FDA Approves Rozlytrek (entrectinib) for People With ROS1-Positive, Metastatic Non-Small Cell Lung Cancer and NTRK Gene Fusion-Positive Solid Tumors

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY),  announced  the U.S. Food and Drug Administration (FDA) has approval of  Rozlytrek (entrectinib) for the treatment of adults with ROS1-positive, metastatic non-small cell lung cancer (NSCLC). The FDA has also granted accelerated approval to Rozlytrek for the treatment of adult and pediatric patients 12 years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy.

These approvals are based on results from the integrated analysis of the pivotal Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials, and data from the Phase I/II STARTRK-NG study. In the integrated analysis, Rozlytrek was studied in several solid tumor types, including breast, cholangiocarcinoma, colorectal, gynecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers. In ROS1-positive, metastatic NSCLC, Rozlytrek shrank tumors in 78% of people with the disease (overall response rate [ORR]; N=51) and the duration of response (DoR) ranged from 1.8 to 36.8+ months (N=40 out of 51). Rozlytrek also shrank tumors in more than half of people with NTRK gene fusion-positive, locally advanced or metastatic solid tumors (ORR=57%; N=54), and objective responses were observed across 10 tumor types (DoR ranged from 2.8 to 26.0+ months; N=31 out of 54). Objective responses to Rozlytrek were seen in people with central nervous system (CNS) metastases at baseline.

“Rozlytrek’s FDA approval for two rare types of cancer is an important advance for patients, combining a targeted medicine and genomic testing to bring this new treatment option to patients who are waiting,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “Rozlytrek is the first FDA-approved treatment that selectively targets both ROS1 and NTRK fusions, and, importantly, has also shown responses in these rare cancer types that have spread to the brain.”

“The identification of actionable biomarkers like ROS1 has brought about significant progress in the treatment of lung cancer. This approval brings further hope to people with this rare type of the disease,” said Janet Freeman-Daily, co-founder of The ROS1ders, a group of patients and caregivers affected by ROS1-positive lung cancer. “Up to 40% of people with ROS1-positive non-small cell lung cancer have tumors that have spread to the brain, so now there is a new treatment option for those patients.”

The most common adverse reactions (≥20 percent) with Rozlytrek were fatigue, constipation, altered sense of taste (dysgeusia), swelling (edema), dizziness, diarrhea, nausea, nervous system disorders (dysesthesia), shortness of breath (dyspnea), muscle pain (myalgia), cognitive impairment, increased weight, cough, vomiting, fever (pyrexia), joint pain (arthralgia) and vision disorders.

The FDA’s Accelerated Approval Program allows conditional approval of a medicine that fills an unmet medical need for a serious or life-threatening disease or condition. The accelerated approval of Rozlytrek for NTRK gene fusion-positive solid tumors is based on tumor response rate and durability of response, and continued approval may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Biomarker testing for ROS1 in NSCLC and NTRK gene fusions across all solid tumors is the only way to identify people who are eligible for treatment with Rozlytrek. Genentech is leveraging its expertise in developing personalized medicines and advanced diagnostics, in conjunction with Foundation Medicine, to help identify people with ROS1 and NTRK gene fusions. Foundation Medicine will submit Foundation®One CDx to the FDA for approval as a companion diagnostic for Rozlytrek. An FDA-approved companion diagnostic for Rozlytrek is not available at this time.

Rozlytrek is now available in the United States for adults and children 12 years of age and older. For those who qualify, Genentech offers patient assistance programs for people prescribed Rozlytrek by their doctor through Genentech Access Solutions. Please contact Genentech Access Solutions at (866) 422-2377 or visit http://www.Genentech-Access.comfor more information.

About the Integrated Analysis

This approval is based on an integrated analysis including data from 51 people with ROS1-positive NSCLC and 54 people with locally advanced or metastatic NTRK gene fusion-positive solid tumors (10 tumor types, >19 histopathologies) from the Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials. This approval is also based on data from the Phase I/II STARTRK-NG study in pediatric patients. The studies enrolled people across 15 countries and more than 150 clinical trial sites. Safety was assessed from an integrated analysis of 355 people across these four trials.

https://en.wikipedia.org/wiki/Entrectinib

https://pubchem.ncbi.nlm.nih.gov/compound/Entrectinib#section=2D-Structure

FDA Approves EluRyng (etonogestrel/ethinyl estradiol vaginal ring), the First Generic NuvaRing

Amneal Pharmaceuticals, Inc. (NYSE: AMRX) (“Amneal” or the “Company”) announced that it has received Abbreviated New Drug Application (ANDA) approval from the U.S. Food and Drug Administration (FDA) for EluRyng™ (etonogestrel/Ethinyl estradiol vaginal ring), the first generic version of NuvaRing®. Amneal has initiated commercialization activities for EluRyng, which is being manufactured internally and launching today.

We are pleased to announce FDA approval of EluRyng, one of 15 new, complex products we expect to launch over the next 18 to 24 months,” said Chirag and Chintu Patel, Co-Chief Executive Officers. “This milestone underscores Amneal’s deep scientific and regulatory capabilities and our ability to overcome significant barriers to entry, including complex formulation development and specialized manufacturing requirements. In addition, EluRyng adds a differentiated, complex dosage form to our portfolio, and bringing this product to market reflects our commitment to improving affordable access to complex drug products. Looking ahead, we remain enthusiastic about the additional high-value opportunities in our pipeline that are designed to improve the lives of patients and drive meaningful growth and value-creation for our shareholders and other stakeholders in 2020 and beyond.”

According to IQVIA™, a leading healthcare data and analytics provider, NuvaRing U.S. annual sales for the 12 months ended October 31, 2019 were approximately $976 million.
About Amneal

Amneal Pharmaceuticals, Inc. (NYSE: AMRX), headquartered in Bridgewater, NJ, is a fully-integrated pharmaceutical company focused on the development, manufacture and distribution of generic and specialty drug products. The Company has manufacturing operations in North America, Asia, and Europe, working together to bring high-quality medicines to patients primarily within the United States.

Amneal has an extensive portfolio of more than 300 generic medicines and is expanding its portfolio to include complex dosage forms, including biosimilars, in a broad range of therapeutic areas. The Company also markets a portfolio of branded pharmaceutical products through its Specialty segment focused principally on the central nervous system and endocrine disorders. For more information, visit www.amneal.com.

https://www.webmd.com/drugs/2/drug-63403/etonogestrel-ethinyl-estradiol-vaginal/details

FDA Approves Nourianz (istradefylline) as an Add-On Drug to Treat Off Episodes in Adults with Parkinson’s Disease

Kyowa Kirin Co., Ltd., (Kyowa Kirin, TYO: 4151) announced the U.S. Food and Drug Administration (FDA) has granted approval for Nourianz (istradefylline) for use as adjunctive treatment to levodopa/carbidopa in adult patients with Parkinson’s disease (PD) experiencing “OFF” episodes.

“We are proud that Nourianz is now ready to help adult patients with Parkinson’s disease in the US,” said Tomohiro Sudo, Head of Global Product Management Office of Kyowa Kirin. “We believe that Nourianz could be an important contributor to improve treatment outcomes. We will keep working to bring the product to patients globally.”

“Kyowa Kirin has a commitment to global health and well-being by creating new value through the pursuit of advances in life sciences and technology particularly in oncology, nephrology, immunology, and the central nervous system,” said Tom Stratford, President of Kyowa Kirin USA Holdings, Inc. “Today's FDA approval of Nourianz is an important milestone and provides US patients with a novel non-dopaminergic once-a-day oral treatment option to be used in conjunction with levodopa/carbidopa for Parkinson’s disease.”

“Today’s approval is the culmination of decades of perseverance in exploring the science and clinical effects of istradefylline and inhibition of adenosine A2A receptor signaling in people with Parkinson’s disease,” said Jeffrey S. Humphrey, MD, Chief Development Officer of Kyowa Kirin Pharmaceutical Development, Inc. “In clinical studies, istradefylline, used as adjunctive treatment to levodopa/carbidopa in adult patients with PD experiencing 'OFF' episodes, was associated with a decrease in OFF Time and increase in ON Time without troublesome dyskinesia. We are grateful for the FDA approval and for the many dedicated scientists and patients whose participation in our research programs has resulted in a new treatment option for Parkinson's disease.”

“Istradefylline is an Adenosine A2A receptor antagonist, and is a novel non-dopaminergic pharmacologic approach to treating OFF episodes for people living with PD,” said Dr. Stuart Isaacson, MD, Parkinson’s Disease and Movement Disorders Center of Boca Raton, Florida. “Based on data from four clinical studies, istradefylline taken as an adjunct to levodopa significantly improved OFF time and demonstrated a well-tolerated safety profile. Istradefylline represents an important new treatment option for patients with Parkinson's disease who experience 'OFF' episodes.”

The FDA approval of Nourianz is based on findings from randomized, multi-center, double-blind, placebo-controlled trials in patients with PD taking a stable dose of levodopa/carbidopa with or without other PD medications.

The Kyowa Kirin Group companies strive to contribute to the health and well-being of people around the world by creating new value through the pursuit of advances in life sciences and technologies.

Please see Nourianz indication and Important Safety Information below.

Indication

Nourianz (istradefylline) is an adenosine receptor antagonist indicated as adjunctive treatment to levodopa/carbidopa in adult patients with Parkinson’s disease (PD) experiencing “off” episodes.

Important Safety Information

Warnings and Precautions

Dyskinesia: Nourianz in combination with levodopa may cause dyskinesia or exacerbate pre-existing dyskinesia. In clinical trials, 1% of patients treated with either Nourianz 20 mg or 40 mg discontinued treatment because of dyskinesia, compared to 0% for placebo.

FDA Approves Katerzia (amlodipine) Oral Suspension for Pediatric Patients 6 Years of Age and Older

In continuation of my update on amlodipine

Azurity Pharmaceuticals, a specialty pharmaceutical company that makes safe, high-quality treatments for patients requiring customized formulations for their care, announced  that the U.S. Food and Drug Administration (FDA) has approved Katerzia (amlodipine) Oral Suspension, 1 mg/mL, the first and only FDA-approved amlodipine oral suspension. Katerzia is indicated for the treatment of hypertension (high blood pressure) in adults and pediatric patients 6 years of age and older and coronary artery disease in adults.

“We are pleased to announce the FDA approval of Katerzia”, said Neal Muni, MD, MSPH, President and Chief Executive Officer of Azurity Pharmaceuticals. “The addition of Katerzia complements our existing pediatric hypertension portfolio and will strengthen the overall offering from Azurity. It is also our first product approval since CutisPharma and Silvergate Pharmaceuticals came together to make Azurity Pharmaceuticals, making this a truly exciting time.”

Katerzia offers a ready-to-use (simply shake) oral suspension for children 6 years of age and older that require or prefer an oral liquid option of amlodipine. Appropriate dosing for children is now simple, safe, and effective, while providing the assurance of quality as an FDA-approved product. Katerzia will be readily available through an extensive network of pharmacies and a qualified mail order service. For additional information on Katerzia, please email media@azurity.com.

https://en.wikipedia.org/wiki/Amlodipine

Turalio (Pexidartinib) Approved to Treat Tenosynovial Giant Cell Tumor

In continuation of my update on pexidartinib 

Turalio (pexidartinib) capsules have been approved to treat adults with symptomatic tenosynovial giant cell tumor (TGCT), the U.S. Food and Drug Administration announced.

The drug was approved for patients with TGCT with severe morbidity or functional limitations that has not improved with surgery. Turalio is only available through the Risk Evaluation and Mitigation Strategy Program.

Approval was based on data from a multicenter international clinical trial of 120 patients. After 25 weeks, patients who received Turalio had a statistically significant improvement in overall response rate (ORR) to an ORR of 38 percent versus no response in patients who received placebo. Fifteen percent of patients had a complete response and 23 percent had a partial response. Among patients followed for a minimum of six months following initial response, 22 of 23 patients maintained their response for six months or longer; all 13 patients who initially responded and were followed for a minimum of 12 months maintained their response for 12 months or longer.

Commonly reported side effects include lactate dehydrogenase, increased aspartate aminotransferase, loss of hair color, increased alanine aminotransferase, and increased cholesterol. Side effects also include neutropenia, increased alkaline phosphatase, decreased lymphocytes, eye edema, decreased hemoglobin, rash, dysgeusia, and decreased phosphate. A Boxed Warning on the prescription information for Turalio warns about the risk for serious and potentially fatal liver injury and advises health care professionals to monitor patients' liver tests before and during treatment and to alter or discontinue use of the drug if liver tests are abnormal.

https://en.wikipedia.org/wiki/Pexidartinib

FDA Approves Gadavist (gadobutrol) Contrast Agent for Use in Cardiac MR in Adult Patients with Known or Suspected Coronary Artery Disease

In continuation of my update on Gadavist (gadobutrol)

Bayer announced today the U.S. Food and Drug Administration (FDA) has approved Gadavist (gadobutrol) injection for use in cardiac magnetic resonance (MR) imaging to assess myocardial perfusion (stress, rest) and late gadolinium enhancement in adult patients with known or suspected coronary artery disease (CAD). Gadavist is now the first and only contrast agent FDA approved for use in cardiac MR – an important diagnostic tool for patients with CAD.

"Gadobutrol-enhanced cardiac MR demonstrated efficacy in a large global multicenter clinical trial," said Daniel S. Berman, MD, FACC, Chief of Cardiac Imaging and Nuclear Cardiology at the Cedars-Sinai Heart Institute and the S. Mark Taper Foundation Imaging Center. "The FDA approval is a landmark for making this validated, non-invasive method available to healthcare professionals to evaluate their patients for the most common form of heart disease in the world."

The approval was based on two multinational, non-randomized, blinded-read Phase 3 studies of almost 1,000 adults with suspected or known CAD based on signs and symptoms. Nearly 800 of those patients were evaluated for efficacy. First approved in 2011, cardiac MR is now the fourth FDA approved indication for Gadavist.2

The Society for Cardiovascular Magnetic Resonance recognizes cardiac MR as a non-invasive tool that provides relevant and actionable information to healthcare professionals.3

"We now have an approved contrast agent for use in cardiac MR to assess perfusion and late gadolinium enhancement in less than one hour," said Scott Flamm, MD, MBA, Head of Cardiovascular Imaging, Cleveland Clinic. "A Gadavist-enhanced cardiac MR is a key diagnostic tool, providing additional important clinical information, which can help physicians manage their patients with known or suspected CAD."

A disease that affects approximately 16.5 million Americans, CAD develops when the major blood vessels that supply the heart with blood, oxygen and nutrients (coronary arteries) become damaged or diseased.1,5 Cholesterol-containing deposits (plaque) in the arteries and inflammation are usually the cause of CAD. When plaque builds up, it narrows the coronary arteries, decreasing blood flow to the heart. Eventually, the decreased blood flow may cause chest pain (angina), shortness of breath, or other coronary artery disease signs and symptoms. A complete blockage can cause a heart attack.4

"This latest FDA approval represents another first from Bayer, as Gadavist is the first and only contrast agent approved for cardiac MR," said Dennis Durmis, SVP and Head of Americas Region at Bayer Radiology. "Not only does this approval add to our existing indications for Gadavist, expanding scientific knowledge, but also underscores our dedication to research and provides radiologists and cardiologists with another diagnostic option as they manage their patients with known or suspected CAD."

About Gadavist

Gadavist (gadobutrol) injection was first approved in the U.S. in 2011 for intravenous use in magnetic resonance (MR) imaging in adults and children (2 years of age and older) to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system. Gadavist was further approved in the U.S. in 2014 for MR of the breast in adult patients to assess the presence and extent of malignant breast disease and for pediatric patients less than 2 years of age, including term neonates, to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system. In 2016, it was approved in the U.S. for use with magnetic resonance angiography (MRA) to evaluate known or suspected supra-aortic or renal artery disease in adult and pediatric patients including term neonates.

Gadavist, also known as Gadovist® and Gadovist® 1.0 in other regions, is the U.S. brand name of the aqueous 1.0M solution of gadobutrol, a gadolinium (Gd)-based extracellular contrast agent for MRI with a macrocyclic structure. The safety profile of Gadavist has been established in clinical trials involving 7,713 patients (including 184 pediatric patients ages 0-17). The safety and effectiveness of Gadavist have not been established in preterm neonates for any indication or in pediatric patients of any age for use with MR to assess the presence and extent of malignant breast disease, or for use in cardiac MR to assess myocardial perfusion (stress, rest) and late gadolinium enhancement in patients with known or suspected coronary artery disease (CAD). Please see Important Safety Information, including Boxed Warning below.

https://en.wikipedia.org/wiki/Gadobutrol

FDA Approves Nouress (cysteine hydrochloride) Injection for Treating Neonate Patients Requiring Total Parenteral Nutrition (TPN)

Avadel Pharmaceuticals plc (Nasdaq: AVDL) announced today that the U.S. Food and Drug Administration (FDA) has approved Nouress (AV001), a cysteine hydrochloride injection, a critical drug for treating neonatal patients requiring total parenteral nutrition (TPN).

In addition, Avadel announced today that the United States Patent and Trademark Office (USPTO) recently issued United States Patent No. 10,493,051 covering cysteine solutions, including the approved Nouress product. This patent is listed in the Orange Book for Nouress and is set to expire in March of 2039. Avadel has additional U.S. patent applications pending for Nouress.

“We are pleased to receive FDA approval for Nouress, which validates our strategy of developing innovative medicines for patients,” said Greg Divis, Chief Executive Officer of Avadel. “Nouress is the fourth FDA approved product in our sterile injectable hospital business. The cash flow generated by this legacy business is supporting the clinical development costs from our lead program, FT218, which is currently expected to announce topline data from the pivotal Phase 3 REST-ON trial in the second quarter of 2020. We believe that as a once-nightly formulated sodium oxybate, FT218, if approved by the FDA, has the potential to take a significant share of the twice-nightly sodium oxybate market, which is currently valued at an estimated annualized rate of $1.7 billion.”

Avadel is currently evaluating the timing and process for a commercial launch of Nouress in the United States. In this regard, a competitor received FDA approval earlier this year for its cysteine hydrochloride injection and more recently was granted a U.S. patent, which Avadel is assessing along with other market factors. 

Due to a historical lack of reliable supply, U.S. markets previously imported cysteine hydrochloride injection from Canada under special FDA rules allowing shortage drugs to be sourced abroad if no domestic supplies are available. With FDA approvals of Nouress and another U.S. company’s cysteine hydrochloride injection earlier this year, Avadel expects domestic supply of cysteine hydrochloride injection will be sufficient to support the entire U.S. market, which, under FDA regulations, should preclude further import or U.S. marketing of unapproved cysteine hydrochloride injection products.  Under these potential market conditions, the U.S. annual market for cysteine hydrochloride could be greater than $50 million. 

https://pubchem.ncbi.nlm.nih.gov/compound/L-Cysteine-hydrochloride

https://en.wikipedia.org/wiki/Cysteine

https://www.drugbank.ca/salts/DBSALT001754









FDA Approves Nouress (cysteine hydrochloride) Injection for Treating Neonate Patients Requiring Total Parenteral Nutrition (TPN)

FDA Approves Otezla (apremilast) for the Treatment of Oral Ulcers Associated with Behçet’s Disease

In continuation of my update on Otezla (apremilast) 

Celgene Corporation today announced that the U.S. Food and Drug Administration (FDA) has approved Otezla (apremilast) 30 mg twice daily (BID) for the treatment of adult patients with oral ulcers associated with Behçet’s Disease. Otezla, an oral, selective inhibitor of phosphodiesterase 4 (PDE4), is the first and only approved treatment option for oral ulcers associated with Behçet’s Disease, a rare, chronic, multisystem inflammatory disease that is difficult to treat.

“Oral ulcers are a recurring and debilitating manifestation that affects nearlyeveryone living with Behçet’s Disease,and have an important negative impact on the quality of life for these patients,” said Yusuf Yazici, M.D., Clinical Associate Professor, Department of Medicine, New York University Langone Health. “In the clinical trial, Otezla demonstrated improvements in measures of oral ulcers at week 12. Otezla has the potential to be a needed treatment option for U.S. patients and their physicians, who previously had limited options available.”

Behçet’s Disease, also known as Behçet’s Syndrome, affects approximately 5 in 100,000 people in the U.S. Oral ulcers, the most common manifestation of Behçet’s Disease occurring in more than 98% of patients, can be painful, disabling and negatively affect quality of life.3

“We are excited to provide the first and only FDA-approved treatment for oral ulcers associated with Behçet’s Disease,” said Terrie Curran, President, Celgene Inflammation & Immunology. “This approval is a reflection of Celgene’s commitment to research in areas of high unmet need, including rare diseases such as Behçet’s Disease. We remain dedicated to further studying Otezla and its role in inflammatory conditions.”

The FDA approval was based on efficacy and safety results from the randomized, placebo-controlled, double-blind Phase 3 RELIEF™ study evaluating Otezla in 207 adult patients with Behçet’s Disease with active oral ulcers who were previously treated with at least one nonbiologic medication and were candidates for systemic therapy. Results showed Otezla 30 mg BID resulted in a 42.7 point reduction from baseline in the pain of oral ulcers as measured by the visual analog scale (VAS) at week 12, compared with an 18.7 point reduction with placebo. The proportion of patients achieving an oral ulcer complete response (oral ulcer-free) at week 12 was 52.9% in the Otezla arm and 22.3% in the placebo arm. The proportion of patients achieving oral ulcer complete response by week 6 and who remained oral ulcer-free for at least six additional weeks during the 12-week treatment phase was 29.8% in the Otezla arm and 4.9% in the placebo arm. The daily average number of oral ulcers during the 12-week treatment phase was 1.5 in the Otezla arm and 2.6 in the placebo arm (based on oral ulcer counts measured at baseline and at weeks 1, 2, 4, 6, 8, 10 and 12).

“Behçet’s Disease is a chronic inflammatory disease in which patients present with symptoms such as oral ulcers that can have a significant impact on daily life,” said Mirta Avila Santos, M.D., Executive Director, American Behçet’s Disease Association. “Today’s approval for Otezla marks an important milestone for people with Behçet’s Disease who have been eagerly waiting for treatment options for their oral ulcers.”

The most common adverse events observed occurring in ≥10% of patients in the RELIEF trial were diarrhea (41.3% with Otezla; 20.4% for placebo), nausea (19.2% with Otezla; 10.7% for placebo), headache (14.4% with Otezla; 10.7% for placebo) and upper respiratory tract infection (11.5% with Otezla; 4.9% for placebo). The safety profile was consistent with the known safety profile of Otezla.

Otezla is now approved for three indications in the U.S., including the treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, adult patients with active psoriatic arthritis and adult patients with oral ulcers associated with Behçet’s Disease. Since its initial FDA approval in 2014, Otezla has been prescribed to more than 250,000 patients with moderate to severe plaque psoriasis or active psoriatic arthritis in the U.S.

Otezla is available in the U.S. and is dispensed through a comprehensive network of specialty pharmacies. For more information about accessing Otezla and patient support services (including reimbursement assistance and 24/7 nurse support), doctors and patients can contact Otezla® SupportPlus™ at 1-844-4OTEZLA (1-844-468-3952) or visit www.OTEZLA.com for more information.

Celgene anticipates a regulatory decision for Otezla in oral ulcers associated with Behçet’s Disease from the Pharmaceuticals and Medical Devices Agency in Japan in the second half of 2019. The Company also submitted a Type II Variation to the Marketing Authorization Application earlier this year seeking approval in the European Union.

https://en.wikipedia.org/wiki/Apremilast

FDA Approves Accrufer (ferric maltol) for the Treatment of Iron Deficiency in Adults

Shield Therapeutics plc (LSE: STX), a commercial stage, pharmaceutical company with a focus on addressing iron deficiency, announces that the U.S. Food and Drug Administration (FDA) has approved its lead product Accrufer® (Feraccru® in the European Union and Switzerland) for the treatment of iron deficiency in adults.

With this broad label approval Accrufer (as the product will be marketed in the USA) has taken a big step towards exploiting the very large commercial opportunity in the USA, the world’s largest and most attractively reimbursed pharmaceutical market. Market research suggests that the prescription market for iron replacement therapy in the USA is worth over $1.0bn annually. There are between 8 million and 9 million patients in the USA who suffer from iron deficiency anaemia and management estimate potentially two to three times this number require treatment for iron deficiency.

Accrufer’s confirmed efficacy, together with its good tolerability and mode of absorption - by which the body absorbs only as much iron from Accrufer as it needs - means that the product could be the ideal choice for iron deficient patients who cannot tolerate salt-based oral iron alternatives. These features, combined with the noninferiority results from the AEGIS-H2H study announced in March 2019, mean that treatment with Accrufer might remove the need for patients to progress to intravenous iron therapy, leading to a change in the current paradigm for the treatment of iron deficiency anaemia.

Together with its advisors, Shield is in discussions with a number of potential commercial partners for the US opportunity for Accrufer and looks forward to providing updates on these discussions in due course. Feraccru is already approved in both the European Union and Switzerland for the treatment of iron deficiency in adults and commercialisation activities in these territories are progressing well via Shield’s licensing partners.

Carl Sterritt, CEO of Shield Therapeutics: “We are delighted that the FDA has approved the new drug application for our lead asset. This is a further major milestone for the Company which we have worked tirelessly to achieve, and I am very proud to lead the team within Shield that has made this happen. With this broad approval and IP protection out to 2035, Feraccru®/ Accrufer® has a real and very attractive long-term market opportunity to exploit in the USA. We have been pleased with the levels of interest and engagement shown by 3rd parties in commercialising Accrufer® in the USA and we look forward to finalising these discussions and appointing a commercial partner In the world’s most attractive pharmaceutical market,so that more patients with iron deficiency can benefit from treatment with Accrufer® at the earliest opportunity.”

Jackie Mitchell, VP Regulatory Affairs of Shield Therapeutics: “The broad label that the FDA has granted provides a very strong signal as to the tolerability and efficacy profile of Feraccru®/ Accrufer® and provides a novel and convenient treatment alternative to the millions of US patients who routinely suffer with iron deficiency. We believe that this broad approval, together with the recent clinical trial data on Feraccru® that showed it to be non-inferior in treatment effect to Ferinject®/ Injectafer®, the leading IV iron therapy, can lead to a change in the current paradigm for the treatment iron deficiency anaemia

https://pubchem.ncbi.nlm.nih.gov/compound/Ferric-maltol#section=2D-Structure

FDA Approves Nubeqa (darolutamide) for Men with Non-Metastatic Castration-Resistant Prostate Cancer

The U.S. Food and Drug Administration (FDA) today approved Nubeqa (darolutamide), an androgen receptor inhibitor (ARi), for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC). The FDA approval is based on the Phase III ARAMIS trial evaluating Nubeqa plus androgen deprivation therapy (ADT), which demonstrated a highly significant improvement in the primary efficacy endpoint of metastasis-free survival (MFS), with a median of 40.4 months versus 18.4 months for placebo plus ADT (p<0.0001).1 MFS is defined as the time from randomization to the time of first evidence of blinded independent central review (BICR)-confirmed distant metastasis or death from any cause within 33 weeks after the last evaluable scan, whichever occurred first. Nubeqa was approved under the FDA's Priority Review designation, which is reserved for medicines that may provide significant improvements in the safety or effectiveness of the treatment for serious conditions.

"Patients at this stage of prostate cancer typically don't have symptoms of the disease. The overarching goals of treatment in this setting are to delay the spread of prostate cancer and limit the burdensome side effects of therapy," said Matthew Smith, M.D., Ph.D., Director of the Genitourinary Malignancies Program, Massachusetts General Hospital Cancer Center. "This approval marks an important new option for the prostate cancer community."

In the U.S., over 73,000 men are estimated to be diagnosed with castration-resistant prostate cancer (CRPC) in 2019. About 40 percent of these patients have prostate cancer that has not spread to other parts of the body and is also associated with a rising prostate-specific antigen (PSA) level, despite a castrate testosterone level, which is known as nmCRPC. This is important because about one-third of men with nmCRPC go on to develop metastases within two years.4 PSA monitoring is important to identify patients and help offset undertreatment in men before the disease spreads.

"We know that men with nmCRPC are still in the prime of their lives and are at a critical point in their disease when action needs to be taken," said Howard R. Soule, Ph.D., Executive Vice President and Chief Science Officer, Prostate Cancer Foundation (PCF). "For 26 years, PCF has been focused on research aimed at improving patient outcomes and we welcome the addition of new treatment options that provide men with more choices when working with their doctor to select what's right for them."

"With the approval of Nubeqa, we now have a new therapy that extends MFS and allows physicians greater flexibility to treat men living with nmCRPC," said Robert LaCaze, Member of the Executive Committee of Bayer's Pharmaceuticals Division and Head of the Oncology Strategic Business Unit at Bayer. "Bayer is proud to take this latest step forward in the nmCRPC treatment landscape. Nubeqa is the newest addition to our prostate cancer portfolio and reflects Bayer's commitment to finding treatments for men at different stages along the prostate cancer continuum."

In the ARAMIS trial, both arms showed a 9 percent discontinuation rate due to adverse reactions. The most frequent adverse reactions requiring discontinuation in patients who received Nubeqa included cardiac failure (0.4 percent), and death (0.4 percent).  Adverse reactions occurring more frequently in the Nubeqa arm (≥2 percent over placebo) were fatigue (16 percent versus 11 percent), pain in extremity (6 percent versus 3 percent) and rash (3 percent versus 1 percent). Nubeqa was not studied in women and there is a warning and precaution for embryo-fetal toxicity.

Overall survival (OS) and time to pain progression were additional secondary efficacy endpoints. OS data were not yet mature at the time of final MFS analysis.1 The MFS result was supported by a delay in time to pain progression, defined as at least a 2-point worsening from baseline of the pain score on Brief Pain Inventory-Short Form or initiation of opioids, in patients treated with Nubeqa as compared to placebo.1 Pain progression was reported in 28 percent of all patients on study.

Bayer has filed for approval of Nubeqa in the European Union (EU), Japan, and with other health authorities. Nubeqa is developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company.