The estimated number of individuals diagnosed with biliary tract cancer in Japan is around 25,000. The cancer has a five-year survival rate of approximately 25%, positioning it as a challenging condition with the second-worst prognosis, surpassed only by pancreatic cancer. Limited drug therapy options exist for this type of cancer, indicating significant unmet medical needs. In intrahepatic cholangiocarcinoma, a subtype constituting 15-30% of biliary tract cancers, approximately 14% of cases exhibit FGFR2 gene fusion. FGFR genetic aberrations, including gene fusions, play a crucial role in cancer cell proliferation, survival, migration, tumor angiogenesis, and drug resistance.
These genetic abnormalities are not exclusive to biliary tract cancer but are also observed in various other cancer types. Consequently, there is a growing interest in FGFRs as a promising target for cancer therapy. Tasurgratinib, by selectively inhibiting FGFR1, 2, and 3 and disrupting their signals, is anticipated to emerge as a novel molecular targeted therapy for cancers characterized by FGFR genetic aberrations.
CHMP Issues Positive Opinion for Biogen’s SKYCLARYS, the First Therapy to Treat Friedreich’s Ataxia, a Rare Neurodegenerative Disease
Biogen Inc. has revealed that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a recommendation for the marketing authorization of SKYCLARYS (omaveloxolone) for Friedreich’s ataxia (FA) treatment in individuals aged 16 years and above. Should the European Commission (EC) grant approval, SKYCLARYS would become the inaugural authorized treatment for this uncommon genetic neuromuscular ailment within the European Union. In the event of approval, omaveloxolone will be commercially available under the brand name SKYCLARYS.
The CHMP’s recommendation of SKYCLARYS marks a significant achievement in our mission to provide a treatment that hinders the advancement of FA to patients in the region,” stated Dr. Priya Singhal, Head of Development at Biogen. “With the approval of SKYCLARYS, we anticipate utilizing Biogen’s rare disease knowledge and resources to introduce this innovative treatment to individuals in the European Union grappling with this incapacitating condition.
The favorable recommendation from the CHMP for SKYCLARYS is grounded in the effectiveness and safety findings derived from the placebo-controlled MOXIe Part 2 trial. Upon concluding the 48-week MOXIe Part 2 study, individuals administered SKYCLARYS exhibited reduced physical impairment in comparison to those given a placebo, as assessed by the modified Friedreich Ataxia Rating Scale (mFARS). Patients treated with SKYCLARYS also demonstrated enhancements across various mFARS subscales, encompassing upright stability, lower limb coordination, ability to swallow, and upper limb coordination, in contrast to those receiving a placebo. Supplementary data, stemming from a post hoc, propensity-matched analysis, revealed that individuals treated with SKYCLARYS in both MOXIe Parts 1 and 2 exhibited lower mFARS scores at the 3-year mark when compared to a matched natural history group. Common adverse effects include heightened liver enzymes, reduced weight and appetite, nausea, vomiting, diarrhea, headache, fatigue, oropharyngeal and back pain, muscle spasms, and influenza.
The recommendation for SKYCLARYS from CHMP will undergo a review by the European Commission (EC) for marketing authorization within the European Union. The final decision is anticipated in the first quarter of 2024. In February 2023, the FDA approved omaveloxolone, sold under the brand name SKYCLARYS, to treat Friedreich’s ataxia in adults and adolescents aged 16 years and older.
European Commission Approves Merck’s KEYTRUDA Plus Chemotherapy for New First-Line Indications in Advanced HER2-Negative Gastric or GEJ Adenocarcinoma in Tumors Expressing PD-L1 (CPS ≥1) and Advanced Biliary Tract Cancer
Merck & Co. has received the green light from the European Commission to expand the use of KEYTRUDA, its anti-PD-1 therapy, in gastrointestinal cancers. The approvals encompass two new indications:
- KEYTRUDA in combination with fluoropyrimidine- and platinum-containing chemotherapy is now approved as a first-line treatment for locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma in adults whose tumors express PD-L1 with a Combined Positive Score (CPS) ≥1.
- KEYTRUDA in combination with gemcitabine and cisplatin is now indicated as a first-line treatment for locally advanced unresectable or metastatic biliary tract carcinoma (BTC) in adults.
These approvals follow positive recommendations from the Committee for Medicinal Products for Human Use, which were based on data from the Phase 3 trials KEYNOTE-859 and KEYNOTE-966, demonstrating improved overall survival.
In KEYNOTE-859, the combination of KEYTRUDA and chemotherapy significantly enhanced OS across the patient population, reducing the risk of death by 22%. Notably, in patients with PD-L1-expressing tumors (CPS ≥1), the risk of death decreased by 26%. Similarly, KEYNOTE-966 showed a statistically significant 17% reduction in the risk of death when using KEYTRUDA plus chemotherapy compared to chemotherapy alone.
Dr. Marjorie Green, senior vice president and head of late-stage oncology at Merck Research Laboratories, highlighted the significance of these approvals, emphasizing KEYTRUDA’s potential across various gastrointestinal cancers. These recent approvals mark the seventh and eighth indications in this domain.
The safety profile of KEYTRUDA plus chemotherapy was assessed across various tumor types. In both trials, adverse reactions of Grade 3-5 were reported, with a slightly higher incidence in patients receiving the combination therapy.
These approvals allow for the marketing of these KEYTRUDA regimens in all 27 EU member states, as well as Iceland, Liechtenstein, Norway, and Northern Ireland. With these additions, KEYTRUDA now boasts approval for 26 indications in the EU, with seven related to gastrointestinal cancers.
Merck continues its extensive clinical development program to evaluate KEYTRUDA’s efficacy across various gastrointestinal cancers and is dedicated to exploring multiple uses in gastric cancer, hepatobiliary cancer, esophageal cancer, and colorectal cancer.
Bristol Myers Squibb Provides Update on RELATIVITY-123 Trial Evaluating the Fixed-Dose Combination of Nivolumab and Relatlimab in Patients with Previously Treated Metastatic Microsatellite Stable Colorectal Cancer
Bristol Myers Squibb has announced the discontinuation of the Phase 3 RELATIVITY-123 trial, which was assessing the fixed-dose combination of nivolumab and relatlimab for treating microsatellite stable metastatic colorectal cancer (mCRC) in patients whose disease had progressed after one to four prior lines of therapy for metastatic disease. An independent data monitoring committee conducted a planned analysis and concluded that the trial would unlikely achieve its primary endpoints.
The decision to halt the study was not due to safety concerns, as the safety profile aligned with previously reported studies of the nivolumab and relatlimab combination. However, the trial was deemed unlikely to meet its specified goals upon completion.
The exploration of the nivolumab and relatlimab combination for treating other tumor types will continue as originally planned. These findings do not impact the current approval for patients with unresectable or metastatic melanoma.
Dr. Jeffrey Walch, the vice president and global program lead at Bristol Myers Squibb, acknowledged the challenges in treating metastatic colorectal cancer, particularly in patients with microsatellite stable (MSS) tumors who have limited options in later lines of therapy. Although immunotherapies historically showed limited efficacy in MSS colorectal cancers, there was hope for substantial clinical benefits in this patient group. Dr. Walch expressed disappointment in the trial’s outcome but reaffirmed the company’s commitment to developing immune-oncology therapies, such as Opdivo (nivolumab) and Yervoy (ipilimumab), for patients with microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) colorectal cancers.
The company plans to provide the trial’s data to investigators so they can determine appropriate steps for patients enrolled in RELATIVITY-123. A comprehensive evaluation of the data will be conducted, and collaboration with investigators aims to share the results within the scientific community.
Kyverna Therapeutics Granted FDA Fast Track Designation for KYV-101 in the Treatment of Patients With Refractory Myasthenia Gravis
On Dec. 13, 2023, Kyverna Therapeutics, Inc. (Kyverna) disclosed that its autologous, entirely human CD19 chimeric antigen receptor (CAR) T-cell product candidate, KYV-101, has received Fast Track Designation from the U.S. Food and Drug Administration (FDA). This designation is specifically for employing KYV-101 in treating Myasthenia Gravis (MG).
CAR T-cell therapy entails altering a patient’s T cells to identify and eliminate B cells within the patient’s system. Kyverna’s CD19 CAR T-cell therapy, known as KYV-101, precisely homes in on CD19, a protein present on B cells’ surfaces, a pivotal component in numerous autoimmune conditions. Kyverna aims to further investigate additional applications for KYV-101 and construct a strong portfolio of promising immunotherapy candidates to address the untreated medical requirements in autoimmune diseases.
We are very happy to receive this important designation for KYV-101 in the KYSA-6 trial and remain committed to improving the lives of patients living with severe and debilitating neurological autoimmune diseases,” said Peter Maag, Ph.D., chief executive officer of Kyverna. “This is the second time KYV-101 has received such designation, after obtaining the first one for lupus nephritis earlier this year.
At present, Kyverna is actively engaged in two trials involving KYV-101 among individuals afflicted by lupus nephritis, an autoimmune ailment where over half of patients don’t attain full recovery with existing treatments, facing the risk of kidney failure. Preparations for further clinical trials of KYV-101 targeting systemic sclerosis, myasthenia gravis, and multiple sclerosis are underway.
Myasthenia gravis, an autoimmune condition, results in muscle weakness affecting various body tissues. This weakness can lead to partial paralysis of eye movements, difficulties in chewing, swallowing, and breathing, speech impairments, and skeletal muscle weakness. Patients with Myasthenia Gravis develop antibodies, triggering an immune attack on crucial signaling proteins at the junction between nerve and muscle cells. This attack disrupts nerve-muscle communication. Initially, symptoms may be fleeting, and in the early stages, they might spontaneously subside. However, as the disease advances, symptom-free intervals lessen, and exacerbations can persist for months. In about 80% of patients, the disease peaks within two to three years, while up to 20% may encounter respiratory crises at least once during their lives.
Pharmaceutical companies are addressing treatment challenges in the Myasthenia gravis therapeutics market by pioneering innovative therapies that target the immune system’s malfunction and developing personalized treatment approaches to manage symptoms and improve patients’ quality of life.
Verrica Pharmaceuticals and Torii Pharmaceutical Announces Positive Top-line Results from a Confirmatory Phase 3 Trial of TO-208 for the Treatment of Molluscum Contagiosum in Japan
On December 15, 2023, Verrica Pharmaceuticals Inc. (“Verrica” or “the Company”) (Nasdaq: VRCA) announced that its collaborator in development and commercialization, Torii Pharmaceutical Co., Ltd. (“Torii”), had reported encouraging top-line outcomes from the Phase 3 trial of TO-208 (known as VP-102 and marketed as YCANTH™ in the U.S.) designed for the Molluscum Contagiosum (“molluscum”) treatment in Japan.
Conducted in Japan, the Phase 3 trial adopted a double-blind, randomized, parallel-group comparison study aimed to assess TO-208’s efficacy and safety compared to a placebo. Administered once every 21 days for up to four applications in molluscum patients, the top-line findings revealed a statistically significant proportion of subjects achieving complete clearance of treatable molluscum lesions—meeting the primary efficacy endpoint of the confirmatory study—compared to the placebo. Throughout the study, TO-208 demonstrated good tolerability.
Earlier in March 2021, Verrica and Torii inked an exclusive licensing deal for VP-102’s development and commercialization in Japan. Leveraging the Phase 3 trial outcomes and ongoing studies, Torii plans to file a manufacturing and marketing application for the product in Japan.
We are obviously excited by the positive results from this confirmatory Phase 3 trial for TO-208 for the treatment of molluscum in Japan, which underscores the consistent safety and efficacy of VP-102 and FDA-approved YCANTH,” said Ted White, Chief Executive Officer of Verrica Pharmaceuticals. “We believe Torii is an ideal partner to bring the product to people with molluscum in Japan, and these positive results take us one step closer towards achieving our goal of addressing this large and underserved patient population.
Molluscum Contagiosum, a common viral skin infection caused by the Molluscum Contagiosum virus, presents a substantial burden, particularly among children and individuals with compromised immune systems. Molluscum Contagiosum Virus (MCV) is one of the 50 most frequent diseases worldwide. Molluscum Contagiosum is characterized by small, raised, painless bumps on the skin’s surface, often appearing in clusters and ranging in number from a few to several dozen.
As per DelveInsight, in 2021, among the 7MM, the US had the highest number of prevalent cases of Molluscum Contagiosum (MC) with around 6,250,000 cases and the lowest was in Spain with ~680,000 cases. Among EU5 countries, France had the highest number of prevalent cases of Molluscum Contagiosum (MC) (around 1.3 million cases) in 2021. In 2021, Japan had about 1,330,000 prevalent cases of Molluscum Contagiosum (MC). Moreover, Japan had about 800k males compared to nearly 530,000 females suffering from Molluscum Contagiosum (MC) in 2021.
Pharmaceutical companies are actively addressing the challenges posed by Molluscum Contagiosum. The development and advancement of therapies like VP-102 (marketed as YCANTH™ in the U.S.) by companies such as Verrica Pharmaceuticals (Torii Pharmaceutical) represent a significant stride in managing this condition. These innovations aim to provide safe, effective, and patient-friendly treatment alternatives, countering the limitations of traditional therapies, which often involve invasive procedures or therapies with potential side effects.
The Phase 3 trial results of TO-208 (VP-102/YCANTH™) conducted in Japan, showcasing promising outcomes in achieving complete clearance of treatable molluscum lesions, offer hope for individuals seeking better treatment options. Torii’s intent to pursue regulatory approval based on these findings and additional ongoing studies demonstrates a commitment to addressing the unmet medical needs associated with Molluscum Contagiosum.
