FDA Expands GSK’s Jemperli Approval for Endometrial Cancer

GSK plc announced that the US Food and Drug Administration (FDA) has approved Jemperli (dostarlimab) in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent for the treatment of adult patients with mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) endometrial cancer. Priority Review was granted to the supplemental Biologics Licence Application (sBLA) supporting this new indication, and it was authorized ahead of the Prescription Drug User Fee Act action deadline.

“Today’s expanded approval of Jemperli redefines the treatment landscape for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer,” stated Hesham Abdullah, Senior Vice President, Global Head of Oncology Development at GSK. Chemotherapy alone has previously been the standard of care, with many patients seeing cancer progression. In the RUBY trial, Jemperli plus chemotherapy reduced the risk of disease progression or death by 71% compared to chemotherapy, indicating a statistically significant and clinically relevant effect. These findings, as well as today’s approval, reinforce our optimism in Jemperli’s ability to change cancer treatment as a backbone immuno-oncology therapy.”

Jemperli is now approved for use in combination with chemotherapy for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer. Jemperli is already licensed in the United States as a monotherapy in adult patients with dMMR recurrent or advanced endometrial cancer who have progressed on or after a prior platinum-containing regimen and are not candidates for curative surgery or radiation.

Interim analysis data from Part 1 of the RUBY/ENGOT-EN6/GOG3031/NSGO phase III trial, which show a solid median duration of follow-up of 25 months, support the FDA clearance. The trial fulfilled the primary goal of investigator-assessed progression-free survival (PFS) in the dMMR/MSI-H population, revealing a statistically significant and clinically relevant advantage in patients treated with Jemperli plus carboplatin and paclitaxel. The probability of disease progression or death was reduced by 71% in the dMMR/MSI-H population. Part 1 of the RUBY trial is still assessing overall survival (OS) in the ITT population, which is a dual-primary endpoint alongside investigator-assessed PFS. 

The sBLA supporting this new indication was examined through the FDA Oncology Centre of Excellence Project Orbis Framework, which allowed for simultaneous submission and review by the US and other international regulatory authorities. The application is still being reviewed as part of Project Orbis in Australia, Canada, Switzerland, Singapore, and the United Kingdom. The European Medicines Agency is also reviewing a marketing authorization application.  

Biogen to Acquire Reata Pharmaceuticals

Biogen Inc. and Reata Pharmaceuticals, Inc. signed a definitive agreement under which Biogen would acquire Reata for $172.50 per share in cash, representing an enterprise value of approximately $7.3 billion. Reata has made tremendous progress in creating medicines for critical brain diseases that affect cellular metabolism and inflammation. The FDA-approved SKYCLARYS® (omaveloxolone) by Reata is the first and only licensed treatment for Friedreich’s ataxia (FA) in the United States, with a commercial launch planned and a European regulatory assessment underway. Furthermore, Reata is developing a portfolio of novel products for a variety of neurological diseases.

“With extensive expertise in rare disease product development and global commercialization, as demonstrated by SPINRAZA and the recent launch of QALSODY, we believe Biogen has the foundation in place to accelerate the delivery of SKYCLARYS to patients around the world,” said Biogen President and Chief Executive Officer Christopher Viehbacher. “This is a once-in-a-lifetime opportunity for Biogen to accelerate our near-term growth trajectory, and SKYCLARYS is an excellent complement to our global portfolio of neuromuscular and rare disease treatments.”

“Biogen’s expertise and commercial footprint make it the optimal choice to help SKYCLARYS realise its full potential,” stated Warren Huff, Chairman and CEO of Reata. “With its clear understanding of the rare disease patient journey and existing commercial infrastructure, we believe Biogen will establish SKYCLARYS as the gold standard of care in the treatment of this devastating genetic disease.”

Enhertu Shows Survival Boost in HER2+ Solid Tumors

The initial findings from the ongoing DESTINY-PanTumor02 Phase II trial have shown that Enhertu (trastuzumab deruxtecan), a specifically engineered HER2-directed antibody-drug conjugate (ADC), provided clinically meaningful improvements in both progression-free survival (PFS) and overall survival (OS) for patients with previously treated advanced solid tumors expressing HER2. These positive outcomes were observed in two secondary endpoints of the trial.

During the primary analysis, Enhertu exhibited enduring responses based on the confirmed objective response rate (ORR), which is the main goal of the trial, as well as the duration of response (DoR). These results reinforce the findings from an earlier interim analysis presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

AstraZeneca and Daiichi Sankyo are jointly developing and commercializing Enhertu. Dr. Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer at AstraZeneca, emphasized the significance of these results, stating that Enhertu shows promise as an important treatment option for patients with HER2-expressing cancers who currently lack targeted therapies. He also expressed the commitment to work with health authorities to expedite the availability of Enhertu for these patients.

Mark Rutstein, Global Head of Oncology Development at Daiichi Sankyo, highlighted the importance of these updated results in reshaping the treatment landscape for advanced HER2-expressing cancers, where patients have limited treatment choices and face a challenging prognosis. The demonstrated overall survival benefits of Enhertu in these patients represent a notable advancement in potential care standards and offer new hope for those with HER2-expressing cancers.

The DESTINY-PanTumor02 Phase II trial assesses the efficacy and safety of Enhertu in patients with previously treated locally advanced, unresectable, or metastatic HER2-expressing solid tumors, including biliary tract cancer, bladder cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and other cancers.

The safety profile of Enhertu observed in the primary analysis was consistent with previous data and other trials, with no new safety concerns identified. The rates and severity of interstitial lung disease (ILD) were similar to those seen in previous Enhertu trials, and there were few Grade 5 ILD events, as assessed by an independent adjudication committee.

The gathered data will be presented at an upcoming medical conference and will contribute to ongoing discussions with health authorities worldwide.

FDA Rejects Citius’ Revived IL-2 Therapy for Lymphoma

The FDA has turned down Citius Pharmaceuticals’ marketing application for Lymphir, an updated version of a lymphoma therapy that was withdrawn from the market a few years ago. The rejection, communicated through a complete response letter (CRL), was not related to any concerns regarding the drug’s clinical effectiveness or safety, nor its proposed prescribing information, according to Citius, which is based in New Jersey.

The reason for the FDA’s decision was the requirement to include “enhanced product testing” in the application, which had been previously agreed upon with the FDA. Leonard Mazur, Citius’ CEO, stated that the company intends to provide the necessary data and is actively working with the FDA to obtain approval.

Lymphir is a recombinant fusion protein designed to combine an IL-2 binding domain with diphtheria toxin fragments, aiming to target and eliminate leukemic cells. Citius is seeking approval in the US for the treatment of patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL), a form of non-Hodgkin lymphoma, after they have received at least one prior systemic therapy.

Lymphir is a reformulated and purified version of Eisai’s Ontak, which was initially approved by the FDA in 1999 and received approval for the CTCL indication in 2008. However, it was later withdrawn from the market in 2014 due to manufacturing issues, including problems with the purity of the recombinant protein in the drug.

In 2016, Eisai licensed the rights to Lymphir, including the reformulation, to the US subsidiary of Indian drugmaker Dr. Reddy’s Laboratories. Subsequently, Dr. Reddy’s sold the rights to Citius in 2021, except for certain Asian markets, such as Japan, which were still held by Eisai, in exchange for an upfront payment of $40 million and $70 million in development and regulatory milestones.

A phase 3 trial demonstrating results consistent with the earlier formulation was completed at the end of 2021, showing an objective response rate of 36%. A biologics license application in CTCL was filed in the third quarter of 2022.

Eisai obtained Japanese approval for the new version under the brand name Remitoro in March 2021, for both CTCL and peripheral T-cell lymphoma (PTCL), based on a mid-stage study conducted in Japanese patients that demonstrated a response rate of approximately 32% in CTCL and 41% in PTCL.

Lymphir was granted orphan drug designations from the FDA for PTCL in 2011 and CTCL in 2013. It is also being investigated in studies involving solid tumors in combination with Merck & Co’s cancer immunotherapy Keytruda (pembrolizumab), as well as a pre-treatment before lymphodepletion and CAR-T therapy for patients with B-cell lymphomas.

Citius believes that the CTCL market represents an opportunity of approximately $300 to $400 million, with even greater potential in PTCL and immuno-oncology indications.

In addition to Lymphir, the biotech company is also working on developing antibiotic therapy Mino-Lok for catheter- and central line-related bloodstream infections (CRBSI/CLABSI), with a phase 3 readout expected soon, as well as a topical formulation of halobetasol and lidocaine in phase 2b, aiming to become the first FDA-approved therapy for hemorrhoids.

FDA Grants Fast Track Designation to IVS-3001 for the Treatment of Renal Cell Carcinoma

On July 31, 2023, Invectys announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to its revolutionary product, IVS-3001. With the achievement of this important milestone, cancer therapy choices will advance, and patient outcomes will be improved.

“We are thrilled to receive the FDA’s Fast Track designation for IVS-3001,” said Dr. Jake Kushner, CEO of Invectys. “This recognition further validates the potential of our CAR-T cell therapy in revolutionizing cancer treatment for patients with solid tumors. The dedicated team at Invectys, as well as our partners, are committed to bringing this innovative therapy to the clinic and making a meaningful difference in the lives of cancer patients.”

IVS-3001 is a cutting-edge CAR-T cell immunotherapy that targets HLA-G, a tumor-specific antigen, and a rarely used immunological checkpoint. This molecule shields the fetus from the mother’s immune system and is usually only expressed during pregnancy. HLA-G, however, can be used by tumors to develop a sterile microenvironment, avoiding the immune system, and fostering tumor growth in cancer. IVS-3001 intends to reactivate the body’s natural defense to successfully fight cancer by focusing on this mechanism.

IVS-3001 was granted the Fast Track designation as a result of the strong data from the Investigational New Drug Application (IND) submission and its potential to fill a medical need for patients with locally advanced or metastatic clear cell Renal Cell Carcinoma who have failed or become intolerant to conventional Renal Cell Carcinoma therapies and have the HLA-G gene.

Renal Cell Carcinomas are thought to be the 8th most common adult malignancy, representing 2% of all cancers, and account for 80-90% of primary malignant adult renal neoplasms. The treatment landscape of Renal Cell Carcinoma is governed by targeted therapies, and immunotherapies. Most of the targeted drugs used to treat kidney cancer work by blocking angiogenesis (growth of the new blood vessels that feed cancers) or important proteins in cancer cells (called tyrosine kinases) that help them grow and survive. Some targeted drugs affect both. The anticipated approval and launch of emerging therapies such as IVS-3001, among others, are expected to transform the Renal Cell Carcinoma treatment scenario in the upcoming years. 

Biohaven’s Taldefgrobep Alfa Receives EU Orphan Drug Designation for Spinal Muscular Atrophy (SMA)

On July 31, 2023, Biohaven Ltd. (NYSE: BHVN) announced that it received orphan medicinal product designation from the European Commission (EC) for taldefgrobep alfa, a novel anti-myostatin adnectin, for the treatment of Spinal Muscular Atrophy (SMA)

Taldefgrobep alfa (also known as BHV2000) is a modified adnectin designed to specifically bind to myostatin (GDF-8). Taldefgrobep is a fully human anti-myostatin recombinant protein that lowers free myostatin and acts as an Activin 2b receptor antagonist with the myostatin-taldefgrobep complex. Adnectins are an established proprietary protein therapeutic class based on human fibronectin, an extracellular protein that is naturally abundant in human serum. 

To evaluate the efficacy and safety of Taldefgrobep Alfa in participants with Spinal Muscular Atrophy (RESILIENT) (NCT05337553), Biohaven is currently enrolling in a Phase 3 clinical trial of taldefgrobep in SMA. Taldefgrobep has the potential to be a unique therapeutic for improving muscular function in Spinal Muscular Atrophy by blocking myostatin. Taldefgrobep has a distinct, dual mechanism of action that sets it apart from other myostatin inhibitors. It works as a receptor antagonist and binds to myostatin to lower overall myostatin levels while also preventing myostatin signaling in skeletal muscles.

Irfan Qureshi, MD, Chief Medical Officer, Biohaven commented, “We are delighted that the European Commission granted orphan drug designation for taldefgrobep alfa for the treatment of SMA. Children and adults living with Spinal Muscular Atrophy experience significant muscle weakness and functional impairments affecting their quality of daily life, and a substantial unmet medical need persists. We are excited about the potential for taldefgrobep alfa to improve the lives of patients and families affected by SMA.”

Spinal Muscular Atrophy (SMA) is a rare genetic neuromuscular disorder. It leads to progressive muscle weakness and atrophy (wasting away) due to the degeneration of motor neurons responsible for transmitting signals from the brain to the muscles, resulting in limited mobility and muscle control. As per the estimate, the prevalence of all types of Spinal Muscular Atrophy has been estimated to be 4-7.8 per 100,000 live births. Approximately 80% of Spinal Muscular Atrophy patients have the Werdnig-Hoffmann form, i.e. Type 1 SMA. It is observed that 1 in 50 people (approximately 6 million Americans) are carriers. With the approval of three therapies for Spinal Muscular Atrophy (Spinraza, Evrysdi, and Zolgensma (gene therapy)), some of the unmet needs for the treatment of Spinal Muscular Atrophy were fulfilled. Moreover, the management of Spinal Muscular Atrophy is also based on supportive and multidisciplinary care with a focus on reducing complications and improving quality of life. Several clinical activities are going to address Spinal Muscular Atrophy.