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.

FDA Approves AirDuo Digihaler (fluticasone propionate and salmeterol) Inhalation Powder for Asthma

In continuation of my update on (fluticasone propionate and salmeterol

   

Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) announced today that the U.S. Food and Drug Administration (FDA) has approved AirDuo® Digihaler™ (fluticasone propionate 113 mcg and salmeterol 14 mcg) Inhalation Powder, a combination therapy digital inhaler with built-in sensors that connects to a companion mobile application to provide information on inhaler use to people with asthma. AirDuo Digihaler is indicated for the treatment of asthma in patients aged 12 years and older. AirDuo Digihaler is not used to relieve sudden breathing problems and won’t replace a rescue inhaler.

“We are thrilled to be able to expand our Digihaler™ portfolio to now include a maintenance treatment,” said Tushar Shah, M.D., Global Head of Specialty Clinical Development at Teva Pharmaceuticals. “With this approval, patients can now track how frequently they are using their inhalers. Granting patients the ability to track their maintenance inhaler use may help inform conversations with their doctors about treatment adherence and proper technique.”

Like ProAir® Digihaler™ (albuterol sulfate 117 mcg) inhalation powder, indicated for the treatment or prevention of bronchospasm in patients aged four years and older with reversible obstructive airway disease, and for prevention of exercise-induced bronchospasm (EIB) in patients four years and older, AirDuo® Digihaler™ contains built-in sensors that detect when the inhaler is used and measure inspiratory flow rates. This data is then sent to a companion mobile app using Bluetooth® Wireless Technology so that patients can review their data over time, and if desired, share it with their healthcare providers. Patients can also schedule reminders on their smartphone to take their AirDuo® Digihaler™ as prescribed.

“Even the most diligent asthma patients may not realize they are not following their treatment regimen, despite their best efforts,” said Dr. Nabeel Farooqui, MD, FAAAAI, FACAAI, Assistant Professor, Department of Medicine, Indiana University School of Medicine. “The ability to now measure their inspiratory flow rates and track their maintenance medication use, as well as the frequency with which they use their inhaler, may provide important data and insights to help inform treatment discussions with physicians. As a doctor, it’s exciting that my patients are able to share this type of information with me.”

The approval of AirDuo Digihaler is based on the review of the supplemental new drug application (sNDA) submitted by Teva to the FDA. AirDuo Digihaler combines a breath-actuated, multi-dose dry powder inhaler with fluticasone propionate, an inhaled corticosteroid (ICS) medicine that may help to decrease inflammation in the lungs, which can lead to breathing problems, and salmeterol, a long acting beta2 adrenergic agonist (LABA), which helps the muscles around the airways in the lungs stay relaxed in order to prevent symptoms. AirDuo Digihaler contains salmeterol. LABA medicines such as salmeterol when used alone increase the risk of hospitalizations and death from asthma problems. AirDuo Digihaler contains an ICS and a LABA. When an ICS and a LABA are used together, there is not a significant increased risk in hospitalizations and death from asthma problems.

AirDuo Digihaler was approved in a low, medium and high dose: 55/14 mcg, 113/14 mcg and 232/14 mcg administered as one inhalation twice daily. As a fixed dose combination asthma therapy containing an ICS and a LABA, AirDuo Digihaler contains the same active ingredients as Advair Diskus, which is also approved in low, medium and high doses: 100/50 mcg, 250/50 mcg and 500/50 mcg.

“For the 25 million Americans living with asthma1, advancements like this one are important and could help patients track their inhaler use and frequency,” said Tonya Winders, President & CEO of the Allergy & Asthma Network. “Allowing patients access to both their rescue and maintenance inhaler use information on their smartphones is a promising step towards potentially fostering greater discussions about asthma management.”

“The approval of AirDuo Digihaler is an important step for Teva and the respiratory community to create a technology platform for use in asthma management along with the previously-approved ProAir Digihaler,” said Sven Dethlefs, Executive Vice President, Global Marketing & Portfolio. “This technology aims at delivering innovations through cloud-based services with the target to provide new insights to guide treatment choices for caregivers to help them improve outcomes for asthma patients.”

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

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

Selinexor Offers Hope Against a Tough-to-Treat Blood Cancer

In continuation of my update on Selinexor

Patients with a form of blood cancer known as multiple myeloma who haven't responded to other therapies might have a new weapon against the disease, researchers say.

A drug called selinexor appeared to help patients with the blood and bone marrow cancer, according to a clinical trial involving 122 people.

"This study proved that a novel, first-in-class drug with a new mechanism of action can kill a patient's cancer cells," said study senior author Dr. Sundar Jagannath. He directs the multiple myeloma program at the Tisch Cancer Institute at Mount Sinai in New York City.

Selinexor also "worked in patients who had exhausted every other treatment and who would have been placed on hospice care otherwise," Jagannath said in a hospital news release.

In the trial, which was funded by the drug's maker, Karyopharm, patients at centers in the United States and Europe received a combination therapy of two pills, selinexor and the standard anti-cancer medicine dexamethasone.

As reported in the Aug. 22 issue of the New England Journal of Medicine, nearly 40% of the patients showed at least a minimal response to the therapy within one or two months. There were "significant" responses in more than a quarter of the patients, the researchers said, and two patients had their cancers go into complete remission.

As the team explained, selinexor works in a new way to fight myeloma, blocking a key mechanism in cancer cell growth and causing the cell to die.

Although the drug caused no toxicity to organs, there were side effects for some patients. These included low blood counts without bleeding, nausea, vomiting, lack of appetite or fatigue.

The U.S. Food and Drug Administration had already approved selinexor in early July to treat patients with multiple myeloma resistant to multiple therapies.

"This study is meaningful for patients with multiple myeloma who haven't had success on multiple other therapies," said study first author Dr. Ajai Chari, director of clinical research in the multiple myeloma program at the Tisch Cancer Institute.

"An increasing number of patients have resistance to the standard drugs used in the treatment of multiple myeloma, and the overall survival in these patients is short, sometimes less than three months," Chari said in the news release.

One myeloma expert unconnected to the research was heartened by the findings.

The trial results are "cautiously positive and very encouraging," said hematologist Dr. Kanti Rai. He works in the CLL Research and Treatment Program at Northwell Health Cancer Institute in New Hyde Park, N.Y.

Rai noted that while newer drugs are helping many multiple myeloma patients, others are still left without viable treatment options.

"The need for better treatments is especially urgent for those patients who are elderly, have compromised functions of other vital organs, have had multiple chemotherapy regimens in the past and still have evidence of progressive disease," he explained. "For such patients, unfortunately, death seems imminent."

Rai called the advent of selinexor "a positive step forward for patients with myeloma who otherwise have no hope for the future."

For their part, the Tisch researchers said they are also assessing selinexor for treatment of multiple myeloma in combination with other approved multiple myeloma drugs, as well for treatment of other cancers such lymphoma and ovarian cancer.

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

FDA Approves Turalio (pexidartinib) for the Treatment of Symptomatic Tenosynovial Giant Cell Tumors (TGCT) in Adults

U.S. Food and Drug Administration granted approval to Turalio (pexidartinib) capsules for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not responsive to improvement with surgery.

“TGCT can cause debilitating symptoms for patients such as pain, stiffness and limitation of movement. The tumor can significantly affect a patient’s quality of life and cause severe disability,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Surgery is the primary treatment option, but some patients are not eligible for surgery, and tumors can recur, even after the procedure. Today’s approval is the first FDA-approved therapy to treat this rare disease.”

TGCT is a rare tumor that affects the synovium (thin layer of tissue that covers the surfaces of the joint spaces) and tendon sheaths (layer of membrane that covers tendons, which are fibrous tissue that connect muscle to bone). The tumor is rarely malignant but causes the synovium and tendon sheaths to thicken and overgrow, causing damage to surrounding tissue.

The approval of Turalio was based on the results of a multi-center international clinical trial of 120 patients, 59 of whom received placebo. The primary efficacy endpoint was the overall response rate (ORR) analyzed after 25 weeks of treatment. The clinical trial demonstrated a statistically significant improvement in ORR in patients who received Turalio, with an ORR of 38%, compared to no responses in patients who received placebo. The complete response rate was 15% and the partial response rate was 23%. A total of 22 out of 23 responders who had been followed for a minimum of six months following the initial response maintained their response for six or more months, and a total of 13 out of 13 responders who had been followed for a minimum of 12 months following the initial response maintained their response for 12 or more months.

The prescribing information for Turalio includes a Boxed Warning to advise health care professionals and patients about the risk of serious and potentially fatal liver injury. Health care professionals should monitor liver tests prior to beginning treatment and at specified intervals during treatment. If liver tests become abnormal, Turalio may need to be withheld, the dose reduced, or permanently discontinued, depending on the severity of the liver injury. Turalio is available only through the Turalio Risk Evaluation and Mitigation Strategy (REMS) Program.

Common side effects for patients taking Turalio were increased lactate dehydrogenase (proteins that helps produce energy in the body), increased aspartate aminotransferase (enzymes that are mostly in the liver but also in muscles), loss of hair color, increased alanine aminotransferase (enzymes that are primarily in the liver and kidney) and increased cholesterol. Additional side effects included neutropenia (low level of white blood cells that help the immune system defend against disease and infection), increased alkaline phosphatase (enzymes that are mostly in the cells of bone and the liver), decreased lymphocytes (white blood cells that help the immune system defend against disease and infection), eye edema (swelling around the eyes), decreased hemoglobin (protein in red blood cells that carry oxygen), rash, dysgeusia (altered sense of taste) and decreased phosphate (electrolytes that help with energy).

The FDA advises health care professionals to tell females of reproductive age and males with a female partner of reproductive potential to use effective contraception during treatment with Turalio. Women who are pregnant or breastfeeding should not take Turalio because it may cause harm to a developing fetus or newborn baby. Turalio must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks.

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

FDA Approves Xpovio (selinexor) for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma

In continuation of my update on Selinexor

Karyopharm Therapeutics Inc. an oncology-focused pharmaceutical company, announced that the U.S. Food and Drug Administration (FDA) has approved oral Xpovio (selinexor), a nuclear export inhibitor, in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. The ongoing, randomized Phase 3 BOSTON study evaluating selinexor in combination with Velcade® (bortezomib) and low-dose dexamethasone will serve as the confirmatory trial. The FDA’s Accelerated Approval Program was developed to allow for expedited approval of drugs that treat serious conditions and that fill an unmet medical need.  

Karyopharm expects Xpovio to become commercially available in the U.S. on or before July 10, 2019.  A Marketing Authorization Application for selinexor is also currently under review by the European Medicines Agency.

“With today’s accelerated approval of Xpovio by the FDA, patients with heavily pretreated multiple myeloma will now have a new therapeutic option to treat their disease,” said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. “Discovering, developing and securing FDA approval for XPOVIO with its novel mechanism of action over the past decade required the dedication of many people, including the patients, caregivers and physicians involved in our clinical trials, along with the many employees at Karyopharm.  We are tremendously grateful for everyone’s contributions to this important milestone, and we look forward to the next stage in our pursuit of improving the lives of patients with cancer.”

“The 25.3% response rate seen in the subgroup of 83 patients in the pivotal Phase 2b STORM study that served as the basis for Xpovio's accelerated approval is clinically meaningful and a validated surrogate marker for clinical benefit in our patients with advanced refractory disease,” said Sundar Jagannath, MD, Director of the Multiple Myeloma Program, Professor of Medicine (Hematology and Medical Oncology) at Tisch Cancer Institute at Mount Sinai School of Medicine, and principal investigator of the STORM study.

“Despite recent advances in the treatment of multiple myeloma, almost all our patients will develop disease that is resistant to the five most commonly used anti-myeloma drugs we currently have available, and the prognosis for this patient population is particularly poor.  The accelerated approval of oral Xpovio marks an important advance in the treatment paradigm for patients with relapsed refractory multiple myeloma, and in my view, is an important addition to our therapeutic armamentarium,” said Dr. Paul Richardson, MD, Clinical Program Leader and Director of Clinical Research, Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute.

Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm, commented, “Having worked on novel drugs in myeloma beginning with Velcade in the year 2000, I have been thrilled to see such exciting progress overall in the field where there are substantial increases in patients’ duration and quality of life.  The accelerated approval of oral Xpovio targeting XPO1 represents the first approval against a new target in myeloma since 2015, and we look forward to advancing the further clinical development of Xpovio.”

https://pubchem.ncbi.nlm.nih.gov/compound/Selinexor

FDA Approves Thiola EC (tiopronin) for the Treatment of Cystinuria

Retrophin, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved 100 mg and 300 mg tablets of Thiola EC (tiopronin), a new enteric-coated formulation of Thiola (tiopronin), to be used for the treatment of cystinuria, a rare inherited disorder that causes a buildup of cystine levels in the urine resulting in the formation of recurring cystine kidney stones. Thiola EC is expected to be available in July 2019.

“The approval of Thiola EC marks another step in our continued commitment to helping patients with cystinuria manage the threat of recurring cystine stones,” said Eric Dube, Ph.D., chief executive officer of Retrophin. “This new formulation provides patients with the freedom to administer Thiola EC with or without food, an advancement over the original formulation which has limiting food restrictions, and also provides the potential to reduce the number of tablets necessary to manage cystinuria. We look forward to working with the cystinuria community as we make the new formulation available next month.”

The recommended initial dosage of Thiola in adult patients is 800 mg per day and in clinical studies the average dose of Thiola was approximately 1,000 mg, or 10 pills per day. The original formulation of Thiola 100 mg is recommended to be administered at least one hour before or two hours after meals. Thiola EC 100 mg and 300 mg tablets are recommended to be administered with or without food.

“Thiola’s utility as the treatment of choice for cystinuria is well established. However, for certain patients, the challenges of administration one hour before or two hours after meals three times a day, coupled with a high pill burden, have been challenging,” said Dr. David S. Goldfarb, Clinical Chief, Division of Nephrology at NYU Langone Health. “Having a new treatment option with the flexibility of dosing with or without food, as well as one that provides an opportunity for patients to take fewer pills, should meaningfully improve convenience and compliance.”

Thiola EC tablets were approved through the 505(b)(2) regulatory pathway which allows the FDA to reference previous findings of safety and efficacy for an already-approved product, combined with reviewing findings from further studies of the product.

About Thiola EC (tiopronin)

Thiola EC (tiopronin) is indicated, in combination with high fluid intake, alkali, and diet modification for the prevention of cystine stone formation in adults and pediatric patients ≥20 kg with severe homozygous cystinuria, who are not responsive to these measures alone.

https://www.drugbank.ca/drugs/DB06823

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

https://pubchem.ncbi.nlm.nih.gov/compound/5483

Ipsen Announces U.S. FDA Approval for Newly Designed Pre-Filled Syringe for Somatuline Depot (lanreotide)

 

Ipsen Biopharmaceuticals, an affiliate of Ipsen , announced today that the United States Food and Drug Administration (FDA) has approved a new pre-filled syringe for Somatuline Depot (lanreotide). The syringe includes updated features, such as larger flanges, designed to help make it easier for healthcare providers to administer the injection.1 The indications remain the same as those for the previous pre-filled syringe and include the treatment of adult patients with unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival; treatment of adults with carcinoid syndrome; when used, it reduces the frequency of short-acting somatostatin analog rescue therapy; and the long-term treatment of patients with acromegaly who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option. Please see Important Safety Information below and accompanying full Prescribing Information.

“The conditions of GEP-NETs and acromegaly can be associated with a number of uncomfortable and unpleasant symptoms, and innovation aimed at improving the injection process is a step forward,” said Daphne Adelman, Clinical Nurse Specialist, Northwestern University, Chicago, and one of the authors of the study.

Ipsen conducted five separate but complementary studies in partnership with patients, their caregivers, nurses and other healthcare professionals to better understand the current use of the existing Somatuline® Depot pre-filled syringe and to evaluate ways to improve the features of the device.1 The result of this collaboration is a redesigned delivery system intended to make it easy to grip the syringe and administer the injection. The new syringe features a needle shield removal system, more stable plunger and thermoform tray that has recessed areas designed to help prevent accidental plunger depression. The built-in safety system, which may help to prevent needle stick injury by locking in place following the administration, has not been changed.

“We consistently look for opportunities to respond to the needs of the communities we serve, and this approval would not have been possible without the direct involvement of nurses and the patients with GEP-NETs and acromegaly whom they treat,” said Bradley Bailey, SVP, and Franchise Head Oncology/Endocrinology Business Unit at Ipsen. “We listened and collaborated to enhance the existing pre-filled syringe, making it sturdier for healthcare providers when administering treatment, with the intention of improving the injection process. We look forward to bringing this innovation to healthcare providers for their patients soon.”

The new pre-filled syringe is for deep subcutaneous injection and is intended for administration by a healthcare professional. Healthcare providers can expect to receive the new syringe during Q3 2019. The device is approved for use in the U.S., EU and additional ex-U.S. markets.

Dova Pharmaceuticals Announces FDA Approval of Doptelet (avatrombopag) for Treatment of Chronic Immune Thrombocytopenia (ITP)

In continuation of my update on avatrombopag

Dova Pharmaceuticals, Inc.  a pharmaceutical company focused on acquiring, developing and commercializing drug candidates for diseases where there is a high unmet need, today announced the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) that expands the use of Doptelet (avatrombopag) to include the treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. 

Doptelet is also FDA-approved for the treatment of thrombocytopenia in adult patients with chronic liver disease (CLD) who are scheduled to undergo a procedure.  Earlier this week, Dova announced the marketing authorization granted by the European Commission for Doptelet for the treatment of severe thrombocytopenia in adult patients with CLD who are scheduled to undergo an invasive procedure.

“Dova is pleased to provide Doptelet to patients and physicians in the United States for the treatment of chronic ITP in adult patients who have had an insufficient response to a previous treatment,” said Dr. David Zaccardelli, president and CEO of Dova. “In addition to offering patients with ITP a new treatment option, we expect Doptelet will also address an important unmet medical need in the market.  We sincerely thank the patients and dedicated researchers who participated in our clinical program as well as FDA for their collaboration during the review of this application.”

Doptelet is an oral, thrombopoietin receptor agonist (TPO-RA) administered with food.  In the pivotal Phase 3 study, Doptelet administration resulted in a platelet count of at least 50,000 per µL at day eight of therapy in the majority of patients, with efficacy superior to placebo in maintaining platelet counts in the target range during the 6-month treatment period.  Additional supportive efficacy data for the ITP sNDA were provided by two Phase 2 ITP clinical trials, as well as two Phase 3 trials for the treatment of thrombocytopenia in patients with CLD. 

Safety data for 128 patients with ITP, and more than 1,000 subjects treated across 24 studies in the Doptelet clinical development program across multiple indications, support the safety and tolerability of Doptelet. 

“ITP patients should work with their clinician to choose a therapy that supports their lifestyle and aims to achieve the best possible result to treat their ITP. That’s why having additional treatment options are so important,” said Caroline Kruse, president and CEO of the Platelet Disorder Support Association, a patient advocacy organization dedicated to ITP patients. “We are thrilled to have a new, oral TPO-RA available for adult patients with ITP.  Every new treatment provides more choices and new hope to our community.”

Dova is committed to enabling patient access to Doptelet.  Doptelet will be priced similarly to other TPO-RAs used to treat ITP, and Dova will continue to offer Patient Assistance and Co-Pay programs. The commercial launch of Doptelet for ITP is anticipated to occur in mid-July 2019. 

Dova also entered into an expanded partnership in the United States with Salix. Starting on July 1, 2019, in addition to the gastroenterology, colorectal surgery, and proctology segments, Salix will have the exclusive right to co-promote the CLD indication for Doptelet to the hepatology and interventional radiology segments.  Dova will continue to pay Salix a commission based on a percentage of net sales in these specialties, which will be in the mid-thirties beginning on July 1, 2019.  In addition, the co-promotion agreement was extended to September 2023.

Dr. Zaccardelli added, “The expanded partnership with Salix builds additional momentum for Doptelet and enables the Dova team to focus on a successful launch of the ITP indication. As a growing leader in the treatment of thrombocytopenia, we are committed to realizing Doptelet’s significant market opportunity in CLD, ITP and potentially chemotherapy-induced thrombocytopenia (CIT) for which we expect Phase 3 trial top-line results in the first half of 2020.”

https://pubchem.ncbi.nlm.nih.gov/compound/AVATROMBOPAG#section=3D-Conformer

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

Experimental Drug, Voxelotor, Shows Early Promise Against Sickle Cell Disease

An experimental drug for sickle cell disease reduced anemia and boosted the health of red blood cells in patients, according to a new study.

Whether the drug, voxelotor, will have long-term health benefits to patients remains to be seen.

But if approved for use by the U.S. Food and Drug Administration, "people living with sickle cell disease might have a new, once daily, tolerable oral medication that increases their hemoglobin level in the near future," noted Dr. Banu Aygun, who wasn't involved in the new trial.

She is associate chief of hematology at Cohen Children's Medical Center in New Hyde Park, N.Y.

As Aygun explained, sickle cell disease is an inherited blood disorder affecting more than 100,000 Americans. Black Americans, especially, are prone to the illness.

"The disease is the result of a change in a single gene leading to the production of an abnormal hemoglobin called sickle hemoglobin [HbS]," Aygun said.

"Due to this abnormal hemoglobin, red blood cells take the shape of a sickle and die much sooner than normal red blood cells. The sickle cells block small blood vessels, causing pain and affecting many organs throughout the body, leading to premature death," she said.

Right now, patients with sickle cell -- many of them children -- have few treatment options. "So far, there are only two FDA-approved drugs for sickle cell disease: hydroxyurea and glutamine," Aygun noted.

The new 17-month, phase 3 clinical trial was designed to see if a third treatment might be on the horizon. It was funded by voxelotor's maker, Global Blood Therapeutics, and included 274 patients, ages 12 to 65, in 12 countries.

Patients were divided into three groups that received either a 900-mg or 1,500-mg daily dose of the drug voxelotor, or a "dummy" placebo pill.

The study found that 51% of patients who took the higher dose of voxelotor had a significant increase in their hemoglobin levels after six months of treatment, compared with 7% of those who received the placebo.

Another finding was that 41% of patients who took the higher dose of the drug reached hemoglobin levels of more than 10g/dl at 24 weeks. A normal, non-anemic hemoglobin count ranges between 11.5 to 17.5 g/dl, depending on age and gender, the study authors noted.

"Chronic organ failure, which is predicted by the severity of anemia, is a leading cause of death for patients with sickle cell disease," said study lead researcher Dr. Elliott Vichinsky, a professor at the University of California, San Francisco.
"These patients are susceptible to strokes, renal failure and other complications that lead to early death," he said in a UCSF news release. "We believe this drug has the potential to decrease chronic organ failure in patients with this condition."

For her part, Aygun said the new drug does seem to hold promise, but gains for patients were so far not dramatic.

She noted that patient pain "events" didn't change, regardless of whether people received voxelotor or the placebo. The most common side effects with the new drug were headache and diarrhea.

And Aygun stressed that it remains to be seen "whether taking this medication for longer duration will lead to a decrease in pain events or organ damage caused by sickle cell disease."

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

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

FDA Approval of Xofluza (baloxavir marboxil) for High Risk of Developing Influenza-Related Complications

 Genentech, a member of the Roche Group,  announced that the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for Xofluza™ (baloxavir marboxil) for the treatment of acute, uncomplicated influenza, or flu, in people 12 years of age and older who have been symptomatic for no more than 48 hours and who are at high risk of developing flu-related complications. Xofluza is a first-in-class, one-dose oral medicine with a novel proposed mechanism of action that inhibits polymerase acidic endonuclease, an enzyme essential for viral replication.

"With the flu season rapidly approaching, we can now offer Xofluza as the first and only FDA-approved treatment option indicated specifically for those at high risk of flu complications," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “People with chronic conditions such as asthma, heart disease and diabetes are at higher risk of developing serious complications from the flu, so it is critical that these patients speak with their healthcare providers about possible treatment at the first signs and symptoms of the disease.”

The flu has the potential to cause a variety of complications, ranging from sinus or ear infections to more serious complications such as pneumonia. This expanded indication for Xofluza was approved based on results from the Phase III CAPSTONE-2 study of a single dose of 40 mg or 80 mg of Xofluza compared to oseltamivir (75 mg twice daily for five days), or placebo in people 12 years of age or older who met CDC criteria for being at high risk of complications from the flu. Xofluza significantly reduced the time to improvement of flu symptoms compared to placebo, including in people infected with the flu type B virus. Adverse events reported in at least 1% of adult and adolescent subjects treated with Xofluza included diarrhea (3%), bronchitis (3%), nausea (2%), sinusitis (2%) and headache (1%).

Xofluza is currently approved in several countries for the treatment of flu types A and B. In October 2018, Xofluza was first approved by the FDA for the treatment of acute, uncomplicated flu in otherwise healthy people 12 years of age and older who have been symptomatic for no more than 48 hours, representing the first new antiviral to treat the flu in the U.S. in 20 years.

About CAPSTONE-2

CAPSTONE-2 is a Phase III, multicenter, randomized, double-blind study that evaluated a single dose of Xofluza compared with placebo and oseltamivir in people 12 years of age or older who are at a high risk of complications from the flu. The Centers for Disease Control and Prevention (CDC) defines people at high risk of serious flu complications as those who have conditions such as asthma, chronic lung disease, diabetes, heart disease, morbid obesity or adults 65 years of age or older. The study was conducted globally by Shionogi & Co., Ltd.

Participants enrolled in the study were randomly assigned to receive a single dose of 40 mg or 80 mg of Xofluza, placebo or 75 mg of oseltamivir twice a day for five days. The primary objective of the study was to evaluate the efficacy of a single dose of Xofluza compared with placebo by measuring the time to improvement of flu symptoms. Key findings from the study found that:

Xofluza significantly reduced the time to improvement of flu symptoms versus placebo in people at high risk of complications from the flu (median time 73 hours versus 102 hours; p<0.001). Similar efficacy results were seen between Xofluza and oseltamivir in relation to duration of symptoms (median time 73 hours versus 81hours). In subjects infected with type B virus, the median time to improvement of flu symptoms was shorter in the Xofluza group compared to the placebo group (75 hours versus 101 hours respectively). Adverse events reported in at least 1% of adult and adolescent subjects treated with Xofluza included diarrhea (3%), bronchitis (3%), nausea (2%), sinusitis (2%) and headache (1%). Xofluza was well-tolerated and no new safety signals were identified.

About Xofluza ™ (baloxavir marboxil)

Xofluza is a first-in-class, one-dose oral medicine with a novel proposed mechanism of action that has demonstrated efficacy in a wide range of influenza viruses, including in vitro activity against oseltamivir-resistant strains and avian strains (H7N9, H5N1) in non-clinical studies. Unlike other currently available antiviral treatments, Xofluza is the first in a new class of antivirals designed to inhibit the cap-dependent endonuclease protein, which is essential for viral replication.