FDA Approves RINVOQ as a Once-Daily Pill for Moderately to Severely Active Crohn’s Disease

AbbVie announced that the FDA had approved RINVOQ® (upadacitinib) for treating people with moderately to highly active Crohn’s disease who have had an unsatisfactory response or intolerance to one or more TNF blockers. This is RINVOQ’s sixth FDA approval in rheumatology, dermatology, and gastroenterology, which is now indicated in ulcerative colitis and Crohn’s disease.

Crohn’s disease is a chronic, systemic disease characterized by inflammation of the gastrointestinal (or digestive) tract, resulting in persistent diarrhea and abdominal pain. It is a progressive disease, which means it worsens over time and, in many cases, necessitates surgery. As Crohn’s disease’s signs and symptoms are unpredictable, it places a considerable burden on those who live with the disease.

“AbbVie recognises the need for more Crohn’s disease treatment options that can help address both rapid symptom relief and visible reduction of intestinal lining damage,” said Thomas Hudson, M.D., senior vice president of research and development and chief scientific officer at AbbVie. “We’re pleased that RINVOQ may provide this relief and that it is now available to treat Crohn’s disease.”

“Symptoms of moderately to severely active Crohn’s disease can be disruptive and uncomfortable for patients, so getting relief as soon as possible is critical.” Given the disease’s progressive nature, the endoscopic response is equally as crucial,” said Edward V. Loftus, Jr., M.D., professor of medicine in the division of gastroenterology and hepatology at Mayo Clinic in Rochester, Minnesota, and U-EXCEL research investigator. “Based on the clinical trial results, treatment with RINVOQ provides both immediate and long-term symptom relief, as well as evidence of a visible reduction in damage to the intestinal lining caused by excess inflammation.”

The RINVOQ approval is based on results from two induction trials, U-EXCEED and U-EXCEL, as well as the U-ENDURE maintenance study. Statistical significance was established for the co-primary objectives and critical secondary endpoints with RINVOQ 45 mg in the induction studies and RINVOQ 15 mg and 30 mg in the maintenance study when compared to placebo.

FDA Approves Krystal Biotech’s Gene Therapy Vyjuvek for Dystrophic Epidermolysis Bullosa

Krystal Biotech, Inc. announced that the US Food and Drug Administration (FDA) has approved VYJUVEKTM (beremagene geperpavec-svdt) for the treatment of dystrophic epidermolysis bullosa (DEB) in patients aged six months and older. VYJUVEK is intended to treat the genetic root cause of DEB by delivering functional copies of the human COL7A1 gene, resulting in wound healing and sustained functional COL7 protein expression with redosing. VYJUVEK is the first and only FDA-approved drug for the treatment of DEB, both recessive and dominant, that can be administered by a healthcare professional in either a healthcare professional setting or at home.

“This is a devastating disease,” stated M. Peter Marinkovich, M.D., the GEM-3 trial’s principal investigator, Director of the Blistering Condition Clinic at Stanford Health Care, and Associate Professor of Dermatology at Stanford University School of Medicine. “Until now, doctors and nurses had no way of preventing blisters and wounds from developing on the skin of dystrophic EB patients, and all we could do was bandage them and helplessly watch as new blisters formed.” VYJUVEK topical gene therapy alters everything. Because it corrects the underlying skin deficiency of dystrophic EB, VYJUVEK both cures patient wounds and prevents skin from re-blistering. Because it is safe and simple to apply directly to wounds, it does not necessitate a lot of supporting technology or specialized skills, making VYJUVEK extremely accessible even to patients who live distant from specialized centers.”

VYJUVEK was approved by the FDA based on two clinical investigations. The GEM-I/II trial was an intra-patient, open-label, single-center, randomized, placebo-controlled study that found that repeat topical applications of VYJUVEK were associated with long-term wound closure, full-length cutaneous COL7 expression, and anchoring fibril assembly with few adverse events. The GEM-3 experiment was an intra-patient, double-blind, multicenter, randomized, placebo-controlled study that fulfilled both its primary and secondary endpoints of full wound healing at six months and three months. VYJUVEK was well tolerated, with no drug-related major adverse events or treatment-related discontinuations.

VYJUVEK will be accessible in the United States in the third quarter of 2023, and the Company will begin marketing it immediately. Krystal Connect, a personalized support program, was designed by the Company to fulfill the needs of patients, carers, and families as they begin and continue their VYJUVEK treatment journey.

FDA Approves EPKINLY as the First and Only Bispecific Antibody to Treat Adult Patients with R/R DLBCL

AbbVie announced that the U.S. Food and Drug Administration (FDA) has given its approval for EPKINLYTM, the first and only T-cell engaging bispecific antibody, as a treatment for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). This approval applies to DLBCL cases not otherwise specified, including those arising from indolent lymphoma, and high-grade B-cell lymphoma, after two or more rounds of systemic therapies. EPKINLY has been granted approval under the FDA’s Accelerated Approval program based on its response rate and durability of response. However, the continued approval for this indication may be subject to verification and description of clinical benefits in confirmatory trials. The development of EPKINLY is a collaborative effort between AbbVie and Genmab as part of their oncology partnership.

DLBCL is an aggressive type of non-Hodgkin’s lymphoma characterized by fast growth and affecting B cells in the lymphatic system. It is the most common form of non-Hodgkin’s lymphoma, with an estimated 30,400 cases in the United States in 2022 and 150,000 new cases worldwide annually. DLBCL patients are typically treated with chemoimmunotherapy-based regimens, but options for patients who have relapsed or are refractory to current therapies are limited. Recent advancements in targeted therapies, including T-cell-mediated treatments, have emerged as potential options for these patients.

AbbVie is dedicated to transforming standards of care for blood cancers and advancing cancer research and treatment. EPKINLY is the third approved blood cancer treatment in AbbVie’s growing oncology portfolio, reflecting their commitment to making a significant impact on the lives of people living with cancer.

FDA Grants Orphan Drug Designation to Mitazalimab in Pancreatic Cancer

Alligator Biosciences, a drug developer, has announced that the U.S. The Food and Drug Administration has granted orphan drug designation to mitazalimab for its potential use as a therapeutic option in patients with pancreatic cancer. Mitazalimab is a monoclonal antibody that targets CD40 and is designed to sensitize tumors to chemotherapy and stimulate immune-mediated cell death by activating dendritic cells, B cells, and macrophages. Its safety and effectiveness, in combination with modified FOLFIRINOX, are currently being evaluated in treatment-naïve patients with metastatic pancreatic ductal adenocarcinoma as part of the OPTIMIZE-1 trial, a phase 2 multicenter study.

Søren Bregenholt, the CEO of Alligator Bioscience, expressed his excitement over the orphan drug designation, considering it a significant milestone for mitazalimab, which has shown promising clinical results in its phase 2 trial for pancreatic cancer. Bregenholt explained that the orphan designation provides important benefits, such as cost savings during development and marketing exclusivity following approval, and he is pleased to see the potential of mitazalimab being recognized through this designation.

In January 2023, Alligator Biosciences reported positive interim data from the OPTIMIZE-1 trial, indicating that the addition of mitazalimab to mFOLFIRINOX resulted in an objective response rate (ORR) of 52% and a disease control rate of over 90% in 23 evaluable patients, based on RECIST v1.1 criteria. Furthermore, the combination treatment was found to be safe and well-tolerated at the recommended dose of 900 μg/kg during the phase 1b dose-escalation phase of the trial.

The early efficacy findings from the OPTIMIZE-1 trial are promising when compared to the results of a previous phase 3 trial (NCT00112658), where FOLFIRINOX alone achieved an ORR of 31.6% as a frontline therapy for patients with metastatic pancreatic cancer.

Alligator Biosciences announced in April 2023 that the OPTIMIZE-1 trial had been fully enrolled. To be eligible for the study, patients had to be at least 18 years old, have a diagnosis of previously untreated metastatic pancreatic ductal adenocarcinoma, and have a life expectancy of at least 3 months. Patients were also required to have acceptable hematologic and clinical chemistry laboratory values and should not have received prior chemotherapy or abdominal radiotherapy.

The primary endpoints of the OPTIMIZE-1 trial are the frequency of dose-limiting toxicities and the ORR. Secondary endpoints include progression-free survival, overall survival, and safety, among others.

Additional interim data, including results on progression-free survival, are expected in mid-2023, and full topline data are anticipated in the first quarter of 2024. These data, combined with the orphan drug designation, will facilitate ongoing discussions with the FDA regarding further clinical development and the approval pathway for mitazalimab in the treatment of pancreatic cancer.

Oculis Announces Positive Top-Line Results from DIAMOND Stage 1 Phase 3 Trial in Diabetic Macular Edema with OCS-01 Eye Drops

On May 22, 2023, Oculis Holding AG (Nasdaq: OCS) (“Oculis”) announced positive top-line results from Stage 1 of its Phase 3 DIAMOND trial of OCS-01 eye drops in Diabetic Macular Edema (DME). OCS-01 Positive Phase 3 Stage 1 Top Line Results Could Signify a Paradigm Shift in Diabetic Macular Edema Treatment.

DIAMOND (DIAbetic Macular edema patients ON a Drop) is a Phase 3, two-stage, double-masked, randomized, multicenter trial to assess the efficacy and safety of OCS-01 eye drops in DME patients. The primary objective of Stage 1 was to select the optimal dosing regimen. Stage 1 was conducted in 39 sites across the USA and Europe, with 148 patients randomized 2:1 to receive OCS-01 (n=100) or vehicle (n=48) six times daily for a six-week loading phase and then three times daily for a subsequent six-week maintenance phase.

OCS-01, in this 3-month trial, has met both clinical efficacy endpoints (main BCVA change, proportion of patients with 3 lines gain) that are required for regulatory approval, if met at 12 months treatment duration. OCS-01 was well-tolerated, with no unexpected adverse events observed. The OCS-01 development program will continue as planned with Stage 2 which includes two global trials, each enrolling approximately 350–450 patients. Oculis expects to begin Stage 2 of the DIAMOND trial in the second half of this year.

I am pleased and very encouraged that in Stage 1 of this trial, OCS-01 has met both primary and secondary endpoints in a robust and statistically significant manner. A topical agent has never demonstrated a positive result in DME. Now, OCS-01 has been validated in two different studies with consistent and repeated positive results. We remain focused on advancing with high priority the DIAMOND Phase 3 trial to Stage 2. This important milestone has the potential to bring us one step closer to providing the first treatment in the form of eye drops to patients with DME which is a devastating and blinding disease.

Riad Sherif, M.D., CEO of Oculis

The mechanism of DME involves both increased permeability and inflammation. Current anti-VEGFs are effective as anti-permeability agents but have no effect on inflammation. Therefore, a significant proportion of patients are sub-optimally treated with anti-VEGFs alone. If approved, OCS-01 has the potential to complement current treatment and address recalcitrant patients. Furthermore, since it is a topical agent, it has also the potential to be a first line treatment in DME, if approved. In short, I believe the impact of OCS-01 in DME could be a true game-changer.

David S. Boyer, M.D., Adjunct Clinical Professor of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles and Co-Principal Investigator for the DIAMOND trial

As per DelveInsight, Diabetic Macular Edema is the leading cause of visual loss and legal blindness in patients with diabetes. Globally, about 37 million people worldwide, with a significant number of patients left untreated due to a lack of convenient treatment options. Among the 7MM, the total prevalent cases of Diabetic Macular Edema (DME) were the highest in the US  in 2021, with more than 1 million cases, and lowest in France with 60,000 cases. Moreover, Japan accounted for approximately 194,000 cases in 2019, which is nearly 11% of the total DME prevalent cases in the 7MM. The rising cases of Diabetic Macular Edema are driving the demand for effective and safe vaccines. The emerging pipeline therapies, anticipated high hope for better treatment scenarios in the coming years.

TAGRISSO® (osimertinib) + Chemotherapy Exhibited Strong Improvement in Progression-free Survival for Patients with EGFR-mutated Advanced Lung Cancer

On May 17, 2023, AstraZeneca announced FLAURA2 Phase III trial result for TAGRISSO® (osimertinib) plus chemotherapy demonstrated strong improvement in progression-free survival for patients with epidermal growth factor receptor-mutated (EGFRm) advanced lung cancer. TAGRISSO® (osimertinib) in combination with chemotherapy demonstrated a statistically significant and clinically meaningful result compared to TAGRISSO alone for patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) EGFRm Non-small cell lung cancer (NSCLC)

As the global standard of care for EGFR-mutated non-small cell lung cancer, osimertinib monotherapy has transformed the treatment landscape, allowing many patients the opportunity to achieve improved survival. FLAURA2 provides compelling evidence that the addition of chemotherapy to osimertinib can provide a new option for patients and clinicians that further improves outcomes compared to osimertinib alone and, as such, can further delay treatment resistance and disease progression. 

Pasi A. Jänne, MD, PhD, medical oncologist at Dana-Farber Cancer Institute and principal investigator for the FLAURA2 trial,

These significant FLAURA2 results show TAGRISSO has the potential to offer patients in the first-line setting a new treatment option that can extend the time they live without their disease progressing. This meaningfully builds on successive trials demonstrating improved clinical benefit with TAGRISSO in patients with EGFR-mutated lung cancer.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca

Safety results and discontinuation rates due to adverse events were consistent with the established profiles of each medicine. At the time of this analysis, the overall survival (OS) data were immature and will be formally assessed at a subsequent analysis. As per the update, AstraZeneca is expected to present data at a forthcoming medical meeting and shared it with global health authorities.

As part of AstraZeneca’s ongoing commitment to treating patients as early as possible in lung cancer, TAGRISSO is also being investigated in unresectable NSCLC in the pivotal LAURA Phase III trial, with results expected later this year.

About 2.2 million people are diagnosed with lung cancer globally. As per the latest market assessment by DelveInsight, the United States had 227,000+ incident cases of Lung Cancer in 2020, of which ~85%, i.e., 193,694 were NSCLC cancer patients. Among the European 5 countries, Germany had the highest cases of NSCLC. Furthermore, Japan accounts for about 117,000+ cases in 2020. Among the 7MM, the highest number of NSCLCs were estimated in the United States. Additionally, about 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.