Instant Report

Date: 22-Sep-2020

EMA Committee Recommends Approval Of Bristol Myers Opdivo Plus Yervoy With Two Cycles Of Chemotherapy To Treat Metastatic NSCLC

Bristol Myers Squibb announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approval of Opdivo (nivolumab) plus Yervoy (ipilimumab) with two cycles of platinum-based chemotherapy for the first-line treatment of metastatic non-small cell lung cancer (NSCLC) in adults whose tumors have no sensitizing EGFR mutation or ALK translocation.

The European Commission (EC), which has the authority to approve medicines for the European Union (EU), will now review the CHMP recommendation.

“This positive CHMP opinion reflects the potential for Opdivo plus Yervoy with two cycles of chemotherapy to offer the chance for a longer life to patients across subgroups of metastatic NSCLC, a devastating cancer where unmet needs still exist,” said Abderrahim Oukessou, M.D., vice president, thoracic cancers development lead, Bristol Myers Squibb. “We look forward to the EC’s decision and hope to soon introduce this innovative, dual immunotherapy approach to patients across the EU who may benefit.”

The CHMP adopted the positive opinion based on results from the phase 3 CheckMate -9LA trial, which met the primary endpoint of superior overall survival (OS). The safety profile of Opdivo plus Yervoy and two cycles of chemotherapy was reflective of the known safety profiles of the immunotherapy and chemotherapy components in first-line NSCLC. The full data from the CheckMate -9LA trial were featured in an oral session at the American Society of Clinical Oncology 2020 (ASCO20) Virtual Scientific Program.

To date, the combination of Opdivo plus Yervoy with two cycles of chemotherapy has been approved in nine countries, including the US, for the first-line treatment of patients with metastatic NSCLC. Approval by the EC would mark the third indication for Opdivo plus Yervoy­-based combinations in the EU, following previous approvals in metastatic melanoma and advanced renal cell carcinoma.

Bristol Myers Squibb thanks the patients and investigators who were involved in the CheckMate -9LA clinical trial.

CheckMate -9LA is an open-label, multi-center, randomized phase 3 trial evaluating Opdivo (360 mg Q3W) plus Yervoy (1 mg/kg Q6W) combined with histology-based chemotherapy (two cycles) compared to chemotherapy alone (up to four cycles followed by optional pemetrexed maintenance therapy if eligible) as a first-line treatment in patients with metastatic non-small cell lung cancer (NSCLC) regardless of PD-L1 expression and histology. Patients in the experimental arm (n=361) were treated with dual immunotherapy for up to two years or until disease progression or unacceptable toxicity. Patients in the control arm (n=358) were treated with up to four cycles of chemotherapy and optional pemetrexed maintenance (if eligible) until disease progression or unacceptable toxicity. The primary endpoint of the trial was overall survival (OS) in the intent-to-treat (ITT) population. Secondary hierarchical endpoints included progression-free survival (PFS) and overall response rate (ORR) as assessed by blinded independent review committee. Exploratory analyses from the study evaluated efficacy measures according to biomarkers.

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology, and includes a broad range of clinical trials across all phases, including phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

Yervoy is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activity. Yervoy binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation, including the activation and proliferation of tumor infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also reduce T-regulatory cell function, which may contribute to a general increase in T-cell responsiveness, including the anti-tumor immune response. On March 25, 2011, the US Food and Drug Administration (FDA) approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is approved for unresectable or metastatic melanoma in more than 50 countries. There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types.

Date: 02-Feb-2021

EMA Committee Recommends Approval Of Expanded Label For Mercks Anti-PD-1 Therapy, Keytruda In Certain Patients With Relapsed/refractory Classical Hodg

Merck, known as MSD outside the United States and Canada, announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending approval of an expanded label for Keytruda, Merck’s anti-PD-1 therapy. The opinion is recommending Keytruda as monotherapy for the treatment of adult and pediatric patients aged 3 years and older with relapsed or refractory classical Hodgkin lymphoma (cHL) who have failed autologous stem cell transplant (ASCT) or following at least two prior therapies when ASCT is not a treatment option.

This recommendation is based on results from the pivotal Phase 3 KEYNOTE-204 trial, in which Keytruda monotherapy demonstrated a significant improvement in progression-free survival (PFS) compared with brentuximab vedotin (BV), a commonly used treatment. Keytruda reduced the risk of disease progression or death by 35% (HR=0.65 [95% CI, 0.48-0.88]; p=0.00271) and showed a median PFS of 13.2 months versus 8.3 months for patients treated with BV. The recommendation is also based on supportive data from an updated analysis of the KEYNOTE-087 trial, which supported the European Commission’s (EC) approval of Keytruda for the treatment of adult patients with relapsed or refractory cHL who have failed ASCT and BV or who are transplant ineligible and have failed BV. The CHMP’s recommendation will now be reviewed by the EC for marketing authorization in the European Union (EU), and a final decision is expected in the first quarter of 2021. If approved, this will be the first pediatric indication for Keytruda in the EU.

“This positive opinion reinforces the importance of Keytruda for certain adult and pediatric patients with relapsed or refractory classical Hodgkin lymphoma in the European Union,” said Dr. Vicki Goodman, vice president, clinical research, Merck Research Laboratories. “We look forward to the decision by the European Commission and will continue to expand our clinical development program in blood cancers with Keytruda and our recently acquired investigational therapies to help address the unmet needs of patients.”

Merck is studying Keytruda across hematologic malignancies through a broad clinical programme, including multiple registrational trials in cHL and primary mediastinal large B-cell lymphoma and more than 60 investigator-initiated studies across 15 tumors. In addition to Keytruda, Merck is evaluating two clinical-stage assets for the treatment of patients with hematologic malignancies: MK-1026 (formerly ARQ 531), a Bruton’s tyrosine kinase inhibitor, and VLS-101, an antibody-drug conjugate targeting ROR1.

KEYNOTE-204 (, NCT02684292) is a randomized, open-label, Phase 3 trial evaluating Keytruda monotherapy compared with BV for the treatment of patients with relapsed or refractory cHL. The primary endpoints are PFS and overall survival (OS), and the secondary endpoints include objective response rate (ORR), complete remission rate (CRR) and safety. The study enrolled 304 patients, aged 18 years and older, who were randomized to receive either:

Keytruda (200 mg intravenously on Day 1 of each three-week cycle for up to 35 cycles), or; Brentuximab vedotin (1.8 mg/kg [maximum 180 mg per dose] intravenously on Day 1 of each three-week cycle for up to 35 cycles).

Hodgkin lymphoma is a type of lymphoma that develops in the white blood cells called lymphocytes, which are part of the immune system. Hodgkin lymphoma can start almost anywhere – most often in lymph nodes in the upper part of the body, with the most common sites being in the chest, neck or under the arms. Worldwide, there were approximately 83,000 new cases of Hodgkin lymphoma diagnosed, and more than 23,000 people died from the disease in 2020. In the EU, there were nearly 20,000 new cases of Hodgkin lymphoma diagnosed, and nearly 4,000 people died from the disease in 2020. Classical Hodgkin lymphoma accounts for more than nine in 10 cases of Hodgkin lymphoma in developed countries.

Keytruda is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,300 trials studying Keytruda across a wide variety of cancers and treatment settings. The Keytruda clinical program seeks to understand the role of Keytruda across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with Keytruda, including exploring several different biomarkers

Date: 05-Apr-2021

EMA Committee Recommends Approval Of Secura Bios Copiktra To Treat Relapsed Or Refractory CLL And FL

Eloxx Pharmaceuticals announced it has acquired Zikani Therapeutics, in an all-stock transaction, with the potential to create a leader in ribosomal RNA-targeted therapies for treatment of rare diseases and oncology. Sumit Aggarwal, previously the president and chief executive officer of Zikani, has been named president and chief executive officer of Eloxx, and Vijay Modur, M.D., Ph.D., who was Zikani’s chief scientific and medical officer, has been named Eloxx’s head of research and development.

“With the strength of our ELX-02 program for cystic fibrosis, this acquisition provides us with the opportunity to amplify the potential of our innovative science by developing a new class of therapies to treat diseases with limited to no treatment options under the stewardship of leaders with a proven ability to translate technology into treatments for patients,” said Tomer Kariv, Eloxx chairman.

“We are excited about the potential of ELX-02 and combining the companies opens the door to build a leadership position in genetic therapy by rapidly developing treatments that can restore functional proteins in patients with nonsense mutations in their RNA,” said Aggarwal. “The combined capabilities of Eloxx and Zikani in chemistry, biology, regulatory and drug development, including Zikani’s TURBO-ZMTM synthetic chemistry platform for designing macrolide-based Ribosome Modulating Agents (RMAs), along with a committed leadership team and talented employees, will further accelerate our ability to impact the lives of those who have rare diseases with the type of urgency and novel thinking that they deserve,” added Aggarwal.

ELX-02 is currently in phase 2 clinical trials in Cystic Fibrosis (CF) patients affected by nonsense mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The investigational therapy has shown strong activity across a full range of mutations in CF preclinical models. In phase 1 testing, ELX-02 was generally well- tolerated and demonstrated high bioavailability with consistent pharamacokinetics across both single and multiple-dose studies.

“The phase 2 trials are designed to validate the safety of ELX-02 and assess its biological activity. We look forward to completing enrollment in the first four treatment arms by mid-year and reporting data from these treatment arms in the second half of this year,” said Dr. Modur.

In addition to CF, the company plans to file an IND in 2022 for what could potentially become the first oral therapy for protein restoration for patients with nonsense mutations in Recessive Dystrophic Epidermolysis Bullosa (RDEB) and Junctional Epidermolysis Bullosa (JEB). RDEB is an incurable, extremely painful and often fatal skin blistering condition caused by a lack of collagen type VII that is estimated to affect more than 3,000 people worldwide. JEB is the most severe form of EB, with most patients dying in infancy.

By extending the application of ribosomal RNA modulation to the readthrough of nonsense mutations in tumor suppressor genes, the company is also rapidly advancing preclinical research for familial adenomatous polyposis (FAP), an inherited pre-cancerous colorectal disease frequently caused by nonsense mutations in the adenomatous polyposis coli (APC) gene.

Nonsense mutations cause approximately 10-12 per cent of rare inherited diseases. ELX-02 along with the TURBO-ZM library of compounds is anticipated to significantly expand to include the treatment of many other rare diseases and certain cancers.

“We’re pleased to welcome Sumit and Vijay to the Eloxx leadership team. They demonstrated their ability to transform Zikani by following the science and pursuing the creation of a new class of therapies on behalf of patients with unmet medical need. We want to extend our thanks and appreciation to Dr. Greg Williams for his stewardship of Eloxx and his commitment to advancing the critical work of the company. We are pleased that Greg will continue to advise Eloxx to facilitate a smooth transition,” said Kariv.