Novartis Announces the Positive Results of Phase III NATALEE trial Evaluating Kisqali

Novartis announced positive topline results from an interim analysis of NATALEE, a Phase III trial evaluating Kisqali® (ribociclib) plus endocrine therapy (ET) in a broad population of patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC) at risk of recurrence. The Independent Data Monitoring Committee recommended stopping the trial early as the primary endpoint of invasive disease-free survival (iDFS) has been met. Kisqali plus ET reduced the risk of disease recurrence significantly more than standard adjuvant ET alone, with consistent benefit in patients with stage II and stage III EBC regardless of nodal involvement.

“While most patients are diagnosed and treated early with the aim to cure breast cancer, the risk of cancer returning, often as metastatic disease, peaks within three years after diagnosis, but never goes away completely,” said Dennis J. Slamon, MD, Director of Clinical/Translational Research, University of California, Los Angeles Jonsson Comprehensive Cancer Center and Chairman and Executive Director of Translational Research In Oncology (TRIO) and NATALEE trial lead investigator. “There is an urgent need for new, well-tolerated options that keep patients cancer-free while maintaining their quality of life.” The NATALEE trial, where ribociclib was given for three years plus ET, was designed with these unmet needs in mind, and it is extremely encouraging that this study met its primary endpoint.”

“The positive topline results from NATALEE represent a significant milestone in our ambition to extend the benefits of Kisqali to patients in earlier stages of breast cancer, building on the legacy of this effective treatment in HR+/HER2- metastatic breast cancer,” said Shreeram Aradhye, M.D., Novartis’ President, Global Drug Development and Chief Medical Officer. “These findings can potentially change the game for patients at risk of recurrence, including those with no nodal involvement, who currently have few well-tolerated options for preventing recurrence.” Our teams are working on submissions to health authorities worldwide in the hopes of bringing Kisqali to many more breast cancer patients.”

These findings extend Kisqali’s legacy in metastatic breast cancer (MBC), where it has consistently demonstrated an overall survival benefit while preserving or improving quality of life in three Phase III trials. In January 2023, updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for breast cancer recommend ribociclib (Kisqali) as the only Category 1 preferred CDK4/6 inhibitor for first-line treatment of patients with HR+/HER2- MBC when combined with an aromatase inhibitor (AI).

FDA Approves Pharming’s Joenja as the First and Only Treatment Indicated for APDS

Pharming Group N.V. announced that Joenja® (leniolisib) had been approved by the US Food and Drug Administration (FDA) for the treatment of activated phosphoinositide 3-kinase delta (PI3K) syndrome (APDS) in adult and pediatric patients 12 years of age and older. Joenja® is the first and only treatment approved in the United States for APDS, a rare and progressive primary immunodeficiency. The FDA evaluated the Joenja® application for APDS under Priority Review, which is granted to therapies that have the potential to significantly improve the treatment, diagnosis, or prevention of serious conditions. Joenja® is set to launch in the United States in early April, with shipments beginning in mid-April.

“The FDA approval of Joenja® is an exciting moment for the APDS community and offers to transform the treatment pathway for patients and families affected by this rare disease,” said Dr. Eveline Wu, MD, MSCR, Division Chief, Paediatric Rheumatology & Associate Professor of Paediatric Rheumatology and Allergy/Immunology at The University of North Carolina School of Medicine. This approval means that they will have access to an approved treatment for the first time, which has the potential to change the standard of care for the patient population suffering from APDS.”

“The approval of Pharming’s Joenja® is an important step toward making a difference in the lives of individuals living with APDS who experience severe, life-altering, and progressive symptoms,” said Vicki Modell, co-founder of the Jeffrey Modell Foundation, an international, non-profit organization dedicated to helping individuals and family members affected by primary immunodeficiency disorders. The FDA’s approval of a treatment option for one of the over 450 primary immunodeficiencies is also a watershed moment for the primary immunodeficiency community as a whole. The Jeffrey Modell Foundation is dedicated to early diagnosis, genetic sequencing, treatments, and, ultimately, future cures for primary immunodeficiencies.”

APDS is a rare primary immunodeficiency first characterized in 2013 and is currently estimated to affect 1 to 2 people per million. Genetic variants cause it in either one of two identified genes, known as PIK3CD or PIK3R1, which are vital to the normal development and function of immune cells in the body. The FDA reviewed Joenja’s New Drug Application (NDA) under priority review and approved the drug based on the results of a multinational, triple-blind, placebo-controlled, randomized Phase II/III clinical trial that evaluated efficacy and safety in 31 patients diagnosed with APDS aged 12 years and older. Data from a long-term, open-label extension clinical trial in which 38 patients received Joenja® for a median of two years were also included in the application.

The European Medicines Agency’s (EMA) Committee for Human Medicinal Products (CHMP) is currently reviewing the Marketing Authorisation Application (MAA) for leniolisib. Pharming anticipates that the CHMP will issue its opinion on the MAA in the second half of 2023.

Cyclerion Therapeutics Receives FDA Orphan Drug Designation for Zagociguat 

Cyclerion Therapeutics declared that the U.S. Food and Drug Administration had granted orphan drug designation to zagociguat for treating mitochondrial diseases. Zagociguat, a CNS-penetrant sGC stimulator, has been developed as a potential therapy for serious diseases involving the CNS, with symptomatic and disease-modifying effects. In a 29-day open-label study of MELAS patients, treatment with zagociguat showed improvements in several biomarkers relevant to the disease, including mitochondrial function, inflammation, cerebral blood flow, functional brain connectivity, and visually evoked brain activation. These findings, combined with preclinical data from studies on cells from mitochondrial disease patients and zebrafish disease models, suggest that zagociguat holds promise as a treatment for MELAS or other mitochondrial diseases.

FDA’s designation of zagociguat as an orphan drug highlights its potential as a groundbreaking therapy for MELAS, a rare genetic mitochondrial disease. He added that Cyclerion is actively working to accelerate the development of this potential treatment to meet the urgent needs of MELAS patients, who currently lack effective therapies.

Peter Hecht, Ph.D., Chief Executive Officer of Cyclerion

Drugs designed to treat, diagnose, or prevent rare diseases affecting fewer than 200,000 people in the United States are eligible for orphan status under the FDA’s Orphan Drug Designation program. Sponsors of drugs granted orphan designation may qualify for various development incentives, such as tax credits for qualified clinical testing, exemptions from prescription drug user fees, and seven-year marketing exclusivity if the drug is approved by the FDA.

Iovance Biotherapeutics Completes Biologics License Application Submission for Lifileucel in Advanced Melanoma

Iovance Biotherapeutics has announced the completion of its rolling Biologics License Application submission for lifileucel to the U.S. Food and Drug Administration. Lifileucel is a therapy using tumor-infiltrating lymphocytes and is intended for the treatment of patients with advanced melanoma that is either unresectable or metastatic, and has progressed following prior anti-PD-1/L1 therapy and targeted therapy, where applicable. This treatment setting currently lacks any FDA-approved therapies.

Positive clinical data from the C-144-01 trial in patients with advanced post-anti-PD1 melanoma supports the BLA submission for lifileucel. Following a productive pre-BLA meeting with the FDA, Iovance is pursuing accelerated approval for this indication. In addition, Iovance has reached an agreement with the FDA on the design of the registrational Phase 3 TILVANCE-301 trial, which will investigate lifileucel in combination with pembrolizumab for advanced frontline melanoma. The TILVANCE-301 trial is expected to support full approval of lifileucel in post-anti-PD-1 advanced melanoma, as well as the registration of lifileucel and pembrolizumab as frontline therapy for advanced melanoma. Startup activities for TILVANCE-301 are ongoing, and the trial is expected to be well underway at the time of potential accelerated approval for lifileucel in advanced post-anti-PD-1 melanoma.

Upon receipt of the complete rolling BLA submission for lifileucel, the FDA has a 60-day window to assess the BLA’s acceptability for review. With the rolling BLA, Iovance was able to submit portions of the application to the FDA on a continuous basis, thereby allowing the FDA to begin the review process as soon as the documents were received. Expedited programs for severe conditions, such as priority review, allow for a quicker six-month review period from BLA acceptance. Moreover, the FDA had previously granted a regenerative medicine advanced therapy designation for lifileucel in advanced melanoma.

BPGbio Announces Expanded Partnership with debra of America for BPM 31510 for Epidermolysis Bullosa Phase II/III Trial

On March 27, 2023, BPGbio Inc (BPG) announced that the company had reached a partnership agreement with Dystrophic Epidermolysis Bullosa Research Association of America (debra of America) for BPGbio’s BPM 31510 for Epidermolysis Bullosa Phase II/III trial, which is anticipated to launch in the second half of the year. As per the agreement, debra of America will support awareness, understanding, and key information toward patient recruitment and advocacy for the clinical trial.

Preliminary evidence from the Phase 1 clinical trial suggests BPGbio’s BPM 31510 appears to be well tolerated and potentially efficacious in improving wound healing in all subtypes of EB patients. Preclinical data demonstrate that BPGbio’s BPM 31510 influences several key elements of the wound healing process to help in the treatment and management of EB wounds.

“We are pleased to expand our partnership with debra of America to our BPM 31510 for EB Phase II/III trial. This is an important milestone in our efforts to launch the next phase of clinical development for our EB drug candidate later this year.”

Niven R. Narain, Ph.D., President and CEO of BPGbio

“Having seen the encouraging results from BPBbio’s Phase I trial for EB, we are excited to partner with them on the next phase and create meaningful advancements that positively impact the EB community.”

Brett Kopelan, Executive Director of debra of America and father to a 15-year-old with a severe form of the disease.

Since 2017, BPGbio has been working with debra of America, using BPGbio’s expertise and innovative research platforms to provide scientific support and advocate on behalf of patients and families affected by EB. On May 23, 2018, US FDA granted orphan-drug designation to BPM 31510 (ubidecarenone) for the treatment of patients with Epidermolysis Bullosa. 

At the beginning of 2023, BPGbio acquired Berg Health LLC.  BPGbio’s EB therapeutics are a vital component of its acquisition of substantially all assets of BERG, LLC, which includes BERG’s proprietary Interrogative Biology® Platform, a strong pipeline consisting of more than a dozen promising candidates in the areas of oncology, neurology, and rare diseases and a robust portfolio of more than 400 U.S. and international granted and pending patents. Similarly, BPGbio, Inc announced the appointment of four key executives.

As per DelveInsigh’s assessment, the total prevalent population of Epidermolysis Bullosa in seven major markets was 42,600+ in 2021, which is anticipated to grow in the coming years. The total number of diagnosed prevalent cases of Epidermolysis Bullosa in the 7MM was observed to be 40,238 in 2020. Similarly, in the United States, EB affects approximately one in every 20,000 children born in the US. In 2021, there were close to 26,900+ prevalent cases of epidermolysis bullosa.

Epidermolysis Bullosa significantly diminishes the quality of life for those living with it. In the more severe cases, patients may succumb early for many reasons, including a severe form of squamous cell carcinoma. Several major pharma and biotech giants are actively working in the Epidermolysis Bullosa market to provide a better treatment option. In recent years, several major clinical development and commercial agreements have been registered in the therapeutic areas. Similarly, BPGbio’s BPM 31510 holds immense potential to transform the Epidermolysis Bullosa treatment scenario.