FDA Approves Fotivda (tivozanib) for the Treatment of Adult Patients with Relapsed or Refractory Advanced Renal Cell Carcinoma

In continuation of my update on Tivozanib

AVEO Oncology (Nasdaq: AVEO)   announced  the U.S. Food and Drug Administration (FDA)   approval of  Fotivda (tivozanib) for the treatment of adults with relapsed or refractory advanced renal cell carcinoma (RCC) who have received two or more prior systemic therapies. Fotivda is an oral, next-generation vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI).

“Today’s approval of Fotivda provides a new tool for treating patients with kidney cancer who have relapsed or become refractory to two or more prior systemic therapies,” said Brian Rini, MD, Chief of Clinical Trials at Vanderbilt Ingram Cancer Center and principal investigator of the TIVO-3 trial. “With advances in RCC treatment, patients are living longer, increasing the need for proven, well tolerated treatment options in the relapsed or refractory setting. The TIVO-3 study is the first positive Phase 3 study in RCC patients who received two or more prior systemic therapies, and also the first Phase 3 RCC study to include a predefined population of patients who have received prior immunotherapy, the current standard of care in earlier-line treatment. With this approval, I believe Fotivda represents an attractive intervention, and expect it to play a meaningful role in the evolving RCC treatment landscape.”

“We believe in Fotivda’s potential to provide a differentiated treatment option for the growing number of individuals in the U.S. with relapsed or refractory RCC, and today marks the culmination of many years of hard work and determination of many individuals to bring this therapy to patients,” said Michael Bailey, president and chief executive officer of AVEO. “With today’s approval, AVEO begins its journey as a commercial-stage company, a noteworthy accomplishment in our industry. On behalf of the entire AVEO team, I would like to thank all the patients, their families, and caregivers whose tireless efforts made this day possible.”

“Relapsed or refractory RCC is a devastating disease for which patient outcomes can be limited due to the tradeoff between tolerability and efficacy,” said Dena Battle, president of KCCure. “The FDA approval of Fotivda represents an exciting, meaningful advancement by providing a new treatment option for this patient population.”

AVEO plans to make Fotivda available to patients in the U.S. by March 31, 2021.

The approval of Fotivda is based on AVEO’s pivotal Phase 3 study, TIVO-3, comparing Fotivda to sorafenib in relapsed or refractory advanced RCC following two or more prior systemic therapies. The application is also supported by three additional trials in RCC and includes safety data from over 1,000 clinical trial subjects.

Patients (n=350) enrolled in the TIVO-3 study were randomized 1:1 to receive either Fotivda or sorafenib. The main efficacy outcome measure was progression-free survival (PFS), assessed by a blinded independent radiology review committee. Other efficacy endpoints were overall survival (OS) and objective response rate (ORR).

Median PFS was 5.6 months (95% CI: 4.8, 7.3) in the Fotivda arm (n=175) compared with 3.9 months (95% CI: 3.7, 5.6) for those treated with sorafenib (HR 0.73; 95% CI: 0.56, 0.95; p=0.016). Median OS was 16.4 (95% CI: 13.4, 21.9) and 19.2 months (95% CI: 14.9, 24.2), for the Fotivda and sorafenib arms, respectively (HR 0.97; 95% CI: 0.75, 1.24). The ORR was 18% (95% CI: 12%, 24%) for the Fotivda arm and 8% (95% CI: 4%, 13%) for the sorafenib arm.

The most common (≥20%) adverse reactions were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis. The most common grade 3 or 4 laboratory abnormalities (≥5%) were decreased sodium, increased lipase, and decreased phosphate.

The recommended tivozanib dose is 1.34 mg once daily with or without food for 21 days every 28 days on treatment followed by 7 days off treatment (28 day cycle) until disease progression or unacceptable toxicity.

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

FDA Approves Kimyrsa (oritavancin) for the Treatment of Adult Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI)

Melinta Therapeutics, LLC (Melinta), a commercial-stage company focused on the development and commercialization of novel antibiotics, today announced that the U.S. Food and Drug Administration (FDA) has approved Kimyrsa (oritavancin)  for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of designated Gram-positive microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA). Kimyrsa is a lipoglycopeptide antibiotic that delivers a complete course of therapy for ABSSSI in a single, one hour 1,200 mg infusion.

“The approval of Kimyrsa demonstrates Melinta’s commitment to provide innovative therapies to patients with acute and life-threatening illnesses,” said Christine Ann Miller, President and Chief Executive Officer of Melinta. “We have responded to the requests of the medical community to provide an oritavancin product with a shorter infusion time.  We believe that with the approval of Kimyrsa and product availability this summer, physicians and patients will now have a compelling new one-dose alternative to the current standard of multi-dose regimens for ABSSSI.”

ABSSSI affect approximately 14 million patients in the U.S. each year, are responsible for over 3 million visits to the Emergency Room annually and represent the 8th most common cause of Emergency Department hospital admissions1,2. ABSSSI cost U.S. hospitals $4 billion each year, with a 4.1-day average length of stay for hospitalized ABSSSI patients.2

“Kimyrsa is an important new treatment option that will provide clinicians with additional flexibility to treat ABSSSI patients in multiple care settings, without the need for hospitalization,” said Andrew Dold, D.O., member of a private infectious disease practice covering the Greater Atlanta Region. “Single-dose, long-acting antibiotics, such as Kimyrsa, may be especially beneficial for patients who lack the support or resources to adhere to multiple intravenous administrations.”

The efficacy and safety of Kimyrsa were established in the SOLO clinical trials with another oritavancin product, Orbactiv. The SOLO trials were randomized, double-blind, multicenter studies that evaluated a single 1,200 mg IV dose of oritavancin against twice-daily vancomycin for the treatment of ABSSSI in 1,987 adult patients and assessed one of the largest subsets of documented MRSA infection (405 patients). These trials demonstrated that 1,200 mg one-dose IV oritavancin infusion was as effective as 7-to-10 days of twice-daily vancomycin (1 g or 15 mg/kg) for the primary and secondary endpoints.  Kimyrsa approval is based on the results of an open-label, multi-center, pharmacokinetics study, which compared Kimyrsa administered over 1 hour (N=50) to Orbactiv administered over 3 hours (N=52) for the treatment of adult patients with ABSSSI.

Michael Waters, M.D. and lead investigator in the PK clinical trial stated, “Kimyrsa was shown to be comparable to Orbactiv with a favorable safety profile.  I’m pleased that these outcomes support the approval of Kimyrsa to provide oritavancin with a shorter infusion time and lower infusion volume.  With these features, Kimyrsa can further enhance the treatment experience for the patient and efficiency of administration in clinical practice.”

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

FDA Approves Gemtesa (vibegron) Tablets for the Treatment of Patients with Overactive Bladder (OAB)

Urovant Sciences (Nasdaq: UROV) announced    the U.S. Food and Drug Administration (FDA)  approval of  the New Drug Application (NDA) for once-daily 75 mg Gemtesa (vibegron), a beta-3 adrenergic receptor (β3) agonist, for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence (UUI), urgency, and urinary frequency in adults. This approval marks the first new oral branded OAB medication approved by the FDA since 2012, and it is the first product approval for Urovant Sciences.

“The FDA’s approval of Gemtesa is an important milestone for the tens of millions of patients living with overactive bladder and for Urovant, as it is our first drug approval. We look forward to launching Gemtesa in the coming months and believe that it will provide a compelling alternative for the many patients suffering from the burden of an overactive bladder. We also remain committed to bringing more new therapies to market that address unmet medical needs of patients suffering from urologic diseases,” said Jim Robinson, president and chief executive officer of Urovant Sciences.

“The clinical data for once-daily 75 mg Gemtesa demonstrated clear efficacy on the key symptoms of OAB by reducing urinary frequency, urge urinary incontinence, and urgency. In addition, data specifically showing reduction in urgency episodes are included in the Prescribing Information of Gemtesa, which is unique among currently-available OAB treatments. Urgency episode reduction data are particularly relevant for OAB patients and their health care providers, as they show Gemtesa’s direct impact on a hallmark symptom of the condition,” said Cornelia Haag-Molkenteller, M.D., Ph.D., chief medical officer of Urovant Sciences. “By successfully treating clinical symptoms, Gemtesa may allow patients to overcome the devastating impact that OAB can have on their daily lives.”

Gemtesa is an oral, once-daily tablet containing 75 mg of vibegron, a small-molecule β3 agonist which helps relax the detrusor bladder muscle so that the bladder can hold more urine, thereby reducing symptoms of OAB.

“Gemtesa is the first beta 3-agonist available as a once-daily pill which does not require dose titration,” said David Staskin, MD, clinical trial investigator and a leading urologist with St. Elizabeth’s Medical Center in Boston. “Notably, Gemtesa did not have any increase in the adverse event of hypertension compared to placebo in the key EMPOWUR study and has no interactions with medications metabolized by CYP2D6, which is important since many common medications are metabolized by CYP2D6.”

The FDA’s approval is based on results from an extensive development program involving more than 4,000 OAB patients, including the 12-week double blind, placebo-controlled Phase 3 EMPOWUR study with a dose of 75 mg and the double blind EMPOWUR long term extension study.1 These data show that treatment with Gemtesa resulted in statistically significant reductions in daily UUI, micturitions, and urgency episodes and an increase in the volume voided when compared to placebo in EMPOWUR.

The most common adverse reactions of Gemtesa from the double blind, placebo-controlled EMPOWUR study in ≥2% of patients were headache, nasopharyngitis, diarrhea, nausea, and upper respiratory tract infection. Gemtesa demonstrated the same rates for the adverse events of hypertension and increased blood pressure as placebo.

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

FDA Approves Gemtesa (vibegron) Tablets for the Treatment of Patients with Overactive Bladder (OAB)

FDA Approves Orladeyo (berotralstat) as the First Oral, Once-Daily Therapy to Prevent Attacks in Hereditary Angioedema Patients

BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX)  announced the U.S. Food and Drug Administration (FDA) approval of  oral, once-daily Orladeyo (berotralstat) for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 12 years and older.

“Orladeyo offers people with HAE and their physicians the first orally administered non-steroidal option for preventing HAE attacks and represents an important and welcome step in making more treatment options available to physicians and patients,” said Anthony J. Castaldo, president and chief executive officer of the US Hereditary Angioedema Association (HAEA). 

In the pivotal Phase 3 APeX-2 trial, Orladeyo significantly reduced attacks at 24 weeks, and this reduction was sustained through 48 weeks. HAE patients who completed 48 weeks of treatment (150 mg) saw reductions in their HAE attack rates, from a mean of 2.9 attacks per month at baseline to a mean of 1.0 attacks per month after 48 weeks of therapy. In the long-term open label APeX-S trial, patients completing 48 weeks of therapy (150 mg) had a mean attack rate of 0.8 attacks per month.

Orladeyo was safe and well tolerated in both trials. The most frequently reported adverse reactions in patients receiving Orladeyo compared with placebo were gastrointestinal reactions. These reactions generally occurred early after initiation of treatment with Orladeyo, became less frequent with time and typically self-resolved.

“Patients and physicians acknowledge that HAE treatments can add a burden to patients’ lives.  As an oral, once-daily option, Orladeyo can provide significant attack reduction and lessen the burden associated with injections and infusions,” said Marc Riedl, M.D., professor of medicine and clinical director, U.S. Hereditary Angioedema Association Center at the University of California, San Diego, and an investigator in the APeX-2 trial.

“With this new treatment option, physicians and patients can continue to have collaborative discussions to choose the treatment that meets each patient’s needs, life circumstances and preferences,” Riedl added.

HAE patients note a significant treatment burden associated with existing prophylactic therapy. In addition to reducing HAE attack rate, data from APeX-2 show that patients reported meaningful improvements in both quality of life and overall patient-reported satisfaction, and significant reductions in their monthly use of standard of care on-demand medicine, while taking oral, once-daily Orladeyo (150 mg).2,3

“The FDA approval of Orladeyo fulfills a promise BioCryst made to HAE patients that we were committed to helping them achieve the dream of an oral, once-daily medicine to prevent and reduce the burden of their attacks,” said Jon Stonehouse, president and chief executive officer of BioCryst.

“Thank you to the HAE patients who participated in our clinical trials, to the investigators around the world who conducted these trials, to the HAEA for their patient advocacy and to our employees who never forgot that patients were waiting. We will stay focused on enabling access and providing personalized support to HAE patients and physicians,” Stonehouse added.

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

FDA Approves Orladeyo (berotralstat) as the First Oral, Once-Daily Therapy to Prevent Attacks in Hereditary Angioedema Patients

FDA Approves Sutab (sodium sulfate, magnesium sulfate, and potassium chloride) Tablets for Colonoscopy Preparation

Sebela Pharmaceuticals®  announced  the U.S. Food and Drug Administration (FDA) approval of  Sutab® (sodium sulfate, magnesium sulfate, and potassium chloride) tablets. Sutab, a sulfate-based tablet preparation for colonoscopy, was developed and will be marketed by Braintree Laboratories, the makers of SUPREP® Bowel Prep Kit (sodium sulfate, potassium sulfate and magnesium sulfate) Oral Solution—the market leader in branded colonoscopy preparations.1 Sutab gives patients and physicians an alternative to liquid-based colonoscopy preparations. Braintree, a leader in gastroenterology, is part of Sebela Pharmaceuticals.

Colonoscopy is the most common detection method for colorectal cancer, a leading cause of cancer-related deaths that can be managed more effectively through screening.2  It is considered the gold standard of colorectal cancer screening methods for its ability to view the entire colon and both detect and remove polyps during the same procedure.3,4 Nineteen million colonoscopies are performed in the U.S. every year.5 For those patients, particularly those who have had difficulty completing colonoscopy preparation in the past, Sutab presents a welcome alternative to liquid bowel preparation.

"Successful bowel prep is critical for gastroenterologists to clearly see any polyps or abnormalities, yet the immense volume of liquid prep solutions can prevent patients from adequately completing their regimens. Tablets provide a welcome alternative for successful prep completion and visualization of the colon," said Douglas K. Rex, M.D., Director of Endoscopy at Indiana University Hospital and Professor, Department of Medicine, Division of Gastroenterology and Hepatology, University of Indiana School of Medicine.

Alan Cooke, President and CEO of Sebela Pharmaceuticals, said, "Gastroenterologists and their patients have repeatedly asked for a safe and efficacious tablet bowel prep. Now patients can benefit from SUTAB, thanks to Braintree's innovative and dedicated team, who have worked tirelessly to develop this important product.  SUTAB's FDA approval underscores Braintree's more than 35-year commitment to gastroenterology."

In two pivotal trials, 92% of patients achieved successful bowel cleansing with SUTAB6 and 92%-95% of patients achieved successful cleansing in all segments of the colon, including the proximal colon. 7 In one pivotal trial, 91% of patients rated Sutab as very easy to tolerable to consume.7 Seventy-eight percent said they would request Sutab again for a future colonoscopy.7  Fifty-two percent of all Sutab and MoviPrep®8 patients reported at least one selected gastrointestinal adverse reaction. 6 More SUTAB patients reported experiencing nausea and vomiting than the comparator, with ≤1% of these reports considered severe. 6

"The approval of Sutab provides a welcome relief for patients who struggle with the unpleasant taste issues commonly associated with other products for colonoscopy preparation," said Jack A. Di Palma, M.D., Professor of Medicine and Fellowship Program Director of the Division of Gastroenterology at the University of South Alabama College of Medicine and Past-President of the American College of Gastroenterology. "And because SUTAB contains the active sulfate ingredients similar to SUPREP, gastroenterologists will already be familiar with its effects."

FDA Approves Sutab (sodium sulfate, magnesium sulfate, and potassium chloride) Tablets for Colonoscopy Preparation

FDA Approves Xaracoll (bupivacaine hydrochloride) Implant for Acute Postsurgical Pain Relief Following Open Inguinal Hernia Repair

In continuation of my update on bupivacaine 

Innocoll Holdings Limited, a specialty pharmaceutical company and portfolio business of Gurnet Point Capital, announced today that the US Food and Drug Administration (FDA) has approved Xaracoll  for acute postsurgical pain relief for up to 24 hours in adults following open inguinal hernia repair, a painful and commonly-performed surgery.1  

Xaracoll is a unique, non-injectable drug-device combination in the form of a fully bioresorbable collagen implant containing bupivacaine hydrochloride. Xaracoll is placed directly into the surgical site during surgery and, after placement, releases bupivacaine immediately and over time.1,2

“Xaracoll is an advancement in the management of postsurgical pain as it is the first and only drug-device combination product to provide local pain relief following open inguinal hernia repair in adults,” said Innocoll CEO Rich Fante. “The FDA approval is an important milestone for Innocoll and we are excited to bring Xaracoll to market later this year as an effective and well-tolerated, non-opioid treatment option for surgeons.”

The efficacy and safety of Xaracoll was evaluated in two Phase III studies of identical design in open inguinal hernia repair. The Phase III studies were performed as outpatient surgeries in adults across 39 sites (N=610, Xaracoll Arm N=404, Placebo Arm N=206) in the US. Xaracoll provided statistically significant pain relief through 24 hours versus placebo, the primary endpoint for both studies. The first secondary endpoint of total use of opioid analgesia through 24 hours was also statistically significant. Additionally, the proportion of patients who did not receive opioid rescue analgesia through 72 hours in the Xaracoll and placebo treatment groups was 36% and 22%, respectively, in Study 1, and 28% and 12%, respectively, in Study 2.  The median time to first opioid rescue analgesia in the Xaracoll and placebo treatment groups was 11 hours and 1 hour, respectively, in Study 1, and 6 hours and 1 hour, respectively in Study 2. The most common adverse reactions in clinical trials (incidence ≥2% and higher than placebo) included incision site swelling, dysgeusia, headache, tremor, blurred vision, seroma, scrotal swelling, pyrexia, oral hypoesthesia, and post procedural discharge.1,3

“In Phase III studies Xaracoll was shown to provide local pain relief in patients undergoing open inguinal hernia repair while also decreasing the amount of opioids needed,” said Wendy Niebler DO, MBA, Chief Medical Officer at Innocoll. “We look forward to sharing our Phase III data with surgeons as we introduce this new option to manage acute pain following open inguinal hernia repair in adults.”  

INDICATIONS AND USAGE

Xaracoll contains an amide local anesthetic and is indicated in adults for placement into the surgical site to produce postsurgical analgesia for up to 24 hours following open inguinal hernia repair.

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

FDA Approves Xaracoll (bupivacaine hydrochloride) Implant for Acute Postsurgical Pain Relief Following Open Inguinal Hernia Repair

FDA Approves Winlevi (clascoterone) Cream for the Treatment of Acne

Cassiopea SpA (SIX: SKIN),  announced   the United States Food and Drug Administration (FDA) approval of  Winlevi (clascoterone cream 1%) for the treatment of acne in patients 12 years and older. Notwithstanding acne being the most prevalent skin condition in the U.S. affecting up to 50 million Americans annually1, the last FDA approval of an acne drug with a new mechanism of action (MOA) occurred nearly 40 years ago.

Acne is a multifactorial skin condition, affected by four distinct pathways: excess oil (sebum) production, clogged pores (hyperkeratinization), bacteria growth (C. acnes), and inflammation2. Topical treatment options that target androgens, which largely drive sebum production and inflammation, presented a significant unmet need in the acne treatment market until now.

“The approval of Winlevi is an exciting breakthrough in acne treatment. This game-changing topical drug offers a non-antibiotic approach to people with acne, by targeting the androgen receptors directly in the skin. It fills a longstanding gap in acne therapy.” said Michael Gold, M.D., Investigator and Medical Director, Gold Skin Care Center and Tennessee Clinical Research Center. “After 40 years, it provides a much-anticipated, complementary new approach to treat acne.”

Cassiopea’s first-in-class topical androgen receptor inhibitor, Winlevi, tackles the androgen hormone component of acne in both males and females. Androgen receptor inhibitors act by limiting the effects of these hormones on increasing sebum production and inflammation3.

In pivotal clinical trials, Winlevi demonstrated treatment success and reductions in acne lesions and was well tolerated when used twice a day. The most frequently observed local skin reaction was mild erythema4,5.

Diana Harbort, CEO of Cassiopea, said: “This milestone approval marks the introduction of a new class of topical medication in Dermatology. Dermatologists have said targeting androgen hormonal activity in the skin is ‘the holy grail’ of acne treatment for both males and females. We are proud to bring this new innovation to acne patients. This approval rewards many years of hard work and positions Cassiopea as a leader in Dermatology. Now we look forward to expanding our franchise and advancing our next investigational drug candidate for androgenetic alopecia.”

Winlevi is expected to be available in the United States in early 2021. Complete prescribing information is available on www.WINLEVI.com.

About Winlevi (clascoterone cream 1%)

Winlevi (clascoterone cream 1%) is approved for the treatment of acne vulgaris in people aged 12 and older. Although Winlevi’s exact mechanism of action is unknown, laboratory studies suggest the active ingredient, clascoterone, competes with androgens, specifically dihydrotestosterone (DHT), for binding to the androgen receptors within the sebaceous gland and hair follicles6.

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

FDA Approves Winlevi (clascoterone) Cream for the Treatment of Acne

FDA Approves Durysta (bimatoprost implant) to Lower Intraocular Pressure In Open-Angle Glaucoma or Ocular Hypertension Patients

Allergan plc (NYSE: AGN), a leading global pharmaceutical company with more than 70 years of heritage in eye care, announced the U.S. Food and Drug Administration (FDA) approval.  With this approval, Durysta becomes the first intracameral, biodegradable sustained-release implant indicated to reduce intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).

"Today's FDA approval marks a breakthrough milestone for the glaucoma community and provides a much-needed option for patients challenged with topical drops or needing alternative options," said David Nicholson, Chief Research and Development Officer, Allergan. "At Allergan, our mission is to contribute meaningful strategies that help preserve people's vision, while ensuring that therapies are mindful of the realities of administration and compliance. As a commitment to the ongoing development of this innovation, Allergan has five ongoing Phase 3 studies with Durysta to support further potential FDA label enhancement and rest of the world approvals."

The FDA approval is based on results from the two 20-month (including 8-month extended follow up) Phase 3 ARTEMIS studies evaluating 1,122 subjects on the efficacy and safety of Durysta versus twice daily topical timolol drops, an FDA accepted comparator for registrational clinical trials, in patients with OAG or OHT. In the two Phase 3 ARTEMIS studies, Durysta reduced IOP by approximately 30 percent from baseline over the 12-week primary efficacy period, meeting the predefined criteria for non-inferiority to the study comparator.

"Millions of people are living with glaucoma, one of the leading causes of vision loss; however, new treatment options are needed to help doctors and patients better manage this disease," said Felipe Medeiros , M.D., Ph.D., Distinguished Professor of Ophthalmology and Vice-Chair for Technology, Director Clinical Research Unit, Department of Ophthalmology, Duke University. "The ARTEMIS trials demonstrated that Durysta lowered IOP in patients by approximately 30 percent and demonstrated a duration of effect through the 12-week primary efficacy period. As the first FDA-approved intracameral, biodegradable sustained-release implant providing continuous drug delivery, Durysta has the potential to significantly shift the paradigm for treating glaucoma."

With the launch of Durysta, Allergan proudly expands availability of Allergan EyeCue®, a proven reimbursement service for eye care professionals to facilitate patient benefit verification, savings program enrollment for eligible patients, and prior authorization (PA) assistance for Allergan Eye Care products.

FDA Approves Tazverik (tazemetostat) for the Treatment of Patients with Epithelioid Sarcoma

Epizyme, Inc. (Nasdaq: EPZM), a biopharmaceutical company developing novel epigenetic therapies,  announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval of Tazverik (tazemetostat) for the treatment of adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection, based on overall response rate and duration of response in a Phase 2 clinical trial.

Despite industry advancements, there are limited therapeutic options for treating patients with epithelioid sarcoma who struggle with high rates of recurrence and toxicities associated with currently used therapies,” said Gary K. Schwartz, M.D., chief of hematology and oncology at Columbia University and NewYork-Presbyterian Hospital, deputy director of the Herbert Irving Comprehensive Cancer Center, professor of oncology at Columbia University Vagelos College of Physicians and Surgeons and an investigator in Epizyme’s Phase 2 trial. “The Tazverik data from the ES cohort in Epizyme’s Phase 2 trial support its potential to provide clinically meaningful and durable responses, and tolerability for ES patients. This approval of Tazverik represents an important advancement in the treatment of patients with ES.”

“Today’s accelerated approval of Tazverik is a landmark event for people with ES and represents our dedication to our mission of rewriting treatment for people with cancer and other serious diseases,” said Robert Bazemore, president and chief executive officer of Epizyme. “Tazverik is now the first and only FDA-approved EZH2 inhibitor, and the first and only FDA-approved treatment specifically indicated for ES patients. Our commercial launch plans are underway, and we expect to make Tazverik available to ES patients and treating physicians across the U.S. within 10 business days.”

“For people with epithelioid sarcoma, an aggressive life threatening cancer that affects young adults, having new treatment options can offer much needed hope,” added Denise Reinke, MS, NP, MBA, president and chief executive officer of the Sarcoma Alliance for Research through Collaboration (SARC) and co-founder of the Sarcoma Coalition.

Dr. Shefali Agarwal, chief medical officer, commented, “Discovering, developing and obtaining FDA approval for Tazverik, with its novel mechanism of action, is the result of years of work and commitment by many people, including the patients, caregivers and physicians who have participated in our clinical trials, along with the talented team at Epizyme. We are tremendously proud of this important milestone and look forward to further advancing clinical development of tazemetostat for multiple types of cancers.”

Continued approval for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial. The company’s ongoing, global, randomized, controlled confirmatory trial assessing the combination of Tazverik plus doxorubicin compared with doxorubicin plus placebo as a front-line treatment for ES is underway.

In addition, Epizyme will conduct certain post-marketing activities, including clinical pharmacology evaluations to assess the effect of Tazverik on liver function and the effect of CYP3A inhibitors and inducers on Tazverik to inform aspects of the prescribing information. The company will also expand enrollment in Cohort 6 of its Phase 2 study, which has enrolled 44 patients to date, for a total of at least 60 epithelioid sarcoma patients. This expansion is intended to provide more patient experience for potential future inclusion in the label.

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

FDA Approves Trijardy XR (empagliflozin/linagliptin/metformin) for Type 2 Diabetes in Adults

In continuation of my update on empagliflozin/linagliptin/metformin 

    

The U.S. Food and Drug Administration (FDA) has approved Trijardy XR (empagliflozin/linagliptin/metformin hydrochloride extended release tablets) to lower blood sugar in adults with type 2 diabetes, along with diet and exercise. Trijardy XR provides three type 2 diabetes medicines in one pill, including Jardiance® (empagliflozin), Tradjenta® (linagliptin) and metformin hydrochloride extended release. Trijardy XR is marketed by Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company (NYSE: LLY).

"Many adults living with type 2 diabetes who are already on a treatment plan including multiple medications still struggle to keep their blood sugar under control, and may require additional agents to reach their A1C targets," said Ralph DeFronzo, M.D., professor and diabetes division chief, UT Health San Antonio. "Adding new medicines to an individual's plan can be challenging for some, which is why new treatment options that can help improve blood sugar without the burden of an increased pill count are important. In addition, type 2 diabetes is a complex disease that often requires the use of multiple antidiabetic medications to improve glycemic control. Having three different diabetes medications in a single tablet is an important advance in diabetes treatment."

In the U.S., both Jardiance and Tradjenta are once-daily tablets used along with diet and exercise to lower blood sugar in adults with type 2 diabetes. Jardiance is also approved to reduce the risk of cardiovascular death in adults with type 2 diabetes who have known cardiovascular disease. Jardiance is not for people with type 1 diabetes or for people with diabetic ketoacidosis (increased ketones in the blood or urine). Tradjenta is not for people with type 1 diabetes or for the treatment of diabetic ketoacidosis. Tradjenta has not been studied in people with a history of pancreatitis and it is unknown if using Tradjenta increases the risk of developing pancreatitis in these people. 

"We are proud to offer Trijardy XR as a new once-daily option combining three well-established medicines, including an extended-release version of metformin, the most commonly prescribed initial treatment for type 2 diabetes, Jardiance, the most prescribed SGLT2 inhibitor, and Tradjenta, the only single-dose DPP-4 inhibitor," said Mohamed Eid, M.D., M.P.H., M.H.A., vice president, Clinical Development & Medical Affairs, Cardio-Metabolism & Respiratory Medicine, Boehringer Ingelheim Pharmaceuticals, Inc. "We believe Trijardy XR has the potential to help adults with type 2 diabetes conveniently manage their treatment, especially those who are taking other medications and working on the necessary lifestyle changes."

Trijardy XR is not recommended for people with type 1 diabetes or diabetic ketoacidosis (increased ketones in the blood or urine). Trijardy XR has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at an increased risk for the development of pancreatitis while using Trijardy XR. The labeling for Trijardy XR contains a warning for lactic acidosis, a rare but serious complication that can occur due to metformin accumulation, and is common to all products containing metformin.

The FDA approval of Trijardy XR is based on two randomized open-label trials that assessed the bioequivalence of empagliflozin, linagliptin and metformin hydrochloride extended release fixed-dose combination tablets and their individual components in healthy adults. The safety profile of Trijardy XR was found to be consistent with its individual components.

"The approval of Trijardy XR reflects our commitment to the diabetes community and to innovation that addresses evolving needs," said Jeff Emmick, M.D. Ph.D., vice president, Product Development, Lilly. "We developed Trijardy XR because many people with type 2 diabetes need help managing this complex condition without adding more pills to their treatment plan. We look forward to making this new option available soon."

Trijardy XR is not for people who have severe kidney problems, end stage renal disease, or are on dialysis, have a serious condition called metabolic acidosis or diabetic ketoacidosis (increased ketones in the blood or urine), or are allergic to Jardiance, Tradjenta, metformin, or any of the ingredients in Trijardy XR. There have been postmarketing reports of acute pancreatitis, including fatal pancreatitis, in patients taking linagliptin, a component of Trijardy XR. Take careful notice of potential signs and symptoms of pancreatitis. If pancreatitis is suspected, promptly discontinue Trijardy XR and initiate appropriate management. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using Trijardy XR.

Trijardy XR will be available in four different dosages, including: 5 mg empagliflozin/2.5 mg linagliptin/1000 mg metformin HCl extended-release; 10 mg empagliflozin/5 mg linagliptin/1000 mg metformin HCl extended-release; 12.5 mg empagliflozin/2.5 mg linagliptin/1000 mg metformin HCl extended-release; and 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin HCl extended-release.

What is Trijardy XR?

Trijardy XR is a prescription medicine that contains 3 diabetes medicines, empagliflozin (JARDIANCE), linagliptin (TRADJENTA), and metformin hydrochloride. Trijardy XR can be used along with diet and exercise to lower blood sugar in adults with type 2 diabetes, and in adults with type 2 diabetes who have known cardiovascular disease when empagliflozin (JARDIANCE), one of the medicines in Trijardy XR, is needed to reduce the risk of cardiovascular death.

Trijardy XR is not for people with type 1 diabetes, or for people with diabetic ketoacidosis (increased ketones in the blood or urine).

If you have had pancreatitis (inflammation of the pancreas) in the past, it is not known if you have a higher chance of getting pancreatitis while you take Trijardy XR.

https://www.drugs.com/history/trijardy-xr.html

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 Boxed Warning About Increased Risk of Blood Clots and Death with Higher Dose of Tofacitinib (Xeljanz, Xeljanz XR)

In continuation of my update on tofacitinib 

The U.S. Food and Drug Administration has approved new warnings about an increased risk of blood clots and of death with the 10 mg twice daily dose of tofacitinib (Xeljanz, Xeljanz XR), which is used in patients with ulcerative colitis. In addition, the approved use of tofacitinib for ulcerative colitis will be limited to certain patients who are not treated effectively or who experience severe side effects with certain other medicines. We approved these changes, including adding our most prominent Boxed Warning, after reviewing interim data from an ongoing safety clinical trial of tofacitinib in patients with rheumatoid arthritis (RA) that examined a lower and this higher dose of the medicine.

The 10 mg twice daily dose of tofacitinib is not approved for RA or psoriatic arthritis (PsA). This dose is only approved for ulcerative colitis for initial treatment and for long-term use in limited situations. While the increased risks of blood clots and of death were seen in patients taking this dose for RA, these risks may also apply to those taking tofacitinib for ulcerative colitis.

Tofacitinib works by decreasing the activity of the immune system; an overactive immune system contributes to RA, PsA, and ulcerative colitis. Tofacitinib was first approved in 2012 to treat adult patients with RA who did not respond well to the medicine methotrexate. In RA, the body attacks its own joints, causing pain, swelling, and loss of function. In 2017, we approved the medicine to treat patients with a second condition that causes joint pain and swelling, PsA, who did not respond well to methotrexate or other similar medicines. In 2018, we approved tofacitinib to treat ulcerative colitis, which is a chronic, inflammatory disease affecting the colon.

Patients should tell your health care professionals if you have a history of blood clots or heart problems, and talk to them about any questions or concerns. Stop taking tofacitinib and seek emergency medical attention right away if you experience any unusual symptoms, including those that may signal a blood clot such as:

• Sudden shortness of breath
• Chest pain that worsens with breathing
• Swelling of a leg or arm
• Leg pain or tenderness, or red or discolored skin in the painful or swollen leg or arm

Do not stop taking tofacitinib without first talking to your health care professional, as doing so can worsen your condition.

Health care professionals should discontinue tofacitinib and promptly evaluate patients with symptoms of thrombosis. Counsel patients about the risks and advise them to seek medical attention immediately if they experience any unusual symptoms, including those of thrombosis listed above. Reserve tofacitinib to treat ulcerative colitis for patients who have failed or do not tolerate tumor necrosis factor (TNF) blockers. Avoid tofacitinib in patients who may have a higher risk of thrombosis. When treating ulcerative colitis, use tofacitinib at the lowest effective dose and limit the use of the 10 mg twice daily dosage to the shortest duration needed (See Additional Information for Health Care Professionals for more recommendations).

When FDA first approved tofacitinib in 2012, we required a postmarketing clinical trial in patients with RA on background methotrexate, to evaluate the risk of heart-related events, cancer, and infections. The trial is studying two different doses of tofacitinib (5 mg twice daily, which is the currently approved dose for RA, and a higher, 10 mg twice daily dosage) in comparison to a TNF blocker. An interim analysis of the trial’s results found an increased occurrence of blood clots and of death in patients treated with tofacitinib 10 mg twice daily compared to patients treated with tofacitinib 5 mg twice daily or a TNF blocker. Based on these results, the 10 mg twice daily treatment was stopped and patients were allowed to continue treatment on 5 mg twice daily.

This safety trial is ongoing. Patients in the 5 mg twice daily group and the TNF blocker group continue to be followed. FDA will reassess these safety issues when the trial has completed and final, verified data are available. We will update the public when additional information is available.

The interim results of the trial, as of January 2019, have identified the following:

• 19 cases of blood clots in the lung out of 3,884 patient-years of follow-up in patients who received tofacitinib 10 mg twice daily, compared to 3 cases out of 3,982 patient-years in patients who received TNF blockers
• 45 cases of death from all causes out of 3,884 patient-years of follow-up in patients who received tofacitinib 10 mg twice daily, compared to 25 cases out of 3,982 patient-years in patients who received TNF blockers

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

FDA Approves Ruzurgi (amifampridine) for Children with Lambert-Eaton Myasthenic Syndrome

In continuation of my update on amifampridine

The U.S. Food and Drug Administration approved Ruzurgi (amifampridine) tablets for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in patients 6 years to less than 17 years of age. This is the first FDA approval of a treatment specifically for pediatric patients with LEMS. The only other treatment approved for LEMS is only approved for use in adults.

“We continue to be committed to facilitating the development and approval of treatments for rare diseases, particularly those in children,” said Billy Dunn, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “This approval will provide a much-needed treatment option for pediatric patients with LEMS who have significant weakness and fatigue that can often cause great difficulties with daily activities.”

LEMS is a rare autoimmune disorder that affects the connection between nerves and muscles and causes weakness and other symptoms in affected patients. In people with LEMS, the body’s own immune system attacks the neuromuscular junction (the connection between nerves and muscles) and disrupts the ability of nerve cells to send signals to muscle cells. LEMS may be associated with other autoimmune diseases, but more commonly occurs in patients with cancer such as small cell lung cancer, where its onset precedes or coincides with the diagnosis of cancer. LEMS can occur at any age. The prevalence of LEMS specifically in pediatric patients is not known, but the overall prevalence of LEMS is estimated to be three per million individuals worldwide.

Use of Ruzurgi in patients 6 to less than 17 years of age is supported by evidence from adequate and well-controlled studies of the drug in adults with LEMS, pharmacokinetic data in adult patients, pharmacokinetic modeling and simulation to identify the dosing regimen in pediatric patients and safety data from pediatric patients 6 to less than 17 years of age.

The effectiveness of Ruzurgi for the treatment of LEMS was established by a randomized, double-blind, placebo-controlled withdrawal study of 32 adult patients in which patients were taking Ruzurgi for at least three months prior to entering the study. The study compared patients continuing on Ruzurgi to patients switched to placebo. Effectiveness was measured by the degree of change in a test that assessed the time it took the patient to rise from a chair, walk three meters, and return to the chair for three consecutive laps without pause. The patients that continued on Ruzurgi experienced less impairment than those on placebo. Effectiveness was also measured with a self-assessment scale for LEMS-related weakness that evaluated the feeling of weakening or strengthening. The scores indicated greater perceived weakening in the patients switched to placebo.

The most common side effects experienced by pediatric and adult patients taking Ruzurgi were burning or prickling sensation (paresthesia), abdominal pain, indigestion, dizziness and nausea. Side effects reported in pediatric patients were similar to those seen in adult patients. Seizures have been observed in patients without a history of seizures. Patients should inform their health care professional immediately if they have signs of hypersensitivity reactions such as rash, hives, itching, fever, swelling or trouble breathing.

The FDA granted this application Priority Review and Fast Track designations. Ruzurgi also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

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

FDA Approves Ruzurgi (amifampridine) for Children with Lambert-Eaton Myasthenic Syndrome