canakinumab

Novartis drug Ilaris® approved by FDA to treat active systemic juvenile idiopathic arthritis, a serious form of childhood arthritis.

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  • Ilaris® (canakinumab) is the first interleukin-1 beta inhibitor for the treatment of SJIA and the only treatment approved specifically for SJIA that is given as a monthly subcutaneous injection[1]

 

  • In Phase III studies, 84% of Ilaris-treated SJIA patients achieved significant improvement of systemic and arthritic symptoms (pediatric ACR30) after a single subcutaneous dose[1]

 

  • SJIA is a rare, disabling autoinflammatory disease with limited treatment options[2]; Ilaris is being investigated in other inflammatory conditions, including several rare diseases for which approved treatment options do not exist

 

 Novartis announced today that the US Food and Drug Administration (FDA) has approved Ilaris® (canakinumab) for the treatment of active systemic juvenile idiopathic arthritis (SJIA) in patients aged 2 years and older. Ilaris is the first interleukin-1 beta (IL-1 beta) inhibitor approved for SJIAand the only treatment approved specifically for SJIA that is given as a once-monthly subcutaneous injection[1]. SJIA is a rare and disabling form of childhood arthritis characterized by spiking fever, rash and arthritis that can affect children as young as 2 years old and can continue into adulthood[2],[3].

 

This approval was based on two Phase III trials in SJIA patients, aged 2-19, showing significant improvement in the majority of Ilaris-treated patients[1]. Study 1 showed that 84% of patients treated with one subcutaneous dose of Ilaris achieved the primary endpoint of the adapted pediatric American College of Rheumatology 30 (ACR30), compared to 10% achievement of ACR30 for placebo at Day 15[1]. In the open-label part of Study 2, 92 of 128 patients attempted “corticosteroid tapering”. Of those 92 patients, 62% were able to substantially reduce their use of corticosteroids, and 46% completely discontinued corticosteroids[1]. In the controlled portion of Study 2, there was a 64% relative reduction in the risk of flare for patients in the Ilaris group as compared to those in the placebo group (hazard ratio of 0.36; 95% CI: 0.17 to 0.75).

 

“In the US, this approval marks the second Ilaris indication for patients living with rare, autoinflammatory conditions,” said Timothy Wright, MD, Global Head of Development, Novartis Pharmaceuticals. “We are committed to studying Ilaris in other IL-1 beta mediated inflammatory diseases, including several rare diseases for which treatment options do not currently exist.”

 

SJIA affects 5-15 children per 100,000 in the United States,and is the most severe subtype of juvenile idiopathic arthritis[3]-[5]. Although the disease can be life-threatening, treatment options are limited. Corticosteroids are often used to treat symptoms and pain despite their long term use being associated with potentially serious adverse effects, including Cushing syndrome, growth suppression and osteoporosis[1],[6],[7].

 

Ilaris is being investigated in a number of rare autoinflammatory conditions, including Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), colchicine-resistant Familial Mediterranean Fever (FMF) and Hyper IgD Syndrome (HIDS). Ilaris is considered an investigational agent for these conditions at this point in time. As such, the role that Ilaris could play in treating these conditions and potential benefit to patients is still being determined.

 

About the Pivotal Phase III Studies

Study 1, a 4-week, randomized, double-blind, placebo-controlled study, involved 84 patients between the ages of 2 and 19 years with active SJIA[1],[2]. Patients were treated with either a single subcutaneous dose of Ilaris (4 mg/kg, up to 300 mg) (n=43) or placebo (n=41)[1]. The primary endpoint was the proportion of patients achieving the adapted pediatric American College of Rheumatology (ACR) 30 response criteria and resolution of fever from baseline at Day 15[1]. This means that patients had at least a 30% improvement in systemic and arthritic symptoms versus baseline. The study met its primary endpoint.

 

Study 2, a two-part study, had an open-label, single-arm active treatment in Part I followed by a randomized, double-blind, placebo-controlled, event-driven withdrawal design in Part II[1]. A total of 177 patients between the ages of 2 and 19 years with active SJIA were enrolled in the study[1]. Some of these patients had previously participated in the Study 1. In Part I, patients received a subcutaneous dose of Ilaris (4 mg/kg, up to 300 mg) every 4 weeks[1]. The primary endpoint of Part I was to assess whether treatment with Ilaris allowed successful tapering of corticosteroids in at least 25% of SJIA patients who entered the study using a corticosteroid.

 

In Part II of the study, patients were randomized to either continue receiving Ilaris, or to receive placebo every 4 weeks (“placebo-after-Ilaris group”), until a pre-specified number (37) of flare-events (“flares”) had occurred[1]. The primary endpoint of Part II was to demonstrate that the time to flare was longer with Ilaris than with placebo.

 

The primary endpoints for Study 1 and Study 2 were all met.

 

About Ilaris

Ilaris is a selective, fully human, monoclonal antibody that inhibits IL-1 beta, which is an important part of the body’s immune system defenses[1]. Excessive production of IL-1 beta plays a prominent role in certain inflammatory diseases[8]. Ilaris works by neutralizing IL-1 beta for a sustained period of time, therefore inhibiting inflammation[1].

 

In addition to its approval for SJIA in the US, Ilaris is approved in the EU for the treatment of refractory gouty arthritis, and in more than 60 countries, including in the EU, US, Switzerland and Japan for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), a rare, lifelong, genetic disorder with debilitating symptoms[1]. The approved indication may vary depending upon the individual country.

 

References:

  1. Ilaris [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2013.
  2. Woo P. Systemic juvenile idiopathic arthritis: diagnosis, management, and outcome. Nat Clin Pract Rheumatol 2006; 2(1):28-34.
  3. Ramanan AV, Grom AA. Does systemic-onset juvenile idiopathic arthritis belong under juvenile idiopathic arthritis? Rheumatology (Oxford) 2005; 44(11):1350-3.
  4. Beukelman T, Patkar NM, Saag KG, et al. 2011 American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis: Initiation and Safety Monitoring of Therapeutic Agents for the Treatment of Arthritis and Systemic Features. Arthritis Care & Research 2011; 63(4):465-482.
  5. Dewitt EM, Kimura Y, Beukelman T, et al. Consensus Treatment Plans for New-Onset Systemic Juvenile Idiopathic Arthritis. Arthritis Care & Research 2012; 64(7):1001-1010.
  6. U.S. National Library of Medicine (NLM), National Institutes of Health (NIH). Cushing Syndrome. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/000389.htm. Last accessed: 12/12/12.
  7. Teitelbaum SL,Seton MP, Saag KG. Should Bisphosphonates be Used for Long-Term Treatment of Glucocorticoid-Induced Osteoporosis? Arthritis Rheum. 2011 February 63(2): 325-328. doi:10.1002/art.30135.
  8. Martinon F, Petrilli V.  Gout-associated uric acid crystals activate the NALP3 inflammasome.Nature 2006; 440(9): 237-241.

 

Source: Novartis newsletter

Novartis receives EU approval for Ilaris® in patients suffering acute gouty arthritis attacks who cannot gain relief from current treatments .

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  • Ilaris® is the first biologic approved in the EU for symptomatic pain relief in a gouty arthritis indication, and is administered in a single, subcutaneous injection[1] 
  • The intense inflammatory response associated with gouty arthritis attacks can cause severe pain and debilitating symptoms that can last a week or more. 
  • Existing treatments are unsuitable to treat these crippling attacks for certain groups of gouty arthritis patients, particularly those with serious comorbidities[5],[6] 
  • Ilaris, the only approved fully human monoclonal antibody targeting interleukin-1 beta (IL-1 beta), is being investigated in a number of rare inflammatory conditions

Novartis announced today that the European Commission (EC) has approved llaris (canakinumab, ACZ885) in the treatment of patients with acute gouty arthritis who suffer frequent attacks, and whose symptoms cannot or should not be managed with current treatment options. Ilaris is the first biologic approved in the EU for symptomatic pain relief in a gouty arthritis indication, and is administered in a single, subcutaneous injection of 150 mg[1].

Ilaris is specifically indicated for the ‘symptomatic treatment of adult patients with frequent gouty arthritis attacks (at least 3 attacks in the previous 12 months) in whom non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine are contraindicated, are not tolerated, or do not provide an adequate response, and in whom repeated courses of corticosteroids are not appropriate'[1].

The EC also granted an additional year of data exclusivity to Novartis based on the significant clinical benefit over existing treatments demonstrated for Ilaris.

“The approval of Ilaris for acute gouty arthritis attacks in patients without appropriate treatment options provides new hope for those debilitated by this excruciating condition,” said David Epstein, Division Head of Novartis Pharmaceuticals. “Ilaris targets interleukin-1 beta, a key player in gouty arthritis inflammation. Our vision is to realize the potential of Ilaris wherever IL-1 beta plays a key role and available treatment options don’t give patients the help they need.”

Gouty arthritis, commonly referred to as gout, is a serious, chronic and progressive inflammatory disease that generally affects 1 to 4% of adults[2],[7]-[10]. Gouty arthritis attacks occur when the body has a strong inflammatory response to uric acid crystals forming in the affected joint, typically of the toe, foot, ankle, or knee[2],[4]. The disease is associated with a high prevalence of comorbidities, such as hypertension, kidney disease, diabetes, dyslipidemia and cardiovascular disease. These conditions can lead to contraindications for existing therapies and complications for disease management[5],[6],[11],[12].

Data from two Phase III trials and their extensions, which supported the EU approval for Ilaris in acute gouty arthritis attacks, showed that patients treated with Ilaris experienced significantly greater pain relief compared to the injectable steroid triamcinolone acetonide (TA)[13]. The majority of adverse events (AEs) were mild to moderate, with infections (e.g. upper respiratory tract infections and nasopharyngitis) being the most frequent of them.

About Ilaris Phase III Studies
Ilaris has been assessed for the treatment of acute gouty arthritis attacks in two multicentre, randomized, double-blind, active-controlled studies in patients with frequent gouty arthritis attacks (>=3 in the previous year) who were unable to use NSAIDs or colchicine (due to contraindication, intolerance or lack of efficacy). The studies were 12 weeks in duration followed by 12 week double-blind initial extensions[13].

A total of 454 patients were randomized to receive a single dose of Ilaris 150 mg via subcutaneous injection or TA 40 mg via intramuscular injection[13].

Both trials used an internationally recognized pain scale (visual analogue scale, or VAS) to measure differences in pain 72 hours after treatment. Pain intensity in the overall study population was statistically significantly lower for Ilaris 150 mg compared to TA at 72 hours (-10.7 mm, p<0.0001), with an absolute mean decrease in VAS score of approximately -50 mm. Reduction in pain was observed as early as 6 hours after dosing in both groups. A statistically significant difference between treatments was observed from 24 hours to 7 days. Ilaris also reduced the risk of subsequent attacks[13].

Safety results showed an increased incidence of AEs for Ilaris compared to TA, with 66% vs. 53% of patients reporting any adverse event and 20% vs. 10% of patients reporting an infection adverse event over 24 weeks[1].

A sub-analysis of these studies included 101 patients unable to use NSAIDs and colchicine, and on stable urate lowering therapy (ULT) or unable to use ULT. Pain relief was similar to that shown in the total study population (-10.2 mm for Ilaris 150 mg compared with TA at 72 hours, p=0.0208)[14].

About Ilaris
Ilaris is a selective, fully human, monoclonal antibody that inhibits IL-1 beta, which is an important part of the body’s immune system defenses[1]. Excessive production of IL-1 beta plays a prominent role in certain inflammatory diseases. Ilaris works by neutralizing IL-1 beta for a sustained period of time, therefore inhibiting inflammation.

In addition to its approval in refractory gouty arthritis in the EU, Ilaris is approved in more than 60 countries, including in the EU, US, Switzerland and Japan for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS). CAPS is a suite of rare, life-long, genetic, autoinflammatory diseases with debilitating symptoms[1]. The approved indication may vary depending upon the individual country.

Ilaris is being investigated in a number of rare inflammatory conditions, which include, systemic juvenile idiopathic arthritis (SJIA), Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), colchicine-resistant Familial Mediterranean Fever (FMF) and cardiovascular disease. Not all patients with these diseases would be eligible for treatment with Ilaris, if approved for the applicable disease.

In the US, Novartis continues to work with the Food and Drug Administration (FDA) to determine the next steps for ACZ885 in gouty arthritis, following a Complete Response letter received in August 2011 with a request by the Agency for additional clinical data to evaluate the benefit risk profile in refractory patients.

About Gouty Arthritis
Gouty arthritis is the most common form of inflammatory arthritis in adults[10],[15]. This chronic and progressive disease is characterized by recurrent attacks in select joints[2]. The intense inflammatory response associated with these attacks may cause severe pain and debilitating symptoms that can last a week or more.

Treatments currently available to manage the pain and inflammation of gouty arthritis attacks, such as NSAIDs, colchicine or corticosteroids, may be inadequate or inappropriate in patients who have certain coexisting medical problems. As a result, there is a significant unmet medical need among individuals with gouty arthritis.

Source: Novartis newsletter.