and offers patients the opportunity for improved disease control with a high overall response rate.”
European Commission approves Zejula (niraparib) as 1L monotherapy maintenance treatment in advanced ovarian cancer
Clara MacKay, Chief Executive Officer, World Ovarian Cancer Coalition, said: “Having a new first-line maintenance option for patients with platinum-responsive advanced ovarian cancer in Europe — regardless of BRCA mutation status — speaks to the important role of PARP inhibitors in the fight against ovarian cancer. We are especially delighted that today's approval means that more women in Europe who are diagnosed with ovarian cancer will have this new treatment option. We appreciate the commitment and scientific leadership required to develop innovative new therapies that address unmet needs in women’s cancer.”
Click here for more Drug/Diagnostics Approval
Regulatory News
FDA accepts for priority review sBLA for Libtayo (cemiplimab-rwlc) for 1L NSCLC patients with ≥50% PD-L1 expression; PDUFA: February 28, 2021
  • The sBLA is supported by results from a Ph 3 trial of Libtayo monotherapy vs platinum-doublet chemo in 1L locally advanced or mNSCLC whose tumor cells expressed PD-L1, including those whose cancers had confirmed PD-L1 expression of ≥50% using the PD-L1 IHC 22C3 pharmDx kit.
  • Ph 3 results were recently presented ESMO 2020 meeting.
  • EMA is also assessing Libtayo in advanced NSCLC with ≥50% PD-L1 expression and a decision is expected in the second quarter of 2021.
  • Libtayo is approved in the U.S. and EU for adults with mCSCC or locally advanced CSCC who are not candidates for curative surgery or curative radiation.
  • Libtayo is being jointly developed and commercialized by Regeneron and Sanofi.
sBLA for CABOMETYX® (cabozantinib) + OPDIVO® (nivolumab) for the Treatment 1L RCC patients Submitted in Japan based on Ph 3 CheckMate -9ER trial results
“Following our recent announcement that the U.S. FDA accepted and granted Priority Review to our supplemental new drug application for CABOMETYX in combination with OPDIVO for the treatment of advanced renal cell carcinoma, we’re excited that our partner Takeda along with Ono have also advanced this combination regimen toward potential regulatory approval in Japan,” said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. “The results of the CheckMate -9ER trial suggest CABOMETYX in combination with OPDIVO may become an important new treatment option for patients with advanced kidney cancer in need of new therapies.”
FDA Grants Orphan Drug Designation for CPI-613® (devimistat) for Treatment of Soft Tissue Sarcoma
“There is a significant unmet need in treatment for soft tissue sarcoma,” said Sanjeev Luther, President and CEO of Rafael Pharmaceuticals. “When a disease is rare, it often does not receive the attention and focus necessary to develop effective treatments for it. We want to be a voice for those diagnosed with hard-to-treat cancers so that they know that they are not forgotten. We are focusing our attention on developing treatments for these cancers. In fact, Rafael is one of the only companies working on a treatment for clear cell sarcoma.” 
Trial Results
Interim Data from Ph 1/2 Trial of GC4419 + SBRT Showed Improved OS in Locally Advanced Pancreatic Cancer Patients
“We’re encouraged by the favorable overall survival benefit in this difficult-to-treat cancer observed in the interim data in this trial, which is the first trial evaluating the anti-cancer activity of one of Galera’s dismutase mimetics in combination with SBRT,” said Mel Sorensen, M.D., President and CEO of Galera. “Galera’s dismutase mimetics are designed to improve radiation therapy by both increasing therapeutic anti-tumor efficacy at higher doses of radiation and by protecting normal cells, and we look forward to advancing the development of this potential combination therapy and expanding into other cancers to improve outcomes for patients undergoing radiotherapy for the treatment of cancer.”
Positive Top-Line Olutasidenib Data from Planned Interim Analysis Of Registrational Ph 2 AML Trial Announced
“We are pleased to announce these compelling top-line data,” said Patrick Kelly, MD, chief medical officer of Forma Therapeutics. “The safety profile and the duration of the response we’re seeing supports the potential for olutasidenib to become a leading therapy for R/R IDH1m AML patients. While the multi-cohort Phase 2 trial is ongoing, this specific cohort was designed to serve as a pivotal study; these efficacy data support an early stop in enrollment in favor of moving the program forward.”
Click here for more Trial Results
Trial/Program Status
No further enrollment in Ph 2 EMERGE trial of vopratelimab + ipilimumab based on interim analysis
"We are disappointed that an early look at the EMERGE data indicates that we will not meet our pre-specified interim criteria for continued enrollment,” said Beth Trehu, M.D., Chief Medical Officer at Jounce Therapeutics. “Less than 50% of the EMERGE patients had emergence of ICOS hi CD4 T cells after ipilimumab treatment, indicating that CD4 T cell activation by CTLA-4 inhibitors may be impaired in PD-(L)1 inhibitor resistant patients. Patients who have progressed on or after PD-1 inhibitor therapies represent a large and growing unmet need and new therapeutic mechanisms may be needed to more effectively treat these patients. We would like to thank the patients, investigators and study teams for their participation in the EMERGE trial.”
Recruitment in Ph 3 FORTRESS trial of balixafortide in metastatic breast cancer completed
"We are pleased to have completed recruitment in this important study in a timely manner. Balixafortide is currently the only potent blocker of CXCR4, a key molecule involved in tumor growth and metastasis, in Phase 3 clinical development for a solid tumor and as such, it has significant potential to improve the lives of patients," said Dr. Frank Weber, Chief Medical and Development Officer at Polyphor. "We would like to take this opportunity to thank first and foremost the patients, but also the investigators and the local staff as well as our employees for their active participation in this study. This great effort has enabled us to complete the recruitment as planned, despite the difficulties caused by the current pandemic."
Click here for more Trial Status
Collated by : Richa Tewari, PhD
Medness Plus
Results from Phase IIIb trial of FASENRA in asthma patients showed the ability to eliminate the use of maintenance oral corticosteroids 
AstraZeneca’s product Fasenra showed positive results in the elimination of the use of oral corticosteroids (ORC) for asthma.The PONENTE, Phase IIIb open-label trial showed that Fasenra was capable of eliminating the use of OCS in OCS-dependent asthma patients with a broad range of blood eosinophil counts. This is a significant development since one of the common modes of treating exacerbations associated with severe asthma is the chronic or intermittent use of OCS. But is known that such frequent use of OCS may have adverse effects.
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: "Around 13.5 million people worldwide with severe asthma currently rely on oral corticosteroids to control exacerbations and prevent hospitalizations. However, over-reliance on oral corticosteroids can also cause significant health risks for patients, as well as additional strain on health systems. These data further support FASENRA’s clinical profile in eliminating oral corticosteroid use across a broader population of severe asthma patients.”
Merck announces positive results from two Phase 3 studies on their investigational 15-valent Pneumococcal conjugate vaccine 
Merck recently announced data from two of their Phase 3 studies that are underway to determine the safety, efficacy and immunogenicity of the company’s investigational 15-valent pneumococcal conjugate vaccine, V114. These two studies are a part of the V114 Phase 3 clinical development program that consists of 16 trials that is investigating the tolerability and immunogenicity of V114 in different population such as those who have an increased risk of pneumococcal disease. The results from these current two studies will be presented later in future scientific congress. The company plans to file for global regulatory license applications by the end of this year.
“Pneumococcal disease in adults is on the rise globally, in part driven by disease-causing serotypes not targeted by the currently available pneumococcal conjugate vaccine,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “These data provide important information about the potential for V114 followed by PNEUMOVAX 23, a polysaccharide vaccine included in more than 90 percent of age-based adult pneumococcal immunization programs globally, to help protect healthy adults and adults who are at increased risk for pneumococcal disease.”
Click here for more MedNess Plus
Collated by : Esha Sehanobish, PhD
Medness Reviews

MIT researchers designed a wearable to help ALS patients communicate
 Amyotrophic lateral sclerosis (ALS), a rare progressive neurodegenerative disorder in which motor neuron dysfunction leads to the inability to speak. Assistant Professor Dr. Canan Dagdevirenat’s group from MIT media lab has developed a low-cost (under $10) wearable sensor that can detect small facial deformations of the skin. This device could potentially help ALS patients to communicate through facial movements.
Professor Stephen Hawking suffered from this debilitating disease for more than five decades. He used to rely on a hand-held clicker for help choosing his words, which were then synthesized to speech. This system works but it’s bulky and cumbersome. Dr. Canan Dagdevirenat became interested in working on ways to help patients with neuromuscular disorders communicate after meeting Stephen Hawking in 2016.
As most ALS patients also eventually become incapable of regular limb movements, typing is also a challenging way to communicate. This newly developed wearable utilizes four piezoelectric sensors embedded in a thin silicone film. The sensors are comprised of aluminum nitride that can detect mechanical deformation of the skin and convert it into a measurable electric voltage. With this device, patients could communicate a variety of emotions, such as “I love you” or “I’m hungry,” with just small facial movements that are measured and interpreted. The wearable sensor’s thickness is so low, it can be hidden under the matched skin tone makeup in the patient's face and make it almost invisible.
Novel PET scan tracer developed for the earlier detection of tauopathies in Alzheimer’s or frontotemporal lobe dementia
 A Japanese research team made an effort to develop a high contrast imaging-based method to enable earlier detection of neurodegenerative disorders characterized by the aggregation of tau protein in the brain. While most Alzheimer’s disease research has been focused on the amyloid-beta plaque, the presence of tau is thought to be more responsible for the development of symptoms.
Usually, abnormal tau deposits in Alzheimer's patients have been visualized using PET scan combined with the injection of molecular probes labeled with radioactive atoms into the body.  One major complication with 11C-PBB3, an imaging probe designed to visualize tau deposits is it breaks down rapidly after injection and does not enter the brain in large concentrations.
To overcome this problem, researchers have chemically modified PBB3 to turn it into a more metabolically stable compound called PM-PBB3, and also labeled it with fluorine-18. The study shows that 18F-PM-PBB3 uptake in the human brain was approximately twice as high as 11C-PBB3, aiding more sensitive detection of tau deposits. In a preclinical mice experiment, 18F-PM-PBB3 binds to tau deposits in brain sections of tauopathy model mice.
Moreover, the probe detected tau aggregates in 39 living patients with diverse tauopathies such as Alzheimer's disease and various frontotemporal lobe dementia, including Pick's disease, progressive supranuclear palsy, and cortico-basal degeneration. The technique could differentiate the types of dementia patients based on the location of the tau aggregates. The research team has already patented the tracer and licensed it to APRINOIA Therapeutics, which is conducting clinical trials in the US, China, and Japan to test it as a diagnostic tool for Alzheimer’s disease.
Collated by :  Rinki Saha 
Conference Coverage - ENA 2020
Abstracts
  1. Aileron Therapeutics Announces Proof-of-Concept Data from Ongoing ALRN-6924 Ph 1b Trial 
  2. Cyclacel Presents Ph 1 Data Showing Safety, Anti-Tumor Activity and Good Oral Bioavailability of Fadraciclib in Patients With Advanced Solid Tumors
  3. Medicenna Presents Updated Results from Phase 2b Recurrent GBM Trial
  4. Mirati Therapeutics announced preliminary results from the Company's mutant KRAS selective inhibitor programs
  5. Rain Therapeutics Announced a Ph 1 Trial Update for the MDM2 Inhibitor, RAIN-32
  6. Revolution Medicine presents data on Intermittent dosing of RMC-4630 + cobimetinib in Phase 1b/2 trial for advanced solid tumors with activating mutations of RAS signaling
  7. Syros Presents Initial Data from Ph 1 Clinical Trial of Oral CDK7 Inhibitor SY-5609
  8. Turning Point Therapeutics Presents Initial Clinical Data From Ph 1 SHIELD-1 Study of Novel MET/SRC/CSF1R Inhibitor TPX-0022 
Medness Business
Onco-News

MHLW grants marketing authorization to manufacture and supply commercial Kymriah® (tisagenlecleucel) for patients in Japan
“Behind our efforts to reimagine medicine with CAR-T cell therapy lies a commitment to build a manufacturing network that brings treatment closer to patients,” commented Steffen Lang, Global Head of Novartis Technical Operations. “The expertise and infrastructure of FBRI, a world-leading manufacturing organization, allows us to bring CAR-T manufacturing to Asia. With the Japan MHLW commercial manufacturing approval, the recent capacity expansion in the US and our ongoing efforts to optimize and evolve our processes, we are well-positioned to deliver this potentially curative treatment option to more patients around the world.” 
Sanofi and Merck to conduct a Ph 2 clinical trial to evaluate the safety, pharmacokinetics, and preliminary efficacy of THOR-707 + KEYTRUDA® (pembrolizumab) in patients with various cancers
“We believe that THOR-707 has the potential to become a foundation of the next generation of immuno-oncology therapies,” said Peter Adamson, Global Head, Oncology Development and Pediatric Innovation, Sanofi. “This collaboration with MSD will enable us to explore whether THOR-707 can increase and expand the effectiveness of KEYTRUDA and improve the outcomes for patients with cancer.”
Click here for mergers , aquisitions and more business news
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 ,  Shilpa Rawal, PhD ,  Debarati Banik  , Divyaanka Iyer , Arundithi Ananthanarayanan and Abhinav Dey 
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