FDA Grants Orphan Drug Designation to Osemitamab for Pancreatic Cancer
Transcenta Holding Limited has announced that the U.S. Food and Drug Administration (FDA) has awarded Orphan Drug Designation to Osemitamab (TST001), a highly potent humanized monoclonal antibody that enhances ADCC (antibody-dependent cell-mediated cytotoxicity), for treating pancreatic cancer patients. This marks the second time Osemitamab (TST001) has received Orphan Drug Designation, with its first designation being in 2021 for treating gastric cancer and gastroesophageal junction cancer.
Orphan drugs are intended for the prevention, treatment, and diagnosis of uncommon diseases. The US FDA’s Orphan Drug Designation (ODD) pertains to drugs and biologics aimed at rare diseases that affect fewer than 200,000 patients in the United States annually. Once certified, these drugs may benefit from tax incentives, a seven-year period of market exclusivity after approval, and other policy-based benefits in the United States.
Treating pancreatic cancer poses a significant challenge since it is frequently detected at an advanced stage, with few effective treatment options available. The disease’s prognosis is typically poor, with a 5-year survival rate of approximately 10% at diagnosis and a median overall survival rate that barely surpasses nine months for advanced or metastatic cases. As per the National Institutes of Health, an estimated 62,000 people will be diagnosed with pancreatic cancer in 2022, and nearly 50,000 will succumb to the disease.
At the 2022 International Gastric Cancer Congress, Transcenta previously shared preliminary data on the anti-tumor activity of Osemitamab (TST001) in pancreatic cancer. The data revealed that administering Osemitamab (TST001) as a monotherapy resulted in a sustained partial response in a patient with pancreatic cancer who had low expression of Claudin18.2 and had already undergone several cycles of chemotherapy. Preclinical research has demonstrated that Osemitamab (TST001) exhibits potent anti-tumor effects in pancreatic cancer tumor models expressing Claudin18.2, regardless of Kras mutation status.
FDA Clears Keytruda/Padcev Regimen for Bladder and Urothelial Cancer
Merck has announced that the U.S. Food and Drug Administration (FDA) has given its approval for the use of KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with Padcev, for the treatment of adult patients suffering from locally advanced or metastatic urothelial carcinoma who cannot receive cisplatin-containing chemotherapy. The approval of this indication has been granted under accelerated approval based on the tumor response rate and the durability of the response. The continued approval of this indication may be subject to confirmation of clinical benefits in the subsequent trials. This marks the first time that an anti-PD-1 therapy has been approved in the United States in conjunction with an antibody-drug conjugate for these patients.
The approval of KEYTRUDA in combination with Padcev is based on data from the KEYNOTE-869 trial, which involved Cohort A and Cohort K of the dose escalation cohort and was conducted with the collaboration of Seagen and Astellas. The median follow-up time for the dose escalation cohort + Cohort A was 44.7 months, and for Cohort K, it was 14.8 months. In a combined efficacy analysis of the dose escalation cohort, Cohort A and Cohort K, the KEYTRUDA and Padcev combination therapy showed an objective response rate of 68%, with complete and partial response rates of 12% and 55%, respectively. The median duration of response for the dose escalation cohort + Cohort A was 22.1 months, and for Cohort K, it was not reached.
KEYTRUDA treatment can result in immune-mediated adverse reactions that could be life-threatening or severe and can impact multiple organs or body systems simultaneously. These reactions, including but not limited to pneumonitis, dermatologic reactions, colitis, hepatitis, endocrinopathies, nephritis, solid organ transplant rejection, and complications related to allogeneic hematopoietic stem cell transplantation, may manifest at any time during or after KEYTRUDA therapy. Please note that the listed immune-mediated adverse reactions are not exhaustive and may not encompass all possible severe or fatal immune-mediated adverse reactions.
Prompt identification and proper management of immune-mediated adverse reactions are crucial to ensure the safe administration of KEYTRUDA. Depending on the severity of the adverse reaction, treatment with KEYTRUDA may need to be suspended temporarily or permanently, and corticosteroids may need to be administered if deemed necessary. Infusion-related reactions may also occur and can be severe or life-threatening. As KEYTRUDA can cause harm to a developing fetus, caution must be exercised when administering the drug to pregnant women due to its mechanism of action.
The Journal of Clinical Oncology previously published findings from the dose escalation and Cohort A. In February 2020, the combination therapy received Breakthrough Therapy designation from the FDA. Today’s approval under the Accelerated Approval Program is based on a surrogate endpoint and aims to fulfill an unmet medical need for a severe condition. The ongoing Phase 3 EV-302/KEYNOTE-A39 trial will serve as the U.S. confirmatory trial for the accelerated approval, as well as the foundation for global registration. The trial is assessing the clinical benefit of KEYTRUDA in combination with enfortumab vedotin in patients with previously untreated advanced urothelial cancer.
Ipsen’s Cabometyx Gets Rejection by NICE for Thyroid Cancer
According to revised NICE guidance, the NHS should not use Ipsen’s Cabometyx for patients with differentiated thyroid cancer who have either not responded to or are ineligible for radioactive iodine therapy. Since the drug’s approval in this setting last year, the UK’s medication cost-effectiveness watchdog has been assessing the usage of Cabometyx (cabozantinib) in these patients, whose alternatives are currently confined to supportive care.
NICE acknowledged in its appraisal statement that Cabometyx extends the time people have before their cancer worsens. However, due to the manner, Ipsen conducted the major study that supported approval, it stated that there is no clear evidence that the medicine helps patients live longer lives. The medicine improved median progression-free survival (PFS) to 11 months in that research, which compared Cabometyx to placebo alongside supportive treatment, from just under 2 months in the comparator arm.
There was no statistically significant change in overall survival, and the NICE review committee stated that patients were not followed up on long enough and that the trial contained “a lot of incomplete information.” It also mentions that just a subgroup of the individuals in the research received Cabometyx second-line, which reduced the sample size and made the demonstrated benefits questionable. According to Ipsen, there are approximately 3,900 new cases of thyroid cancer diagnosed in the UK each year, with differentiated thyroid cancer accounting for 90% to 95% of cases.
Although radioactive iodine therapy has a high cure rate, a small percentage of patients may not respond to it or cannot tolerate it and must be treated with chemotherapy. If their disease worsens despite this, they will have no therapeutic choices unless they have particular cancer-associated mutations that allow them to be treated with targeted medications like lenvatinib or sorafenib. NICE already approves Cabometyx for various indications, including first-line kidney cancer therapy and treatment of previously treated liver cancer. The draught document on thyroid cancer is now up for public comment, with a final decision due in July.
Vertex and CRISPR Therapeutics Complete Submission of Rolling BLAs to the FDA for exa-cel
Vertex Pharmaceuticals Incorporated and CRISPR Therapeutics have completed the rolling Biologics License Applications (BLAs) to the US Food and Drug Administration (FDA) for the investigational treatment exagamglogene autotemcel (exa-cel) for sickle cell disease (SCD) and transfusion-dependent beta-thalassemia. The BLAs include requests for Priority evaluation, which, if granted, would reduce the FDA’s evaluation of the application to eight months from the time it was submitted, as opposed to the typical review timetable of 12 months. These submissions are backed up by data from two current Phase III investigations, CLIMB-111 and CLIMB-121, as well as a long-term follow-up study, CLIMB-131. Data from the Phase III studies were most recently reported in December 2022 at the American Society of Hematology (ASH) Annual Meeting and Exposition.
The completion of our exa-cel global regulatory filings is a historic milestone. We’d like to thank the clinical trial participants, as well as the sickle cell and beta thalassemia communities, as well as the physicians, nurses, coordinators, caregivers, and friends who have supported them.Carmen Bozic, M.D., Vertex Pharmaceuticals’ Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer.
Within a decade, we went from discovering the CRISPR platform to the first regulatory filings for a CRISPR-based therapy, demonstrating the transformative nature of CRISPR technology”Phuong Khanh (P.K.) Morrow, M.D., FACP, Chief Medical Officer at CRISPR Therapeutics
Exa-cel has received FDA designations for Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease in the United States for both SCD and TDT. In Europe, exa-cel Marketing Authorization Applications (MAAs) were submitted in December 2022 and validated in January 2023 by the European Medicines Agency (EMA) and the Medicines and Healthcare Products Regulatory Agency (MHRA). Exa-cel has received an Orphan Drug classification from the European Commission, as well as Priority Medicines (PRIME) classification from the European Medicines Agency (EMA) for both SCD and TDT. The MHRA has also given exa-cel an Innovation Passport under the Innovative Licensing and Access Pathway (ILAP) in the United Kingdom.
Cingulate Completes First Cohort of Phase 3 Adult Onset and Duration Trial of CTx-1301 (dexmethylphenidate) for ADHD
On April 04, 2023, Cingulate Inc. (NASDAQ: CING) announced it had completed the first cohort of its Phase 3 adult onset and duration trial of its lead candidate, CTx-1301 (dexmethylphenidate), for attention deficit/hyperactivity disorder (ADHD). The Phase 3 CTx-1301-022 study (NCT05631626) assesses the onset and duration of CTx-1301 in up to 25 adults (age range: 18-55 years) with ADHD in an adult laboratory classroom setting. The study consists of a screening period, a five-week dose-optimization phase, a double-blind, randomized phase, and a seven-day safety follow-up period. Results from the trial are expected in 3Q 2023.
Cingulate’s lead candidate, CTx-1301, utilizes the Company’s proprietary PTR drug delivery platform to create a breakthrough, multi-core formulation of the active pharmaceutical ingredient dexmethylphenidate, a compound approved by the FDA for the treatment of ADHD. Dexmethylphenidate is part of the stimulant class of medicines and increases norepinephrine and dopamine activity in the brain to affect attention and behavior.
The first Phase 3 study (CTx-1301-022, NCT05631626) for CTx-1301 is a single-center, dose-optimized, double-blind, randomized, placebo-controlled, parallel efficacy and safety adult laboratory classroom (ALC) study with CTx-1301 in up to 25 adults (age range: 18–55 years) with ADHD. The study will comprise a screening period, a dose-optimization phase, a double-blind, randomized phase, and a seven-day safety follow-up period. Subjects will undergo a screening visit prior to entering a five-week dose-optimization phase.
“We’re pleased with the speed in which our first cohort of this Phase 3 trial was able to be completed, underscoring the ADHD community’s interest in new stimulant treatment options and affirming our goal of having full trial results by third quarter 2023. There is a large and growing population of adults with ADHD who with appropriate diagnosis stand to benefit from effective entire active-day efficacy, and we’re confident that an optimized version of the already-established active ingredient in CTx-1301, dexmethylphenidate, could be an important addition to the $22 billion ADHD market.” –Shane J Schaffer, Chairman and CEO, Cingulate
“Along with eight dosing strengths to best optimize patient’s unique dosing needs, the CTx-1301 clinical profile and proprietary tablet design stand to effectively eliminate the need for short-acting booster doses that are prescribed to over 60 percent of patients, and which are a primary source of non-compliance, abuse and misuse of these medicines.”Matthew Brams, MD, Chief Medical Officer, Cingulate
The Phase 3 clinical trial program for CTx-1301 will be conducted in the U.S. and is instrumental for the filing of the NDA to the FDA, expected in the first half of 2024. As per the update, the company has initiated the first of two Phase 3 clinical studies of CTx-1301 to support its NDA submission. The pivotal, Phase 3 fixed-dose trial in children and adolescents is scheduled to begin in mid-2023.
In addition to the Phase 3 adult dose-optimization study, Cingulate plans to commence its pivotal Phase 3 fixed-dose pediatric and adolescent study in mid-2023. Assuming positive clinical results from the Phase 3 trials, Cingulate plans to submit a New Drug Application (NDA) for CTx-1301 in the first half of 2024 under the Section 505(b)(2) pathway.
ADHD is a chronic neurobiological and developmental disorder that affects millions of children and often continues into adulthood. As per DelveInsight’s analysis, among the 7MM, the US had the highest number of cases, followed by Japan and other European countries. In the US, about 6.4 million children and adolescents (11 percent) under 18 have been diagnosed with ADHD.
Similarly, among the European countries (EU5), France had the highest diagnosed prevalent population of ADHD, with 2,387,000+ cases, followed by Italy in 2017. On the other hand, Germany had the lowest diagnosed prevalent population in 2017. While Japan had 3,138,000+ diagnosed prevalent cases of ADHD in 2017. Globally, several companies are active in the ADHD therapeutics market. The ongoing clinical trial activities anticipate high hope for a better treatment option for the affected patients.
Nuance Pharma Announces Dosing of First Patient in ENHANCE – China Phase III Trial for Chronic Obstructive Pulmonary Disease
On April 6, 2023, Nuance Pharma (“the Company”) announced the dosing of the first patient in the ENHANCE – China Phase III Trial for the maintenance treatment of chronic obstructive pulmonary disease (“COPD”) of its novel solution Ensifentrine (RPL554) in mainland China. Nuance’s Ensifentrine is an investigational first-in-class, selective, dual inhibitor of the enzymes phosphodiesterase 3 and 4 (“PDE3” and “PDE4”), combining bronchodilator and non-steroidal anti-inflammatory activities in one compound. This activity has the potential to alleviate respiratory symptoms such as breathlessness and cough, as well as provide anti-inflammatory benefits for those with COPD.
As per the update, in Phase II clinical studies in COPD, ensifentrine has shown significant and clinically meaningful improvements in lung function, symptoms, and quality of life as monotherapy or added onto a maintenance bronchodilator. In the Phase III ENHANCE-1 and ENHANCE-2 clinical trials, ensifentrine showed significant and clinically meaningful improvements in lung function measures and reduced the rate of COPD exacerbations. Ensifentrine has been well tolerated in clinical trials involving approximately 3,000 subjects to date.
Key Development and Timeline of Ensifentrine Study in China
- April 6th, 2023, Nuance Pharma announces the first COPD patient dosed in the ENHANCE – CHINA Phase III trial (RPL554 – CPC001; NCT05743075), a randomized, double-blind, placebo-controlled clinical study to evaluate the efficacy and safety of Ensifentrine over 24 weeks in patients with moderate to severe COPD.
- March 9th, 2023, Nuance Pharma completed the first dosing of the first healthy subject in the Phase I trial (RPL554 – AHC001; NCT05758428), a PK, safety, and tolerability study of nebulized Ensifentrine on healthy Chinese volunteers.
- On August 17th, 2022, Nuance Pharma announced the IND approval from the Center for Drug Evaluation (CDE) for supporting its pivotal Phase I and Phase III clinical trials of Ensifentrine in the maintenance treatment of COPD.
Earlier on December 20th, 2022, Nuance’s global partner Verona Pharma announced Ensifentrine met primary and key secondary endpoints in Phase III ENHANCE-1 trial for COPD after a positive readout for Phase III ENHANCE-2 trial for COPD in August 2022, another step closer to providing a much-needed novel therapy for COPD patients. Verona Pharma plans to submit a New Drug Application to the US Food and Drug Administration in the second quarter of 2023.
It gives me great pleasure to announce the first dosing of ENHANCE-China Phase III trial. This represents a crucial milestone for our collaboration with Verona Pharma and is indicative of a strong opening to the China clinical development program. Ensifentrine combines bronchodilator and non-steroidal anti-inflammatory properties in one compound, differentiating it from existing drug classes used to treat COPD. We are looking forward to introducing this novel drug in Greater China to address unmet needs in the COPD market.Mark G. Lotter, CEO, and Co-Founder of Nuance Pharma.
As per DelveInsight, The diagnosed prevalence of COPD in the 7MM was 34,640,000+ in 2020, the cases are expected to increase in the coming years. The estimates suggest a higher diagnosed prevalence of COPD in the United States, with 17,455,000+ diagnosed cases in 2020. Germany has the highest diagnosed prevalent population among the five major European countries, followed by Italy and France. On the other hand, Spain had the lowest diagnosed prevalent population. Currently, several major companies are actively working in the COPD therapeutics market to improve the treatment scenario. Some of the drugs are in the advanced stage of clinical trial and are expected to hit the market in the near future.