Instant Report

Date: 10-Jul-2019

US FDA Grants Breakthrough Therapy Designation To Bayers Copanlisib To Treat Marginal Zone Lymphoma

Date: 13-Nov-2019

US FDA grants breakthrough therapy designation to F2G's olorofim

F2G Ltd, a UK- and Austria-based biotech company developing novel therapies for life-threatening systemic fungal infections, announced that the US Food and Drug Administration (FDA) has granted breakthrough therapy designation to its lead first-in-class candidate, olorofim (formerly F901318) for the indication of ‘Treatment of invasive mold infections in patients with limited or no treatment options, including aspergillosis refractory or intolerant to currently available therapy, and infections due to Lomentospora prolificans, Scedosporium, and Scopulariopsis species’. Olorofim is the first antifungal agent to be granted Breakthrough Therapy designation. Olorofim is currently being investigated in an open-label single-arm phase 2b study in patients with proven invasive fungal disease (IFD) or probable invasive aspergillosis (IA) and either refractory disease, resistance, or intolerance to available agents. Olorofim has been well tolerated across more than 10 years of patient dosing days with a median therapy duration of 12 weeks. Preliminary data from this study were provided to the FDA as part of the Breakthrough Therapy designation submission. Breakthrough Therapy designation is an FDA process designed to expedite the development and review of drugs that are intended to treat a serious or life-threatening condition and is granted based on preliminary clinical evidence indicating that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. Breakthrough Therapy designation conveys all the features of fast track designation, more intensive FDA guidance on an efficient drug development program, an organisational commitment by FDA to involve senior managers, and eligibility for rolling review and priority review. Commenting on the news, Ian Nicholson, CEO of F2G Ltd, said, “The granting of FDA Breakthrough Therapy designation is a truly transformational step for our company and will support our goal of rapidly developing this novel treatment for patients suffering from serious and life-threatening fungal infections. Olorofim acts via a novel and differentiated mechanism to traditional antifungals, and preliminary data have indicated that it is efficacious in tackling life-threatening invasive fungal infections that cannot be managed with currently approved agents. “Our phase 2b programme is on track with over 40 patients recruited in Europe, Australia and the US. We look forward to working closely with the FDA to accelerate development of this therapy for patients having limited or no approved treatment options for an invasive mold infection.” Professor Sharon Chen, Westmead Hospital Sydney and Principal Investigator for the phase 2b study said, “This news is very exciting for clinicians caring for patients with these very serious, and devastating mold infections. We have had limited treatment options for many years and now the news about olorofim brings realistic hope that we can cure these previously treatment–refractory infections.

Date: 31-Jul-2020

US FDA Grants Breakthrough Therapy Status To Mercks New HIF-2a Inhibitor MK-6482 O Treat Von Hippel-Lindau- Associated Renal Cell Carcinoma

Merck announced that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to the hypoxia-inducible factor-2 alpha (HIF-2a) inhibitor MK-6482, a novel investigational candidate in Merck’s oncology pipeline, for the treatment of patients with von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC)with nonmetastatic RCC tumors less than three centimeters in size, unless immediate surgery is required. The FDA also granted orphan drug designation to MK-6482 for VHL disease. These designations are based on data from a phase 2 trial evaluating MK-6482 in patients with VHL-associated clear cell RCC, which were presented at the 2020 American Society of Clinical Oncology Annual Meeting.

“Merck’s diverse and expansive oncology pipeline is focused on bringing forward innovative new treatments to patients in need and continues to show important progress,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “These designations for MK-6482 support the potential of targeting HIF-2a in certain patients with von Hippel-Lindau disease, who currently have limited treatment options and face an increased risk for benign tumors as well as several types of cancer, including renal cell carcinoma.”

The FDA’s Breakthrough Therapy designation is granted to expedite the development and review of medicines that are intended to treat serious or life-threatening conditions and that have demonstrated preliminary clinical evidence indicating that the medicine may provide a substantial improvement over available therapy on at least one clinically significant endpoint. The FDA’s orphan drug designation is granted to medicines that are intended for the treatment, prevention or diagnosis of rare diseases that affect fewer than 200,000 people in the US.

MK-6482 (formerly PT2977) is an investigational, novel, potent, selective, oral HIF-2a inhibitor that is currently being evaluated in a phase 3 trial in advanced RCC, a phase 2 trial in VHL-associated RCC and a phase 1/2 dose-escalation and dose-expansion trial in advanced solid tumors, including advanced RCC. Proteins known as hypoxia-inducible factors, including HIF-2a, can accumulate in patients when VHL, a tumor-suppressor protein, is inactivated. The accumulation of HIF-2a can lead to the formation of both benign and malignant tumors. This inactivation of VHL has been observed in more than 90% of ccRCC tumors. Research into VHL biology that led to the discovery of HIF-2a was awarded the Nobel Prize in Physiology or Medicine in 2019.

Von Hippel-Lindau disease is a rare genetic disease that affects one in 36,000 people (200,000 cases worldwide and 10,000 cases in the US alone). Patients with VHL disease are at risk for benign blood vessel tumors as well as several cancers, including RCC. As many as 60% of people with VHL disease develop RCC, which is a leading cause of death for patients with VHL disease.

Renal cell carcinoma is by far the most common type of kidney cancer; about nine of 10 kidney cancers are RCCs, and about seven of 10 RCCs are clear cell. Worldwide, it is estimated there were about 403,000 cases of kidney cancer diagnosed and about 175,000 deaths from the disease in 2018. In the US alone, it is estimated there will be nearly 74,000 new cases of kidney cancer diagnosed and almost 15,000 deaths from the disease in 2020

Date: 16-Sep-2020

US FDA Grants Breakthrough Therapy Status To Dupixent To Treat Eosinophilic Esophagitis

Regeneron Pharmaceuticals Inc and Sanofi announced the US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to Dupixent (dupilumab) for the treatment of patients 12 years and older with eosinophilic esophagitis (EoE). The designation for this investigational use is based on positive results from Part A of a phase 3 trial in patients with EoE.

There are currently no US FDA-approved medicines for EoE, a chronic and progressive type 2 inflammatory disease that damages the esophagus and prevents it from working properly. Over time, excessive type 2 inflammation causes scarring and narrowing of the esophagus, making it difficult to swallow. If left untreated, EoE can affect a patient's ability to eat and cause food to become stuck after being swallowed (food impaction), which can lead to a medical emergency. In the US alone, there are approximately 160,000 patients with EoE who are currently being treated with various unapproved therapies or diet modification. Of these patients, approximately 50,000 have failed multiple treatments.

Regeneron and Sanofi previously reported positive results from Part A of the pivotal phase 3 trial evaluating Dupixent in patients 12 years and older with EoE. Part A of the randomized, double-blind, placebo-controlled trial of 81 patients met both of its co-primary endpoints, as well as all key secondary endpoints. Patients treated weekly with Dupixent 300 mg over a 24-week treatment period experienced a reduction in symptoms, esophageal inflammation and abnormal endoscopic findings in the esophagus. The trial demonstrated safety results consistent with the known safety profile of Dupixent in its approved indications. The EoE trial is ongoing, with additional patients enrolling in Part B as well as patients continuing in a 28-week extended active treatment period (Part C) after completing either Part A or Part B.

In 2017, Dupixent also was granted Orphan Drug Designation for the potential treatment of EoE. This is given to investigational medicines intended for the treatment of rare diseases that affect fewer than 200,000 people in the US.

The potential use of Dupixent in eosinophilic esophagitis is currently under clinical development, and its safety and efficacy for this indication have not been evaluated by any regulatory authority.

Dupixent is approved in the US to treat patients aged 6 years and older with moderate-to-severe atopic dermatitis that is not well controlled with prescription therapies used on the skin (topical), or who cannot use topical therapies; for use with other asthma medicines for the maintenance treatment of moderate-to-severe eosinophilic or oral steroid dependent asthma in patients aged 12 years and older whose asthma is not controlled with their current asthma medicines; and for use with other medicines for the maintenance treatment of CRSwNP in adults whose disease is not controlled.

In adolescents 12 years of age or older, it is recommended that Dupixent be administered by or under the supervision of an adult. In children younger than 12 years of age, Dupixent should be administered by a caregiver.

Outside of the US, Dupixent is approved for specific patients with moderate-to-severe atopic dermatitis and certain patients with asthma in a number of other countries around the world, including the EU and Japan. Dupixent is also approved in the EU and Japan to treat certain adults with severe CRSwNP.

Dupixent is a fully-human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) proteins. Data from Dupixent clinical trials have shown that IL-4 and IL-13 are key drivers of the type 2 inflammation that plays a major role in asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP) and atopic dermatitis.

Dupixent was invented using Regeneron'sVelocImmune technology that utilizes a proprietary genetically-engineered mouse platform endowed with a genetically-humanized immune system to produce optimized fully-human antibodies. VelocImmune technology has been used to create multiple antibodies including Libtayo (cemiplimab-rwlc), Praluent (alirocumab) and Kevzara (sarilumab), which are approved in multiple countries around the world. Regeneron previously used these technologies to rapidly develop a treatment for Ebola virus infection, which is currently under review by the FDA, and to create REGN-COV2, a potentially preventative and therapeutic medicine for COVID-19.

To date, dupilumab has been studied in more than 10,000 patients across 50 clinical trials in various chronic diseases driven by type 2 inflammation. Dupilumab is being jointly developed by Regeneron and Sanofi under a global collaboration agreement.

Date: 15-Jan-2021

US FDA Grants Breakthrough Therapy Designation To Novartis’ Ligelizumab To Treat Chronic Spontaneous Urticaria

Novartis announced that the US Food and Drug Administration (FDA) has granted ligelizumab (QGE031) Breakthrough Therapy designation for the treatment of chronic spontaneous urticaria (CSU), also known as chronic idiopathic urticaria (CIU), in patients who have an inadequate response to H1-antihistamine treatment.

CSU is an unpredictable and severe disease of the skin, affecting 0.5-1% of the global population at any time. It is characterized by the development of itchy, painful wheals (hives), swelling (angioedema), or both, lasting for at least 6 weeks and occurring with no known cause3. CSU can be challenging or frustrating for patients due to the severity and unpredictable nature. It most commonly persists for 1-5 years, but in some cases even longer.

“Chronic spontaneous urticaria is a debilitating disease that may significantly impact a patient’s life. With so few treatment options available, patients are looking for more and better therapies to control their disease,” said Angelika Jahreis MD, PhD, Novartis Global Head Development Unit Immunology, Hepatology & Dermatology. “The US FDA Breakthrough Therapy designation recognizes the need for a more effective treatment for this unpredictable, systemic and debilitating disease.”

Ligelizumab (QGE031) is a next generation monoclonal anti-immunoglobulin E (IgE) antibody. Ligelizumab is thought to work by blocking the IgE/FceRI pathway, a key driver of the inflammatory process in CSU. In a phase IIb dose-finding trial, more patients experienced complete resolution of wheals (hives) with ligelizumab compared with Xolair (omalizumab). No safety concerns were found with ligelizumab compared with omalizumab or placebo in a phase IIb dose-finding trial in CSU patients with inadequate control on antihistamines.

Ligelizumab compared with omalizumab is currently being investigated in ongoing phase III clinical trial programs including PEARL 1 and PEARL 2. The clinical trials have recruited more than 2,000 patients globally across 48 countries and results are expected in the second half of 20219

Date: 23-Feb-2021

US FDA Grants Breakthrough Therapy Designation To Immunocores Tebentafusp To Treat Unresectable Or Metastatic Uveal Melanoma

Immunocore, a late-stage biotechnology company, announced that the US Food and Drug Administration (FDA) granted Breakthrough Therapy Designation (BTD) to tebentafusp (IMCgp100) for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM).

Bahija Jallal, chief executive officer of Immunocore, said: “We are delighted that the FDA has granted Breakthrough Therapy Designation for tebentafusp based on the survival benefit from our phase 3 clinical trial announced in November 2020. There is an urgent need for an approved treatment for this rare and aggressive form of melanoma and we look forward to continuing to work with regulators to bring tebentafusp to patients as quickly as possible.”

In an initial pre-planned interim analysis of a randomized phase 3 clinical trial (IMCgp100-202) in previously untreated metastatic uveal melanoma, a cancer that has historically proven to be insensitive to other immunotherapies, tebentafusp demonstrated superior overall survival (OS) benefit as a monotherapy. The primary endpoint was achieved when the OS Hazard Ratio (HR) in the intent-to-treat population favored tebentafusp, HR=0.51 (95% CI: 0.36, 0.71); p< 0.0001, over investigator’s choice (82% pembrolizumab; 12% ipilimumab; 6% dacarbazine).

The Breakthrough Therapy Designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).

Tebentafusp has also been granted Fast Track Designation and orphan drug designation from the FDA for uveal melanoma and Promising Innovative Medicine designation under the UK Early Access to Medicines Scheme. Immunocore will be working with the FDA to facilitate submission of a BLA for tebentafusp. If approved, Immunocore believes tebentafusp would be the first new therapy for the treatment of metastatic uveal melanoma in 40 years.


Tebentafusp is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. Tebentafusp specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma, and is the first molecule developed using Immunocore’s ImmTAC technology platform designed to redirect and activate T cells to recognise and kill tumour cells. Tebentafusp has been granted Breakthrough Therapy Designation, Fast Track designation and orphan drug designation by the FDA in the United States and Promising Innovative Medicine (PIM) designation under the UK Early Access to Medicines Scheme for metastatic uveal melanoma.

Uveal melanoma is a rare and aggressive form of melanoma, which affects the eye. Metastatic uveal melanoma typically has a poor prognosis and has no currently accepted optimal management or treatment. Although it is the most common primary intraocular malignancy in adults, the diagnosis is rare, with approximately 8,000 new patients diagnosed globally each year (1,600-2,000 cases per year in the United States). Up to 50% of people with uveal melanoma will eventually develop metastatic disease. When the cancer spreads beyond the eye, only approximately half of patients will survive for one year.

Immunocore is a late-stage biotechnology company pioneering the development of a novel class of TCR bispecific immunotherapies called ImmTAX – Immune mobilizing monoclonal TCRs Against X disease – designed to treat a broad range of diseases, including cancer, infectious and autoimmune.