FDA Accepts IND Application for MERKLIN 2 Study
Planegg-Martinsried, Germany, 8 April 2020 – 4SC AG (4SC, FSE Prime Standard: VSC) today announced that its Investigational New Drug (IND) application for domatinostat in combination with avelumab (Bavencio®) has been accepted by the U.S. Food and Drug Administration (FDA). The MERKLIN 2 study is a Phase II clinical study evaluating domatinostat in combination with avelumab in patients with advanced MCC whose disease has progressed on anti-PD-(L)1 antibody therapy. Avelumab is an anti-PD-L1 antibody co-developed and co-commercialized by Merck KGaA, Darmstadt, Germany and Pfizer.
MCC is a relatively rare, but highly aggressive and immunogenic type of non-melanoma skin cancer. In 2017, avelumab was the first anti-PD-(L)1 antibody approved in both the EU and US for treatment of metastatic MCC. Since 2017, anti-PD-(L)1 antibodies have become the standard of care in metastatic MCC globally. However, a majority of patients may become refractory or relapse on this treatment, and currently do not have access to effective subsequent therapeutic options, which is reflected by a high mortality rate. The MERKLIN 2 study seeks to address this high unmet medical need.
Jason Loveridge, Ph.D., CEO of 4SC: “We are delighted to be working with Merck KGaA, Darmstadt, Germany and Pfizer as pioneers of immune checkpoint blockade to address the high unmet medical need in patients with advanced MCC disease and now that our IND is open, we can go forward with this study in the US as soon as practically possible”.
4SC AG is a clinical-stage biopharmaceutical company developing small-molecule drugs that can target key indications in cancer with high unmet medical needs. 4SC’s pipeline is protected by a comprehensive portfolio of patents and currently comprises two drug candidates in clinical development: resminostat and domatinostat.
4SC aims to generate future growth and enhance its enterprise value by entering into partnerships with pharmaceutical and biotech companies and/or the eventual marketing and sales of approved drugs in select territories by 4SC itself.
4SC is headquartered in Planegg-Martinsried near Munich, Germany. The Company had 44 employees as of 31 December 2019 and is listed on the Prime Standard of the Frankfurt Stock Exchange (FSE Prime Standard: VSC; ISIN: DE000A14KL72).
Domatinostat is an orally administered small molecule Class I selective HDAC inhibitor with a unique mode of action that was designed to strengthen the body’s own anti-tumor immune response. Domatinostat also influences the tumor microenvironment facilitating infiltration of immune cells into the tumor and making it more visible to the immune system.
Domatinostat has been investigated in a Phase I study with 24 heavily pretreated patients with several types of advanced hematologic cancers and was well tolerated. Positive signs of anti-tumor efficacy were also observed; with one complete remission (28 months) and one partial responder (8 months).
In addition to its therapeutic potential in cancer monotherapy, 4SC is evaluating domatinostat’s capacity as a partner in combination therapies, specifically in the immuno-oncology area. In this respect, 4SC initiated a Phase Ib/II study of domatinostat in combination with the anti-PD-1 checkpoint inhibitor pembrolizumab in patients with advanced-stage melanoma (SENSITIZE) and data from the first part of the study was presented at ESMO in Barcelona. A second Phase II study of domatinostat in combination with the anti-PD-L1 checkpoint inhibitor avelumab in patients with advanced-stage microsatellite-stable gastrointestinal cancer is being conducted by Prof. David Cunningham of The Royal Marsden NHS Foundation Trust, London, UK (EMERGE).
Avelumab Approved Indications
Avelumab (BAVENCIO®) in combination with axitinib is indicated in the US, EU, Japan and other countries for the first-line treatment of patients with advanced renal cell carcinoma (RCC).
The US Food and Drug Administration (FDA) also granted accelerated approval for avelumab (BAVENCIO®) for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.
Avelumab is currently approved for patients with MCC in 50 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.
Avelumab Important Safety Information from the US FDA-Approved Label
The warnings and precautions for avelumab (BAVENCIO®) include immune-mediated adverse reactions (such as pneumonitis and hepatitis [including fatal cases], colitis, endocrinopathies, nephritis and renal dysfunction and other adverse reactions [which can be severe and have included fatal cases]), infusion-related reactions, hepatotoxicity, major adverse cardiovascular events (MACE) [which can be severe and have included fatal cases], and embryo-fetal toxicity.
Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO® monotherapy include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash. Common adverse reactions (reported in at least 20% of patients) in patients receiving BAVENCIO® in combination with axitinib include diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain and headache. Grade 3-4 clinical chemistry and hematology laboratory value abnormalities reported in at least 10% of patients treated with BAVENCIO® monotherapy include hyponatremia, lymphopenia, GGT increased; in patients receiving BAVENCIO® in combination with axitinib, grade 3-4 clinical chemistry and hematology laboratory value abnormalities included blood triglyceride increased and lipase increased.
For full Prescribing Information and Medication Guide for BAVENCIO®, please see www.BAVENCIO.com.
Information set forth in this press release contains forward-looking statements, which involve risks and uncertainties. The forward-looking statements contained herein represent the judgement of 4SC as of the date of this press release. Such forward-looking statements are neither promises nor guarantees but are subject to a variety of risks and uncertainties, many of which are beyond 4SC’s control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. 4SC expressly disclaims any obligation or undertaking to release any updates or revisions to any such statements to reflect any change in its expectations or any change in events, conditions or circumstances on which any such statement is based.