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MedNess: bite-size biopharma and medtech news

17th March, 2021
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HIGHLIGHTS
Onco-I-Analyse
Aveo Oncology’s Fotivda approved by the US FDA for R/R advanced kidney cancer
On 10th March, the US FDA granted approval to Fotivda (tivozanib), a next-gen VEGF-TKI, for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC), who have progressed on prior ≥2 systemic therapies.
Background: RCC comprises ~4.1% of all new cancer in the US and with a 5-year survival of 16% for metastatic cancer. The armamentarium comprises TKI and checkpoint inhibitors (CHKPTIs) as the current standards of care for 1L treatment. No standard treatment exists for patients who have failed ≥2 systemic therapies.
Details: The approval was based on Phase 3 randomized TIVO-3 study evaluating tivozanib against sorafenib in patients with mRCC who have failed 2 or 3 prior systemic therapies, including a VEGFR TKI other than sorafenib or tivozanib. The NDA was also supported by 3 additional trials providing safety data from >1,000 patients.
The study met the primary endpoint of median PFS by demonstrating an mPFS of 5.6 vs. 3.9 months for tivozanib and sorafenib, respectively (HR: 0.73; p=0.016). Patients with prior CHKPTI and VEGF TKIs received the greatest benefit.
However, mOS was numerically higher in the sorafenib arm (16.4 vs. 19.2 months for tivozanib and sorafenib, respectively; HR: 0.97). ORR was 18% vs. 8% and mDOR was not reached vs. 5.7 months for tivozanib and sorafenib arms, respectively.
Common (≥5%) grade 3/4 laboratory abnormalities were decreased sodium, increased lipase, and decreased phosphate.
Implications: The launch of Fotivda in the US is planned by 31st March, 2021 with Biologics by McKesson as its speciality pharmacy provider. Although tivozanib’s EMA approval came in 2017, the company was involved in a long struggle with the FDA over the increased risk of deaths.
As per an analyst, the first approval in 3L RCC (including patients on prior CHKPTI) and safety data are likely to be the selling points for tivozanib as it showed no improvements in OS.
Aveo has established a sales team of 65 sales reps for the launch and tivozanib is expected a have a wholesale list price of $24,150 per month and peak sales of $417 million.
Tivozanib’s FDA approval has come close to its patent expiry in 2022, however, Aveo plans to apply for a patent extension until 2027.
Collated by : Shilpa Rawal, PhD
Regulatory News
FDA Oncologic Drugs Advisory Committee to Review Status of Six Indications Granted Accelerated Approval
“We are committed to ensuring the integrity of the accelerated approval program, which is designed to bring safe and effective drugs to patients with unmet medical needs as quickly as possible. The program allows the FDA to approve a drug or biologic product intended to treat a serious or life-threatening condition based on an outcome that can be measured earlier than survival that demonstrates a meaningful advantage over available therapies. However, when confirmatory trials do not confirm clinical benefit, a reevaluation must be performed to determine if the approval should be withdrawn. This public meeting of the advisory committee creates an opportunity for external oncology experts and patients with cancer to share input and perspective with the FDA. After this advisory meeting, our staff will consider the committee’s comments and will make final decisions regarding continuing approval of each indication."
US indication for Tecentriq® (atezolizumab) in prior-platinum treated metastatic urothelial carcinoma to be withdrawn
“The Accelerated Approval Program allows people with difficult-to-treat cancers to receive certain new therapies earlier,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “While the withdrawal of Tecentriq for prior-platinum treated bladder cancer is disappointing, Tecentriq continues to demonstrate benefits across multiple cancer types and therefore remains a meaningful treatment option for many patients.”
Click here for more Regulatory News
Trial Results
Failed trial: Phase III CANOPY-2 trial of canakinumab (ACZ885) as 2nd/3rd line treatment in combination with chemotherapy in NSCLC did not meet primary endpoint of OS improvement
“While results from the CANOPY-2 trial are not what we hoped for in patients with advanced or metastatic non-small cell lung cancer who have been treated with other lines of therapy, these data give us valuable insights into IL-1β inhibition,” said John Tsai, MD, Head of Global Drug Development and Chief Medical Officer at Novartis. “Ongoing Phase III studies in non-small cell lung cancer continue, evaluating canakinumab in earlier treatment settings. We sincerely thank the patients and clinical investigators involved in the CANOPY-2 study for their partnership.”
Trial/Program Status
Further enrollment discontinued in the MCGRAW study of SER-401 or fecal microbiota transplant (FMT) + nivolumab in metastatic melanoma
“While we are disappointed to discontinue enrollment, we are encouraged by the opportunity to apply the learnings from this study towards future development programs at Seres that can directly benefit the oncology community in search of new treatment options,” said Matthew Henn, Ph.D., Chief Scientific Officer at Seres. “We want to thank the patients, their care partners, our collaborators and the medical professionals who participated in this study, despite the COVID-19 pandemic, and helped further advance our understanding of the role microbiome therapeutics play in the treatment of cancer.”
Ph 1 Clinical Trial for HPK1 Inhibitor BGB-15025 Initiated
“We are incredibly proud of BeiGene’s research organization, which now has over 450 people, and its ability to discover not only potentially best-in-class cancer treatments but also investigational agents like BGB-15025, which we believe to be among the first HPK1 inhibitors to enter the clinic and represent a novel immuno-oncology approach targeting T cell activation to fight cancer growth,” commented Lai Wang, Ph.D., Senior Vice President, Head of Global Research, Clinical Operations & Biometrics and APAC Clinical Development at BeiGene. “We believe that the unique nature of BGB-15025 and the HPK1 pathway provides us with a compelling scientific rationale for investigating it as a monotherapy and in combination with our anti-PD-1 antibody, tislelizumab. We are excited to advance its clinical development globally.”
Click here for more Trial Statuses
Collated by : Richa Tewari, PhD
MedNess Reviews
Abbott announces pandemic defense coalition to detect future outbreaks
With several lessons learnt from the current global pandemic, Abbott is already preparing for the next one. The company launched a Pandemic Defense Coalition, the first-of-its-kind global scientific and public health partnership aiming for early detection of and rapid response to future pandemic threats through the connection of global centres of excellence in laboratory testing, genetic sequencing, and public health.
The coalition currently includes academic centres and nonprofit organizations in Chicago, Jamaica, Colombia, Brazil, South Africa, Senegal, India and Thailand. Abbott is also in talks to sign on additional public and private organizations.
As a part of the coalition’s efforts, a public database for publishing sequences of viruses will also be set up, so health officials and laboratories can work together to identify if it’s a novel strain or a virus that has previously been detected.
Surveillance will start with local physicians identifying patients with unknown conditions, and having their samples sequenced and shared throughout the network. If a threat is discovered, Abbott will use the data to help develop diagnostics to aid in containing the outbreak, while also working on tests for COVID-19, HIV, malaria and hepatitis.
Abbott previously launched its Global Viral Surveillance Program over 25 years ago to monitor HIV and hepatitis; that program will be folded into the new pandemic coalition.
UCSD spinout pursues gene editing approach for chronic pain
Scientists at the University of California, San Diego, (UCSD) have turned towards gene editing as potential solution for managing chronic pain. The current standard of care for managing chronic pain are usually opioids, however, the opioid epidemic has intensified the need for non-addictive alternatives.
The UCSD team used two gene-editing tools, CRISPR and zinc fingers, to suppress a gene that encodes for a pain-related ion channel protein called NaV1.7 in neurons. According to their study, the treatments, when injected into the spines of mice, led to durable pain relief in three different models of chronic pain.
The technology based on gene therapy, dubbed LATER, has been spun off into a startup called Navega Therapeutics hoping to advance the therapeutic into human clinical trials in the next few years.
The ion channel protein NaV1.7 found in spinal neurons facilitates the transmission of pain signals from the body to the brain. Previous studies found that a loss-of-function mutation in NaV1.7 blocks the perception of physical pain, whereas its over-expression can lead to extreme pain sensitivity.
NaV1.7 has long been viewed as an attractive target for developing chronic pain therapies, however efforts to develop small-molecule drugs against NaV1.7  have failed, mainly because there are several NaV subtypes.
In their approach, the UCSD team tried gene editing as a way to better target NaV1.7 and paired CRISPR with a so-called “dead” Cas9 enzyme, or dCas9, which doesn’t cut DNA, but rather binds to its gene target and fuses it to a repressor domain called KRAB. The result was temporary gene suppression. The UCSD team also developed another way to suppress NaV1.7 based on zinc finger gene-editing technology. After validating the two approaches in cells, the researchers wrapped the tools in adeno-associated viral vectors and injected them in mice. They found that both approaches worked in mouse models of inflammatory pain, neuropathic pain induced by chemotherapy and pain oversensitivity.
The researchers didn’t find any safety issues with the experimental gene therapies and since these gene therapies don’t make permanent genetic changes, unlike other gene therapies approaches, they are likely to produce transient pain relief for durable pain management
Because the UCSD gene therapies don’t make permanent genetic cuts, they are likely to produce transient pain relief, making this a different approach from currently marketed gene therapies that are designed to permanently correct diseases. But they might still offer durable pain management over a certain period, as the effects in mice lasted at least 15 weeks for the paclitaxel-induced polyneuropathy model and 44 weeks for the inflammatory pain model.
The researchers aim to evaluate the full duration of pain relief, the impact of repeat dosing and the effectiveness of the gene therapies in large animals such as monkeys to optimize gene editing approaches in advance of human clinical trials.
Genes and Therapy
Gene Therapy for Sickle Cell Disease, not a cause for cancer- bluebird bio finds; intends to resume trials
bluebird bio’s Phase 1/2 (HGB-206) and Phase 3 (HGB-210) clinical trials for Sickle Cell Disease LentiGlobin gene therapy was suspended in February 2021 when a patient developed acute myeloid leukemia (AML) after five years of treatment were related to the BB305 lentiviral vector (LVV). The therapy inserts a normal copy of the β-globin gene through a lentiviral vector into the patient’s own hematopoietic stem cells. bluebird bio investigated the case and found that the vector had integrated within a gene called VAMP4 in the AML patient. This gene does not seem to be associated with AML, neither influences any other genes that could possibly be. bluebird bio had earlier identified that this patient had many genetic mutations relevant to AML and chromosomal abnormalities. The company believes BB305 LVV vector is not the reason for AML and has submitted the data to the FDA for clearance to resume trials.
FDA approves Novadip Biosciences’ IND application for regenerative bone product NVD-003
The FDA approved Novadip Biosciences’ Investigational New Drug (IND) application for its autologous cell therapy product NVD‑003 for the treatment of Congenital Pseudarthrosis of the Tibia (CPT). CPT is an orphan disease in children with long-term functional disabilities. The approval will allow Novadip to start human trials in young children, between two and eight years of age, suffering from CPT. NVD‑003 is an autologous cell-based bone healing product made from bone forming cells embedded in their self-secreted extracellular matrix together with added hydroxyapatite particles. It will be available in the form of mouldable putty that can be applied by physicians into bone defect areas, and the cells will eventually start growing and transform the biomaterial into bone.
Click here for more on Genes and Therapy
Medness Business
   BioPharma News
ContraFect bags $86.8 million BARDA award for developing first-in-class cell wall lysing antibiotic to fight MRSA
ContraFect Corporation (ContraFect, New York), made an announcement, on March 11th 2021, about receiving $86.8 million from Biomedical Advanced Research and Development Authority (BARDA) to conduct Phase III studies of its anti-MRSA (methicillin resistant Staph aureus) antibiotic, exebacase.
Exebacase is a recombinant-lysin enzyme derived from lysogenic viruses, that dissolves bacterial cell walls to release viral progeny. The antibiotic is expected to show potent activity in dissolving all bacterial cell walls, including that of MRSA.
The award is phased in 2 instalments. $9.8 million will be given for advancement of Phase III trial, DISRUPT (Direct Lysis of Staph aureus Resistant Pathogen Trial) designed to study possible superior potency of exebacase when compared with other antibodies to MRSA. DISRUPT is a US-based randomized, double-blind, placebo-controlled clinical study with 350 enrolled patients. BARDA may award further performance milestone-based payment of $77 million, which will fund FDA product approval and post-approval activities.
ContraFect is a clinical-stage biotechnological company specializing in direct lytic agents (DLAs) as a new mode of treatment for antibiotic-resistant bacterial infections. Their pipeline also includes CF-370 against Pseudomonas aeruginosa and amurin peptides against broad spectrum gram-negative bacterial infections.
Onco-News
AVEO Oncology and BMS to Evaluate FOTIVDA® (tivozanib) + OPDIVO® (nivolumab) Combination in Pivotal Ph 3 TiNivo-2 Trial in IO Relapsed RCC
“With the recent U.S. FDA approval of FOTIVDA in the relapsed/refractory RCC setting, I look forward to further exploring FOTIVDA’s immunomodulatory effects and differentiated tolerability profile in combination with OPDIVO,” said Toni Choueiri, M.D., Director, Lank Center for Genitourinary Oncology; Director, Kidney Cancer Center; Jerome and Nancy Kohlberg Chair and Professor of Medicine, Harvard Medical School, Dana-Farber Cancer Institute. “This combination was first explored in the Phase 1/2 TiNivo study, where it demonstrated favorable tolerability and prolonged PFS using the combination of FOTIVDA and OPDIVO in both treatment naïve and previously treated patients with advanced RCC. The TiNivo-2 Phase 3 study is expected to further our understanding of the activity and tolerability of this combination following prior immunotherapy.”
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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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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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