RapidRx

U.S. Food and Drug Administration (FDA) has approved Stelara (ustekinumab) for the treatment of moderately to severely active Crohn’s disease in adults (18 years or older) who have failed or were intolerant to treatment with immunomodulators or corticosteroids but never failed treatment with a tumor necrosis factor (TNF) blocker, or who failed or were intolerant to treatment with one or more TNF blockers. Stelara is the first biologic therapy for Crohn’s disease targeting interleukin (IL)-12 and IL-23 cytokines, which play a key role in inflammatory and immune responses.

“Crohn’s disease is a complex condition to treat, and not all therapies work for every patient,” said William J. Sandborn, MD, Chief, Division of Gastroenterology, and Professor of Medicine, UC San Diego School of Medicine, and study investigator. “The FDA approval of Stelara represents an important advancement in treating patients with Crohn’s disease, as this therapy offers an alternate mechanism of action to induce and maintain clinical remission over time. Based on the results of the clinical development program, Stelara has the potential to benefit many adults living with Crohn’s disease.”

In clinical studies of patients who were either new to, experienced with, or failed biologic therapy (TNF blockers), between 34% (UNITI-1 study) and 56% (UNITI-2 study) of patients experienced relief from their Crohn’s disease symptoms in just six weeks after receiving the one-time intravenous (IV) infusion of Stelara. Noticeable improvement was observed as early as three weeks. Additionally, the majority of those who responded to induction dosing and continued treatment with Stelara subcutaneous maintenance doses every 8 weeks were in remission at the end of 44 weeks (52 weeks from initiation of the induction dose).

Stelara is the only treatment for Crohn’s disease that starts with a weight-based, one-time intravenous (IV) infusion induction dose (260 mg [55 kg or less], 390 mg [more than 55 kg to 85 kg], or 520 mg [more than 85 kg]) to help reduce symptoms, followed by 90 mg subcutaneous maintenance injections every 8 weeks to help keep the symptoms under control. The first dose of Stelara is an induction dose, administered intravenously, under the supervision of a healthcare professional. Subsequent maintenance doses are administered as a subcutaneous injection every 8 weeks, either by a healthcare professional or self-injected by the patient after proper training.

About Crohn’s Disease

Crohn’s disease is a chronic inflammatory condition of the gastrointestinal tract that affects approximately 700,000 Americans. Symptoms of Crohn’s disease can vary but often include abdominal pain and tenderness, frequent diarrhea, rectal bleeding, weight loss, and fever. Hospitalization is at times required for severe disease, to treat certain complications, and for surgery. There is currently no cure for Crohn’s disease.¹

About Stelara (ustekinumab)

Stelara is a prescription medicine used to treat moderately to severely active Crohn’s disease in adult patients (18 years and older) who have already taken other medicine that did not work well enough or they could not tolerate it.

SOURCE Janssen Biotech, Inc.

September 23, 2016 — The U.S. Food and Drug Administration today approved Amjevita (adalimumab-atto) as a biosimilar to Humira (adalimumab) for multiple inflammatory diseases. Amjevita is approved for the following indications in adult patients:

• moderately to severely active rheumatoid arthritis;
• active psoriatic arthritis;
• active ankylosing spondylitis (an arthritis that affects the spine);
• moderately to severely active Crohn’s disease;
• moderately to severely active ulcerative colitis; and
• moderate to severe plaque psoriasis.

Amjevita is also indicated for moderately to severely active polyarticular juvenile idiopathic arthritis in patients four years of age and older.

Health care professionals should review the prescribing information in the labeling for detailed information about the approved uses.

“This is the fourth FDA-approved biosimilar. The biosimilar pathway is still a new frontier and one that we expect will enhance access to treatment for patients with serious medical conditions,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research.

Biological products are generally derived from a living organism and can come from many sources, including humans, animals, microorganisms or yeast. A biosimilar is a biological product that is approved based on a showing that it is highly similar to an already-approved biological product and has no clinically meaningful differences in terms of safety, purity and potency (i.e., safety and effectiveness) from the reference product, in addition to meeting other criteria specified by law.

The FDA’s approval of Amjevita is based on review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data and other clinical safety and effectiveness data that demonstrates Amjevita is biosimilar to Humira. It has been approved as a biosimilar, not as an interchangeable product.

The most serious known side effects with Amjevita are infections and malignancies. The most common expected adverse reactions with Amjevita are infections and injection site reactions.

Like Humira, the labeling for Amjevita contains a Boxed Warning to alert health care professionals and patients about an increased risk of serious infections leading to hospitalization or death. The Boxed Warning also notes that lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor blockers, including adalimumab products. The drug must be dispensed with a patient Medication Guide that describes important information about its uses and risks.

Amjevita is manufactured by Amgen, Inc., of Thousand Oaks, California. Humira was approved in December 2002 and is manufactured by AbbVie Inc. of North Chicago, Illinois.

September 21, 2016 – Janssen Pharmaceuticals, Inc. (Janssen) announced today the U.S. Food and Drug Administration (FDA) has approved Invokamet XR – a once-daily, fixed-dose combination therapy of canagliflozin and metformin hydrochloride extended-release (XR)—for first-line use as an adjunct to diet and exercise to improve blood glucose control in adults with type 2 diabetes when treatment with the two medications is appropriate.[1] Invokamet XR combines Invokana (canagliflozin), the most prescribed sodium glucose co-transporter 2 (SGLT2) inhibitor, with more than 9 million U.S. prescriptions since launch,[2] and an XR formulation of metformin. Metformin is commonly prescribed as an initial therapy for the treatment of type 2 diabetes.

“Invokamet XR offers the convenience of once-daily dosing and provides physicians needed flexibility for tailoring treatment to the needs of type 2 diabetes patients, especially those with higher A1C levels,” said John Anderson, M.D.,* Frist Clinic, Nashville, Tenn. “As with Invokamet, physicians can prescribe the XR formulation to adults when they are first diagnosed with type 2 diabetes or as additional therapy for people whose A1C levels are not well controlled with either agent alone.”

Phase 3 studies have shown the combination of Invokana and metformin reduces A1C significantly more than metformin alone, sitagliptin plus metformin, or glimepiride plus metformin. Treatment with Invokana as an add-on to metformin also demonstrated greater reductions in the secondary endpoints of body weight and systolic blood pressure.

The approved indication for Invokamet XR aligns with current type 2 diabetes treatment guidelines from the American Association of Clinical Endocrinologists and American College of Endocrinology and from the American Diabetes Association, which recommend dual therapy for patients with higher A1C levels.[3],[4] Specifically, guidelines recommend dual therapy for patients who have an initial A1C level of 7.5 percent or higher[3] and for those who have an initial level below 7.5 percent and do not achieve an A1C treatment goal after about three months on single therapy, often metformin.4 In addition, dual or triple therapy is recommended as first-line therapy in asymptomatic patients with an initial A1C level above 9 percent.[3]

A1C is a measure of average blood glucose over the past two to three months; the American Diabetes Association recommends most adults with type 2 diabetes maintain A1C levels of 7 percent or less.[5]

“The approval of Invokamet XR is further evidence of our ongoing commitment to provide new treatment options for people with type 2 diabetes,” said Paul Burton, M.D., Ph.D., Vice President, Medical Affairs, Janssen. “Our Invokana portfolio now offers physicians even more choices for helping patients improve control of A1C levels and other important health measures, with numerous dosing options for monotherapy and for combination therapy with both metformin and metformin XR.”

Invokamet XR is available in four dosages, in tablets containing canagliflozin 50 milligrams (mg) or 150 mg, and metformin XR 500 mg or 1000 mg. The recommended dosing is two tablets once daily with the morning meal. The prescribing information for Invokamet XR also contains a boxed warning for lactic acidosis, a rare but serious complication that can occur due to metformin accumulation.[1]

Studies in healthy adults have demonstrated that administration of Invokamet XR results in the same levels of canagliflozin and metformin XR in the body as when corresponding dosages of the two medicines are administered as separate tablets. Canagliflozin works with the kidneys to help adults with type 2 diabetes lose some sugar through the process of urination, and metformin decreases the production of glucose in the liver and improves the body’s response to insulin. Invokamet XR should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.[1]

Invokamet, the first combination of an SGLT2 inhibitor and an immediate-release formulation of metformin available in the United States, was initially approved by FDA in August 2014 as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes not adequately controlled with metformin or canagliflozin, or who are already being treated with both medications separately. In May 2016, FDA expanded the Invokamet indication to include adults with type 2 diabetes who are not already being treated with canagliflozin or metformin and may benefit from dual therapy.

High and high-normal thyroid function is associated with increased risk of dementia, experts say.

Data analysis was done within the Rotterdam Study. A total of 9,446 subjects with a mean age of 65 years were included in the evaluation of the link between thyroid-stimulating hormone (TSH) and free thyroxine with dementia, cognition, and subclinical vascular brain disease by MRI. The subjects were followed-up for a mean duration of 8 years. During this period, 601 subjects developed dementia.

In both full and normal ranges of thyroid function, high TSH function was associated with dementia risk, independent of cardiovascular risk factors.

Subjects with higher free thyroxine were at greater risk of developing dementia. High TSH in older women was associated with decreased absolute 10-year dementia risk.

An association was seen between higher TSH and better global cognitive scores while thyroid function was not linked with to subclinical vascular brain disease.

The authors concluded that high and high-normal thyroid function may increase the risk of developing dementia.

September 19, 2016 — The U.S. Food and Drug Administration today approved Exondys 51 (eteplirsen) injection, the first drug approved to treat patients with Duchenne muscular dystrophy (DMD). Exondys 51 is specifically indicated for patients who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping, which affects about 13 percent of the population with DMD.

“Patients with a particular type of Duchenne muscular dystrophy will now have access to an approved treatment for this rare and devastating disease,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease and the lack of medical understanding of many disorders. Accelerated approval makes this drug available to patients based on initial data, but we eagerly await learning more about the efficacy of this drug through a confirmatory clinical trial that the company must conduct after approval.”

DMD is a rare genetic disorder characterized by progressive muscle deterioration and weakness. It is the most common type of muscular dystrophy. DMD is caused by an absence of dystrophin, a protein that helps keep muscle cells intact. The first symptoms are usually seen between three and five years of age, and worsen over time. The disease often occurs in people without a known family history of the condition and primarily affects boys, but in rare cases it can affect girls. DMD occurs in about one out of every 3,600 male infants worldwide.

People with DMD progressively lose the ability to perform activities independently and often require use of a wheelchair by their early teens. As the disease progresses, life-threatening heart and respiratory conditions can occur. Patients typically succumb to the disease in their 20s or 30s; however, disease severity and life expectancy vary.

Exondys 51 was approved under the accelerated approval pathway, which provides for the approval of drugs that treat serious or life-threatening diseases and generally provide a meaningful advantage over existing treatments. Approval under this pathway can be based on adequate and well-controlled studies showing the drug has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit to patients (how a patient feels or functions or whether they survive). This pathway provides earlier patient access to promising new drugs while the company conducts clinical trials to verify the predicted clinical benefit.

The accelerated approval of Exondys 51 is based on the surrogate endpoint of dystrophin increase in skeletal muscle observed in some Exondys 51-treated patients. The FDA has concluded that the data submitted by the applicant demonstrated an increase in dystrophin production that is reasonably likely to predict clinical benefit in some patients with DMD who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping. A clinical benefit of Exondys 51, including improved motor function, has not been established. In making this decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease for these children and the lack of available therapy.