FDA Clears J&J’s 2-in-1 Tablet for Prostate Cancer

Johnson & Johnson’s Janssen Pharmaceutical Companies stated that the US Food and Drug Administration (FDA) had approved AKEEGA (niraparib and abiraterone acetate), the first-and-only dual-action tablet combining a PARP inhibitor including abiraterone acetate administered in conjunction with prednisone for the treatment of adult patients with BRCA-positive mCRPC that is detrimental or thought to be harmful, as discovered by an MRI test that the FDA has approved.

“As a physician, I prioritize identifying patients with a poor prognosis, particularly those whose cancers have a BRCA mutation,” stated Kim Chi, M.D., Medical Oncologist at BC Cancer – Vancouver and primary investigator of the Phase III MAGNITUDE research. “The MAGNITUDE study was designed prospectively to identify the subset of patients most likely to benefit from targeted treatment with AKEEGA and to help us understand how we can potentially achieve better health outcomes for patients.”

Prostate cancer is one of the most frequent cancers in the United States, with an anticipated 288,300 new cases and approximately 35,000 deaths in 2023. BRCA gene mutations affect 10 to 15% of people with mCRPC. Patients with BRCA-positive mCRPC are more likely to have an aggressive disease, with a poor prognosis and a shorter survival time.

“The approval of AKEEGA provides an important treatment option for patients with prostate cancer as they consider their future,” said Shelby Moneer, MS, CHES, Vice President of Patient Programmes and Education at ZERO Prostate Cancer. “All men diagnosed with prostate cancer should consider genetic testing, particularly those from racial and ethnic minority groups, who have poorer cancer outcomes.” This is critical in order to eliminate racial and ethnic disparities in prostate cancer health outcomes.”

The FDA approval is based on positive findings from the multi-center, randomized, double-blind, placebo-controlled Phase III MAGNITUDE trial. A statistically significant 47% risk reduction for radiographic progression-free survival (rPFS) was seen in BRCA-positive individuals treated with the combination AKEEGA plus prednisone (Hazard ratio [HR], 0.53; p=0.001). The second interim analysis (IA2), with a median follow-up of 24.8 months in the BRCA-positive subgroup, revealed a consistent trend favoring AKEEGA plus prednisone, with a median rPFS of 19.5 months compared to 10.9 months for placebo and AAP (HR, 0.55 [95 percent CI, 0.39-0.78]).

FDA Approves TALVEY, a First-in-Class Bispecific Therapy for the Treatment of Patients with Heavily Pretreated Multiple Myeloma

The Janssen Pharmaceutical Companies of Johnson & Johnson announced that the FDA has granted accelerated approval to TALVEY (talquetamab-tgvs), a first-in-class bispecific antibody for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody. This indication has been authorized under rapid approval based on response rate and response durability. Continued clearance for this indication is predicated on the clinical benefit being verified and described in the confirmatory trial(s).

TALVEY is a bispecific T-cell engaging antibody that binds to the CD3 receptor on the surface of T cells as well as the G protein-coupled receptor class C group 5 member D (GPRC5D) expressed on the surface of multiple myeloma cells, non-malignant plasma cells, and healthy tissue such as epithelial cells in the skin and tongue. Following an initial step-up phase, TALVEY is approved as a weekly or biweekly subcutaneous (SC) injection, giving clinicians the option to decide the best multiple myeloma treatment schedule for their patients.

“The clinically meaningful efficacy and safety profile observed with talquetamab in heavily pretreated patients in this clinical trial, which included patients treated with prior BCMA-targeted bispecific or CAR-T cell therapy, was noteworthy,” said Ajai Chari, M.D., Director of the Multiple Myeloma Programme and Professor of Clinical Medicine at the University of California, San Francisco. “Patients at this stage have a poor prognosis.” As a first-in-class medication, talquetamab provides a new choice for individuals suffering from this difficult-to-treat blood malignancy.”

The talquetamab Phase II MonumenTAL-1 study (n=187) exhibited considerable overall response rates (ORR) in patients who had undergone at least four prior lines of therapy and had not been exposed to prior T-cell redirection therapy. 73.6% of patients (95% CI, range, 63.0 to 82.4) attained an ORR at the SC biweekly dose of 0.8 mg/kg. With a median follow-up of approximately 6 (range, 0 to 9.5) months following the first response, 58% of responders had a very good partial response (VGPR) or better, with 33% obtaining a complete response (CR).

Bloomsbury Receives Orphan Drug Designation from the FDA for BGT-OTCD for the Treatment of Ornithine Transcarbamylase Deficiency (OTCD)

On August 9th, 2023, Bloomsbury Genetic Therapies Limited disclosed that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to its therapy, BGT-OTCD, a liver-targeted gene therapy for the treatment of Ornithine Transcarbamylase Deficiency.

Earlier in May, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) granted approval to the clinical trial proposal submitted by University College London (UCL), Bloomsbury’s collaborative partner. This green light initiates the phase 1/2 clinical trial named HORACE (Halting Ornithine Transcarbamylase Deficiency with Recombinant AAV in ChildrEn), focusing on pediatric patients with OTCD. The trial is anticipated to commence enrollment in the United Kingdom in the third quarter of 2023.

Having already received an ODD from the European Medicine Agency and the Rare Pediatric Disease Designation from the FDA for BGT-OTCD, we now look forward to leveraging the benefits that this new designation brings, including the provision of post-approval market exclusivity in the US.

Adrien Lemoine, Co-Founder & Chief Executive Officer of Bloomsbury

BGT-OTCD stands as a liver-targeted gene therapy based on AAV-LK03, with the goal of offering a potential curative avenue for individuals grappling with OTCD. This therapy involves a single intravenous injection. AAV-LK03 was specifically chosen due to its strong affinity for liver cells, coupled with its success in addressing other liver-related conditions, such as hemophilia A. 

BGT-OTCD has been granted Orphan Drug Designation (ODD) for the treatment of OTCD by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) and has received Rare Pediatric Disease Designation from the FDA.

Ornithine Transcarbamylase Deficiency (OTCD) stands as a rare genetic disorder with an X-linked pattern of inheritance, characterized by a partial or complete absence of the OTC enzyme. This enzyme plays a vital role in the urea cycle. In individuals affected by OTCD, there’s an accumulation of excess ammonia (hyperammonemia) in the bloodstream due to the impaired function of OTC. This accumulation leads to hyperammonemic decompensations, which manifest as symptoms like vomiting, compromised voluntary movement, and a gradual onset of fatigue. Without proper intervention, these symptoms can escalate to the point of coma and potentially life-threatening complications.

OTC deficiency demonstrates a higher incidence in males compared to females, and its full manifestation is observed exclusively in males. In males, symptoms generally commence within the initial days of life. On the other hand, late-onset OTC deficiency can manifest during childhood, but there have also been cases of onset occurring between the ages of 40 and 50. Around 20% of females who are carriers of the disorder may experience mild symptoms, and in rare instances, they might be severely affected during childhood. The estimated occurrence of OTC deficiency ranges between 1 in 50,000 to 80,000 individuals. Collectively, the estimated frequency of urea cycle disorders stands at 1 in 35,000 individuals.

The prevailing treatment protocol includes adhering to protein-restricted diets and using medications designed to scavenge ammonia. Nonetheless, these methods can considerably affect the quality of life for patients. Moreover, individuals with Ornithine Transcarbamylase Deficiency continue to be susceptible to lifelong risks of decompensation and neurological impairments, which can lead to intellectual disabilities, delays in development, and movement disorders. While a liver transplant stands as the solitary curative measure, it’s frequently not accessible and brings with it notable risks of morbidity and mortality. Additionally, recipients must commit to lifelong immunosuppression and arginine supplementation. The ongoing therapeutics development and clinical trial activities hold the potential to transform the treatment outlook in the upcoming years. 

Genprex Granted FDA Orphan Drug Designation for REQORSA® Immunogene Therapy for the Treatment of Small Cell Lung Cancer

On 10th of August, 2023, Genprex (NASDAQ: GNPX) had announced that the United States Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to the company’s primary drug candidate, REQORSA® Immunogene Therapy (quratusugene ozeplasmid). This designation pertains to the utilization of REQORSA® in treating Small Cell Lung Cancer (SCLC).

In June 2023, alongside the Orphan Drug Designation (ODD) for treating SCLC, the FDA also conferred Fast Track Designation (FTD) to the therapy, REQORSA Immunogene Therapy. This FTD is specifically for utilizing REQORSA in combination with Genentech, Inc.’s Tecentriq® to treat patients with extensive-stage Small Cell Lung Cancer (ES-SCLC) who have not experienced tumor progression following the initial standard treatment involving Tecentriq and chemotherapy. ES-SCLC denotes a stage where cancer has disseminated from one lung to the other or to other body parts, and it stands as the most prevalent form of SCLC.

Furthermore, Genprex was also granted Fast Track Designation by the FDA for two additional indications of REQORSA Immunogene Therapy. These include REQORSA in conjunction with Tagrisso to address non-Small Cell Lung Cancer (NSCLC) in patients who have encountered disease progression following Tagrisso treatment, as well as REQORSA combined with Keytruda for NSCLC in patients who have seen disease progression after Keytruda treatment.

We are excited to receive Orphan Drug Designation from the FDA for REQORSA for patients with SCLC. This FDA Orphan Drug Designation in combination with our recently received FDA Fast Track designation underscores the great need for better treatment options for patients with SCLC,ES-SCLC and NSCLC.  We look forward to initiating the Acclaim-3 clinical trial expected in the fourth quarter of 2023 in order to bring hope of an effective new therapy to patients suffering with this life-limiting cancer.

Rodney Varner, President, Chairman, and Chief Executive Officer at Genprex

The Acclaim-3 clinical trial represents a Phase 1/2 study that follows an open-label approach, encompassing both dose escalation and evaluation of clinical response. This trial is focused on assessing maintenance therapy through the combined usage of REQORSA and Tecentriq® in patients diagnosed with extensive-stage Small Cell Lung Cancer (ES-SCLC). These individuals are specifically those who haven’t encountered tumor progression subsequent to undergoing the initial standard treatment involving Tecentriq and chemotherapy.

Participants enrolled in the Acclaim-3 clinical trial will be included following their initial treatment, which entails 3–4 cycles of carboplatin, etoposide, and Tecentriq. Importantly, these individuals must have attained a state of complete response, partial response, or stable disease. Subsequently, these participants will undergo maintenance therapy involving a treatment regimen of REQORSA and Tecentriq administered every 21 days, continuing until there is evidence of disease progression.

The central objective of the Phase 2 segment of the trial is to establish the rate of progression-free survival at the 18-week mark, commencing from the initiation of maintenance therapy involving REQORSA and Tecentriq in patients affected by extensive-stage Small Cell Lung Cancer (ES-SCLC). Additionally, patient survival will be monitored over the course of the trial. A futility analysis for Phase 2 will be conducted after the 18-week follow-up period is reached for the 25th enrolled and treated patient.

FDA Issues CRL to NDA for Avasopasem in Radiotherapy-Induced Severe Oral Mucositis in HNC

Galera Therapeutics, Inc. (Nasdaq: GRTX) has made an announcement on August 9, 2023, stating that it has been issued a Complete Response Letter (CRL) by the U.S. Food and Drug Administration (FDA) in relation to the New Drug Application (NDA) submitted for avasopasem manganese (avasopasem). This application pertains to the treatment of radiotherapy-induced severe oral mucositis (SOM) in individuals diagnosed with head and neck cancer who are undergoing standard-of-care treatment.

Avasopasem manganese (avasopasem) is a selective dismutase mimetic in development for the reduction of radiotherapy-induced severe oral mucositis (SOM) in patients with locally advanced head and neck cancer (HNC) and for the reduction of radiotherapy-induced esophagitis in patients with lung cancer. 

Within the confines of the Complete Response Letter (CRL), the FDA conveyed that the conclusions drawn from the Phase 3 ROMAN trial, coupled with the accompanying data from the GT-201 trial, do not carry enough weight to definitively substantiate avasopasem’s efficacy and safety in significantly mitigating severe oral mucositis among individuals diagnosed with head and neck cancer. The FDA indicated that an additional clinical trial’s outcomes will be necessary for the purpose of resubmission. 

This response from the FDA is deeply disappointing for Galera and for patients who suffer from severe oral mucositis. We continue to believe in avasopasem’s potential to bring a meaningful benefit to these patients, who currently have no FDA-approved drugs for this debilitating condition. 

Mel Sorensen, M.D., Galera’s President and CEO

As per the further updates, the firm plans to initiate a Type A meeting with the FDA, aiming to comprehend the underlying reasoning behind the FDA’s verdict and to deliberate on the subsequent actions required to reinforce the NDA resubmission for avasopasem’s approval. Moreover, the company will embark on an exploration of strategic options, such as potential partnerships, to further advance the development of both avasopasem and rucosopasem.

The New Drug Application (NDA) dossier for avasopasem comprised information derived from a collective enrollment of 678 patients who participated in two randomized, double-blind, placebo-controlled studies (Phase 3 ROMAN and Phase 2b GT-201). Avasopasem had been awarded Fast Track and Breakthrough Therapy designations by the FDA for its role in alleviating radiotherapy-induced SOM. Additionally, the NDA underwent acceptance for priority review, a designation accorded to applications seeking approval for treatments that, if successful, would represent substantial advancements in the safety or efficacy of managing, diagnosing, or preventing serious conditions in comparison to existing therapies.

PDS Biotech Announces Submission of Phase 3 Protocol to FDA to Initiate VERSATILE-003 Trial

On August 14, 2023, PDS Biotechnology Corporation (Nasdaq: PDSB) made an announcement regarding the submission of an updated Chemistry, Manufacturing and Controls (CMC) package and a Phase 3 multicenter registrational protocol to the U.S. Food and Drug Administration (FDA). This submission is part of the company’s Investigational New Drug (IND) application process and aims to assess the combination of PDS0101 and KEYTRUDA® (pembrolizumab), an anti-PD-1 therapy developed by Merck. The purpose of this evaluation is to treat individuals with recurrent or metastatic human papillomavirus (HPV) 16-positive head and neck squamous cell carcinoma (HNSCC). The protocol was developed in alignment with FDA guidance on pivotal aspects of the Phase 3 program, aimed at supporting a future submission for a Biologics License Application (BLA).

PDS Biotech’s lead candidate, PDS0101, represents a pioneering investigational immunotherapy tailored for human papillomavirus (HPV)-positive cancers. This innovative therapy triggers a focused and robust T cell response directed at HPV through a targeted approach. PDS0101 is administered via subcutaneous injection either as a standalone treatment or in conjunction with other immunotherapies and cancer interventions.

In a Phase 1 study evaluating PDS0101 as monotherapy, the treatment showcased its capacity to induce multifunctional HPV16-specific CD8 and CD4 T cells, with minimal instances of adverse effects. Preliminary data indicate that PDS0101 fosters immune responses that yield clinical benefits, and when combined with other therapies, it exhibits the potential to effectively manage disease by diminishing tumor size, stalling disease advancement, and potentially extending survival. Moreover, the concurrent use of PDS0101 with other treatments doesn’t appear to amplify the toxicity associated with those additional agents.

Submission of the protocol and supportive CMC documents for this Phase 3 registrational trial is an important milestone for PDS Biotech and our VERSATILE-003 program investigating PDS0101 in combination with KEYTRUDA® as a potential treatment for recurrent or metastatic HPV16-positive HNSCC. Interim data from our ongoing VERSATILE-002 Phase 2 clinical trial have been very encouraging, with impressive interim OS and PFS results. With VERSATILE-003, we have an opportunity to confirm the Phase 2 results from VERSATILE-002 in a controlled, Phase 3 clinical trial comparing the combination of PDS0101 and KEYTRUDA® to KEYTRUDA® monotherapy.

Dr. Lauren V. Wood, PDS Biotech’s Chief Medical Officer

The Phase 3 clinical trial, referred to as VERSATILE-003, is a randomized and controlled study that aims to explore the safety and effectiveness of the combination of PDS0101 with KEYTRUDA® as opposed to KEYTRUDA® monotherapy. This study is specifically targeted at patients who have not previously received immune checkpoint inhibitor (ICI) treatment, and who are diagnosed with recurrent or metastatic HPV16-positive HNSCC. In accordance with the protocol, the primary measure of effectiveness for VERSATILE-003 is overall survival (OS).

The Phase 3 research is set to involve approximately 90-100 clinical sites across the globe. PDS Biotech is planning to commence the VERSATILE-003 Phase 3 trial in the final quarter of 2023.