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MedNess: bite-size biopharma and medtech news

21st July, 2021

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MedNess This Week
HIGHLIGHTS
Onco-I-Analyse
Keytruda shows significant EFS benefit in Phase 3 study in high-risk TNBC
On 15th July, Merck announced that Keytruda (pembrolizumab) in combination with chemotherapy as neoadjuvant therapy and as adjuvant monotherapy showed statistically significant improvements in event free survival (EFS) in the registrational Phase 3 neoadjuvant/adjuvant KEYNOTE-522 in high-risk triple-negative breast cancer (TNBC) patients.
Background: Early stage TNBC is an area of high unmet need with poorer outcomes and survival. High-risk early stage TNBC is also associated with higher recurrence rates within 5 years. Chemotherapy is the only standard of care for high-risk early stage TNBC patients.
Details: Phase 3 KEYNOTE-522 is evaluating Keytruda as a neoadjuvant therapy in combination with chemotherapy and as monotherapy adjuvant treatment vs. neoadjuvant chemotherapy followed by adjuvant placebo in 1,174 high-risk TNBC patients.
At a median follow-up of 39 months, Keytruda arm demonstrated a 37% risk reduction in EFS events compared to placebo arm (p=0.00031). EFS @ 3-years was 84.5% s. 76.8% while RFS @ 3-years was 87% vs. 80.7%. In May, Merck had announced that the trial met the dual primary endpoint of EFS at the fourth interim analysis, with benefit being independent of PD-L1 expression or pCR achievement. PD-L1+ (CPS ≥1) patients experienced an EFS risk reduction of 33%, while PD-L1neg patients had EFS risk reduction of 52%.
The trial continues follow-up for OS, which currently shows a 28% risk reduction in death (p=0.03214). The other primary endpoint of pathological complete response pCR was achieved (64.8% vs. 51.2%, p=0.00055) during the first interim analysis.
Keytruda’s safety profile was consistent with previous data without any new safety signals.
Implications: Merck has submitted the recent data from the trial to the US FDA and is working closely with the regulatory body for sBLA review.
Earlier in February, FDA’s ODAC had unanimously (10-0) voted to defer the regulatory decision until mature EFS data was available. This was followed by a CRL in March. With a 39-month follow-up, the trial has passed the significance bar for EFS and addressed the issues in the CRL as per the company.
It remains to be seen if the FDA will approve Keytruda in both neoadjuvant and adjuvant settings as the trial does not segregate the benefits achieved in different treatment settings.
Collated by : Shilpa Rawal, PhD
Drug Approvals
U.S. FDA Approves DARZALEX FASPRO® + Pomalidomide + Dexamethasone for Patients with Multiple Myeloma After First or Subsequent Relapse
"Clinical studies including APOLLO have continued to show the ability of daratumumab-based combination treatment regimens to significantly reduce the risk of progression in patients with multiple myeloma," said Meletios A. Dimopoulos, M.D.*, Professor and Chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine, Athens, Greece, and principal investigator. "With this approval, we are now able to combine pomalidomide and dexamethasone with a daratumumab subcutaneous option that can be administered in minutes rather than the hours needed for intravenous administration."
U.S. FDA Grants Regular Approval and Expands Indication for PADCEV® (enfortumab vedotin-ejfv) for Patients with Locally Advanced or Metastatic Urothelial Cancer
“The FDA’s decision to convert accelerated approval to regular approval was based on data from the Phase 3 EV-301 trial, which had a primary endpoint of overall survival for patients treated with PADCEV versus chemotherapy,” said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. “With PADCEV, for the first time, physicians can treat advanced urothelial cancer following treatment with a platinum-containing therapy and immunotherapy using an FDA-approved therapy that has demonstrated an overall survival benefit compared with chemotherapy.”
Regulatory News

FDA approves modification in AVM0703-001 study to allow accelerated dosing in NHL trial
“We are pleased that the FDA agreed with our proposal, which leveraged the safety data amassed from the ongoing study and Expanded Access (Compassionate Use) patient data obtained to date,” remarked Janet R Rea, MSPH, Chief Regulatory Officer. “This accelerates our clinical development program and propels it toward an earlier NDA submission.”

FDA Fast Track Designation granted to Berubicin for the Treatment of Recurrent Glioblastoma Multiforme
  • Orphan Drug Designation also was granted by the FDA for Berubicin for the treatment of patients with recurrent GBM.
  • Patient enrollment is ongoing in the study of Berubicin for the treatment of recurrent glioblastoma multiforme.
  • Berubicin treatment of brain cancer patients appeared to demonstrate positive responses that include one durable complete response in a Ph 1 human clinical trial
 Click here for more Regulatory News
Trial Results
FAILED TRIAL: Ph 3 CheckMate-651 Trial of Opdivo + Yervoy vs EXTREME Regimen didn’t meet primary endpoint of OS improvement in 1L SCCHN patients
“Numerous studies have shown long-term survival improvements with the Opdivo plus Yervoy combinationacross various tumor types, bringing benefit to patients around the world,” said Abderrahim Oukessou, M.D., vice president, thoracic cancers, development lead, Bristol Myers Squibb. “In the CheckMate -651 trial, Opdivo plus Yervoy showed a positive overall survival trend relative to EXTREME in patients with squamous cell carcinoma of the head and neck whose tumors express PD-L1, despite the control arm performing better than expected based on historical data. We are disappointed that these results did not reach statistical significance, and we remain committed to advancing research and supporting patients with this difficult-to-treat cancer.”
Leronlimab + carboplatin Trial for mTNBC Demonstrates Safety with 350 mg, 525 mg and 700 mg Dosages; Officially Advances to Ph 2 from Ph 1b
Scott Kelly, M.D., CytoDyn’s Chief Medical Officer and Chairman of the Board, commented, “In April of this year, we shared our early findings with the medical and scientific communities at the Triple Negative Breast Cancer Drug Development Digital Summit and the continued progress of our drug candidate, leronlimab. We believe these safety findings are a tremendous step forward for CytoDyn’s oncology program for all tumors that have the potential to be treated with leronlimab. Safety, quality of life, and toxicity are often the greatest concerns of oncology patients and these findings give great hope for those in need.”
Trial/Program Status
First Patient treated in Ph 1/2a Clinical Trial of LAVA-051 for Multiple Hematological Malignancies
“The dosing of the first patient with LAVA-051 is an important step towards harnessing the therapeutic potential of the Vγ9Vδ2 subset of gamma-delta T cells in the clinic,” said Benjamin Winograd, M.D., Ph.D., chief medical officer of LAVA. “Our preclinical data demonstrate that LAVA-051 targets CD1d-expressing tumors by activating both Vγ9Vδ2 T cells and type 1 NKT cells, leading to robust antitumor activity. These data make us confident that our dual-targeting approach may lead to important new treatment options for CD1d expressing hematological malignancies like CLL, MM and AML, which are devastating, difficult to treat cancers, for which novel treatments are needed.”
First Patient dosed in Ph 1/2a TiTAN Clinical Trial for GEN-011 Neoantigen-Targeted T cell Therapy
“Dosing the first patient with GEN-011 represents an exciting milestone for Genocea and the field of neoantigen-targeted T cell therapy,” said Thomas Davis, M.D., the company’s Chief Medical Officer. “We believe our GEN-011 therapy employs better targeting – using our ATLAS™ platform to select optimal neoantigen targets that drive anti-tumor immune responses and avoid immunosuppressive Inhibigens™ - and better T cells, derived from easily accessible peripheral blood as opposed to the tumor itself. We are grateful to the patients eager to participate in our trial, to our investigators, and to our colleagues here at Genocea for their great dedication to improve patients’ outcomes. We look forward to reporting top-line results from this study on a subset of patients late in the fourth quarter of 2021 or the first quarter of 2022.”
Click here for more Trial Statuses
Collated by : Richa Tewari, PhD 
Genes and Therapy
Autologous Treg cell therapy for amyotrophic lateral sclerosis receives orphan drug designation 
On 7th July, 2021, Coya Therapeutics announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to ALS001, an autologous, expanded Treg (regulatory T cells) cell therapy in development for the treatment of amyotrophic lateral sclerosis (ALS). ALS is a progressive neurodegenerative disease with no meaningful treatments for the patients.  ALS001 has completed the Phase 2a trial that shows its ability to harness the neuro-protective effects of Treg cell therapy - ultimately slowing and halting the progression of ALS.
Gene therapy delivered in the brain restores dopamine in a rare genetic brain disease
Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare genetic disorder characterized by the deficient synthesis of dopamine and serotonin represented by early infancy complications. In a clinical trial of seven children by doctors at the University of California, San Francisco, the functional AADC gene was delivered with an adenoviral vector directly by injecting it into the midbrain. Within months, all seven children recovered the ability to generate dopamine. Many of them started to sit, walk, and talk with assistance for the very first time
.
Click here for more on Genes and Therapy
MedNess Reviews

UCSF Team Develops Neuroprosthesis For Decoding Speech In a Paralyzed Patient
Brain-computer interface technology has been progressing rapidly over the recent years in an effort to restore speech, movement and other daily activities in people paralyzed by stroke, disease or physical injury by relying solely on their own brain signals.
A “neuroprosthesis” developed by team of researchers from the University of California San Francisco may be perhaps the closest yet to restoring natural communication patterns. The “neuroprosthesis” that, once trained on an individual patient’s brain patterns, can eventually translate their thoughts into speech.
A study of their system found it was able to decode entire sentences at once with a median rate of about 15 words per minute and an average 75% accuracy, with a word error rate of just over 25%.
In order achieve to such accuracy, the researchers spent over a year-and-a-half training the system to recognize the brain signals of a single paralyzed patient, a man who lost his ability to communicate and much of his movement following a stroke in his brain stem more than 15 years ago.
The patient was tasked with repeatedly attempting to say 50 words on a list of basic terms like water and family after a high-density electrode array was implanted over his speech motor cortex. The attempts took place over the course of 48 sessions. The recoridngs of the training sessions were analyzed by Deep learning algorithms to pick up on patterns in the patient’s brain signals for each word.
The resulting neural network was combined with a natural-language model able to predict probable next words in a sentence allowing the system to more quickly and accurately produce entire sentences at a time, differentiating this system from most other systems that only allow nonverbal patients to communicate on a letter-by-letter basis.
The core difference between the two methods stems from the neuroprosthesis’ ability to pick up on brain signals sent to the vocal tract, rather than those sent to the arm or hand to type out a word or control a cursor.
Moving forward, the researchers plan on expanding the study to include other severely paralyzed participants. They’re also hoping to expand the vocabulary list and up the system’s word-per-minute rate.

MedNess Business
Onco-News
AstraZeneca receives final regulatory clearance for the proposed acquisition of Alexion from the UK’s Competition and Markets Authority
Marc Dunoyer, Executive Director and Chief Financial Officer, said: “We are very pleased to have secured this critical final clearance from the UK Competition and Markets Authority for the acquisition of Alexion. We look forward to the imminent closing of the transaction so that we may pursue our shared ambition to bring more innovative medicines to patients worldwide and begin AstraZeneca’s next chapter of growth.”
 Collated by: Richa Tewari, PhD 
Editors' Desk
Richa Tewari, PhD
Oncology News
Shilpa Rawal, PhD
Onco I-Analyse
Arundithi Ananthanarayanan
MedNess Reviews
Divyaanka Iyer
Business Review
Debarati Banik
HealthIT
Darpan Chakraborty
Social Media Manager
Nisha Peter, PhD
Managing Editor
Abhi Dey
Consulting Editor
Rinki Saha
BioPharma News
Managing Editor
Shalini Roy Choudhury
Genes and Therapy
Managing Editor
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Content Editors: Richa Tewari , Esha SehanobishRinki Saha ,  Shilpa Rawal, PhD ,  Debarati Banik  , Divyaanka Iyer , Arundithi Ananthanarayanan and Abhinav Dey 
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