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MedNess: bite-size biopharma and medtech news

14th April, 2021
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MedNess This Week
HIGHLIGHTS
Onco-I-Analyse
Keytruda demonstrated clinically meaningful benefit in DFS in ccRCC post nephrectomy
On 8th April, Merck announced that Keytruda (pembrolizumab) monotherapy prolonged disease-free survival (DFS) as an adjuvant treatment, post nephrectomy, in patients with renal cell carcinoma (RCC) in the Phase III KEYNOTE-564 trial.
Background: Kidney and renal pelvis carcinomas comprise nearly 4% of all cancer cases in the US. ~85% of all kidney cancers are RCC of which ~70% have a clear cell (cc) histology. Patients with localized and regional RCC have very limited treatment options following radical nephrectomy. Sunitinib has a category 3 recommendation as adjuvant therapy for ccRCC and many clinical trials are unable to show benefit in the DFS.
Details: Keytruda was being evaluated as an adjuvant treatment versus placebo in a Phase III KEYNOTE-564 study which included 950 patients. Trial included patients following partial nephroprotective or radical complete nephrectomy and have either intermediate-high risk, high risk, or M1 no evidence of disease ccRCC.
During an interim analysis by Independent Data Monitoring Committee (IDMC), the committee observed that Keytruda showed statistically significant improvement in the primary endpoint of DFS versus placebo. The trial continues to evaluate a key secondary endpoint of OS.
Detailed results will be presented at an upcoming medical meeting and will be submitted to regulatory bodies for approval.
Implications: Keytruda, in combination with axitinib, is approved as 1L treatment for ccRCC (Cat. 2A). Just last week, its combination with Lenvima received a Cat. 1 recommendation by NCCN for 1L RCC based on Phase III CLEAR study. It is also the first checkpoint inhibitor to show clinically meaningful benefit as adjuvant therapy in RCC, thus will be ahead of its rivals in early stage RCC. Keytruda is also being evaluated as monotherapy and in combination with other therapies across various patient segments in RCC.
Collated by : Shilpa Rawal, PhD
Drug Approvals
FDA approves Trodelvy® for mTNBC after it demonstrating improved PFS & OS
“Women with triple-negative breast cancer have historically had very few effective treatment options and faced a poor prognosis,” said Aditya Bardia, MD, MPH, Director of Breast Cancer Research Program, Mass General Cancer Center and Assistant Professor of Medicine at Harvard Medical School, and global principal investigator of the ASCENT study. “Today’s FDA approval reflects the statistically significant survival benefit seen in the landmark ASCENT study and positions sacituzumab govitecan-hziy as a potential standard of care for pre-treated TNBC.”
Regulatory News
  • FDA evalueated the data package including the promising results from Part C of Immutep’s Phase II TACTI-002 trial evaluating efti  + KEYTRUDA® (pembrolizumab) 2nd line PD-X naive HNSCC, and its plans for a trial in 1 st line HNSCC (TACTI-003).
  • Interim clinical data from TACTI-002 was presented at SITC 2020.
  • ORR reported at SITC was approximately 36% (approximately 44% in evaluable patients) for 28 patients receiving efti + KEYTRUDA.
  • A new Ph 2b trial in 1st line HNSCC, TACTI-003, is planned to evaluate the same combination; study is expected to start in mid-2021.
sBLA submitted to FDA for Tecartus® in Adult R/R ALL Patients
“Tecartus has already begun to transform the outlook for many patients with relapsed or refractory mantle cell lymphoma, and we’re encouraged by the data we’ve seen in adult patients with relapsed or refractory ALL, as survival rates among these patients remain poor with the most commonly used therapeutic agents,” said Frank Neumann, MD, PhD, Kite’s Global Head of Clinical Development. “We are working closely with the FDA to progress our application and to bring the benefits of CAR T to patients with this particularly intractable leukemia.”
Click here for more Regulatory News
Trial Results
Opdivo (nivolumab) plus Chemotherapy and Opdivo plus Yervoy (ipilimumab) Demonstrate Superior Survival Benefit Compared to Chemotherapy in Unresectable Advanced or mESCC
“The results for these Opdivo-based combinations represent a significant advancement for patients with esophageal cancer who are often diagnosed after their disease has spread and would benefit from new therapeutic options,” said Ian M. Waxman, M.D., development lead, gastrointestinal cancers, Bristol Myers Squibb. “This study further demonstrates our commitment to pursue combination strategies that improve outcomes for patients with high unmet need, such as those with gastrointestinal cancers.”
FDA recommendation for early termination of Ph 2 clinical trial of ERC1671 (gliovac or sitoiganap) and application for registration trial for treatment of rGBM
Apostolos Stathopoulos, M.D., Ph.D., President and CEO of ERC Belgium, parent company to ERC-USA, added, “We are thrilled that the FDA now recognizes the potential of ERC1671 to treat this intractable disease and major unmet medical need. We believe ERC1671 provides significant hope to patients with recurrent glioblastoma and we are grateful to the FDA’s encouragement to aggressively enter into a registration trial.”
Click here for more Trial Results
Trial/Program Status
World’s first and second AI-designed drugs to enter Ph 1 testing
Andrew Hopkins, CEO of Exscientia said, “Immuno-oncology medicines are bringing benefit to a range of cancer patients. Our selective A2a receptor antagonist addresses a next-generation IO strategy to empower the human immune system by reversing the effects of high adenosine concentrations. We set ambitious therapeutic objectives for this project, especially high selectivity for the A2a receptor and central nervous system (CNS) sparing properties, in order to reduce the likelihood of systemic side effects. Even with these challenging objectives, we were able to discover our candidate molecule within 8 months of project initiation”.
Initiation of UPLIFT Single-Arm Registration Strategy for UpRi in Platinum-Resistant Ovarian Cancer Announced
“We believe this study design, which is an amendment to the ongoing Phase 1 expansion study, allows for significant operational efficiencies and leverages our current momentum in patient enrollment. The study design also allows us the opportunity to fully evaluate the role of the biomarker with endpoints in both the high NaPi2b and overall populations. We are excited to open this cohort to this heavily pretreated patient population with few options,” said Arvin Yang, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Mersana Therapeutics.
Click here for more Trial Statuses
Conference Coverage - AACR 2021
  1. Advaxis Presents Translational Biomarker Data from Ongoing ADXS-503 Ph 1/2 Lung Cancer Trial
  2. Affimed Announces Initial Data from Ph 1 Study of Cord Blood-derived NK Cells Pre-complexed with Innate Cell Engager AFM13
  3. AstraZeneca accelerates early oncology pipeline across key strategic scientific platforms
  4. Bayer to Present New Clinical Data in Indolent non-Hodgkin's Lymphoma and Additional Research on its Oncology Portfolio
  5. Greenwich LifeSciences Presents Immune Response Ph 2b Poster, Showing Peak Immunity after 6 Months of GP2 Treatment, Resulting in 100% DFS from Recurring Breast Cancer
  6. HOOKIPA announces positive preliminary Ph 1 immunogenicity data for its immunotherapy candidates to treat advanced HPV16+ cancers
  7. Interim late-breaking clinical data validate not-alpha profile of THOR-707 (SAR444245), Sanofi’s novel investigational IL-2
  8. Iovance Biotherapeutics Announces Clinical Data Updates for Lifileucel in Advanced Melanoma
  9. New Clinical Responses for AGEN1181 Presented
  10. Rubius Therapeutics Presents Initial Clinical Results from the Ongoing Ph 1/2 Clinical Trial of RTX-240 in Advanced Solid Tumors
  11. Seagen to Highlight Data from Novel Targeted Therapies
  12. Transgene presents initial Ph 1 data of TG6002, highlighting the potential of the intravenous administration of its oncolytic viruses
  13. Zentalis Pharmaceuticals announced initial efficacy and safety data from the Ph 1 dose-escalation portion of ongoing Ph 1/2 clinical trial of ZN-c3 in patients with advanced solid tumors
Collated by : Richa Tewari, PhD
Genes and Therapy
The new CRISPRoff epigenome editing tool may potentiate therapeutic efforts
Scientists at the Whitehead Institute have developed a modified version of the CRISPR-Cas9 genome editing tool called CRISPRoff, which can be used to alter gene expression epigenetically while leaving the DNA sequence unchanged.  It generates a heritable epigenetic memory. The tool is based on the concept of epigenetic gene silencing through methylation. It uses a protein machinery which guided by the guide RNA can tag methyl groups on to specific regions of the DNA. These methylated strands are then silenced, hence the name CRISPRoff. The silencing may be reversed with demethylating enzymes through CRISPRon. Tau protein that is implicated in Alzheimer’s Disease was examined for CRISPRoff and the protein expression was considerably reduced. Other than controlling gene expression, targeting enhancers, and exploring the principles of epigenetic inheritance, this tool needs to be explored for diseases caused by epigenetic as well as genetic changes.
Antisense oligonucleotide (AON) sepofarsen shows lasting vision improvement for Leber congenital amaurosis
In a clinical trial led by the University of Pennsylvania and funded by ProQR Therapeutics, a patient with genetic childhood blindness gained vision after receiving a single dose of an experimental RNA therapy called sepofarsen. The condition, Leber congenital amaurosis (LCA) affects the retina and is commonly caused by mutation in the CEP290 gene. The short RNA molecule works by increasing normal CEP290 protein levels in the eye’s photoreceptors and improving retinal function under day vision conditions. Post intravitreal sepofarsen injection, it reached its peak efficacy after three months. The patient was monitored for 15 months during which there was a large improvement in vision supporting a biological effect from the treatment.
MedNess Business
Onco-News
Alkermes Announces Clinical Trial Collaboration and Supply Agreement With MSD to Evaluate Nemvaleukin Alfa + KEYTRUDA® combination in Patients With Platinum-Resistant Ovarian Cancer
"We are pleased to collaborate with MSD to evaluate nemvaleukin in combination with KEYTRUDA in patients with platinum-resistant ovarian cancer, a patient population for which there are limited treatment options available and overall survival remains low. Importantly, there are no anti-PD-1 treatments currently approved for this tumor type," said Jessicca Rege, Ph.D., Vice President, Head of Oncology at Alkermes. "Nemvaleukin in combination with KEYTRUDA has demonstrated antitumor activity in heavily pre-treated patients with platinum-resistant ovarian cancer in the ongoing ARTISTRY-1 study, with durable and deepening responses observed. We look forward to initiating this phase 3 study to further evaluate the potential clinical utility of this combination in this tumor type and advancing our interactions with regulatory authorities related to potential registration strategies for the combination in platinum-resistant ovarian cancer."
Click here for more on mergers, acquisition and 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
Managing Editor
Shalini Roy Choudhury
Genes and Therapy
Managing Editor
Nisha Peter, PhD
Managing Editor
Abhi Dey
Consulting Editor
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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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