FDA Approves Amgen's AVSOLA™ (infliximab-axxq), For The Same Indications As Remicade® (infliximab)

Amgen's Fourth FDA Approval From Biosimilars Portfolio

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Dec 06, 2019, 14:31 ET

THOUSAND OAKS, Calif., Dec. 6, 2019 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced that the U.S. Food and Drug Administration (FDA) has approved AVSOLA™ (infliximab-axxq) for all approved indications of the reference product, Remicade^® (infliximab): for the treatment of moderate-to-severe rheumatoid arthritis (RA), moderate-to-severe Crohn's Disease (CD) in the adult and pediatric population, moderate-to-severe ulcerative colitis (UC) in the adult and pediatric population, chronic severe plaque psoriasis (PsO), psoriatic arthritis (PsA) and ankylosing spondylitis (AS).

"The approval of AVSOLA represents an important milestone across our biosimilar and inflammation portfolios," said Murdo Gordon, executive vice president of Global Commercial Operations at Amgen. "Following July's exciting launches of our two biosimilars in oncology, AVSOLA highlights Amgen's long-term commitment to providing more affordable biological treatment options to patients across critical disease states, including chronic inflammatory conditions."

AVSOLA, an anti-tumor necrosis factor alpha (anti-TNF) monoclonal antibody, was proven to be highly similar to Remicade with no clinically meaningful differences based on a totality of evidence which included comparative analytical, nonclinical and clinical data. The data package was composed of, in part, results from a pharmacokinetic (PK) similarity study conducted in healthy subjects, and a comparative clinical study conducted in patients with moderate to severe RA.

The randomized, double-blind comparative clinical study evaluated the efficacy and safety of AVSOLA compared to Remicade in patients with moderate-to-severe RA. There were 558 patients enrolled and randomized (1:1) to receive either AVSOLA or Remicade at a dose of 3 mg/kg administered as an infusion on day 1, at weeks 2 and 6, and every 8 weeks thereafter. The primary endpoint was the response difference (RD) of 20% improvement in American College of Rheumatology core set measurements (ACR20) at week 22. Key secondary endpoints included DAS28-CRP change from baseline, RD of ACR20, ACR50 and ACR70 at weeks 2, 6, 14, 22, 30, 34, 38, 46 and 50. The study also incorporated the evaluation of a single transition in 119 subjects from Remicade to AVSOLA at week 22, which demonstrated similar safety and immunogenicity in patients who were previously on Remicade.

Amgen has a total of 10 biosimilars in its portfolio, four of which have been approved in the U.S., and 3 that are approved in the European Union (EU).

About AVSOLA™ (infliximab-axxq) in the U.S.
AVSOLA is a biosimilar to Remicade, an anti-tumor necrosis factor alpha (anti-TNF) monoclonal antibody. The active ingredient of AVSOLA is an anti-TNF monoclonal antibody that has the same amino acid sequence as Remicade. AVSOLA also has the same pharmaceutical dosage form and strength as Remicade.

AVSOLA is currently not available commercially. This is not an offer for sale. The following information is derived from the approved label in the U.S.

In the U.S., AVSOLA is approved for:

Rheumatoid Arthritis

AVSOLA, in combination with methotrexate, is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis.

Crohn's Disease

AVSOLA is indicated for

reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy.
reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn's disease.

Pediatric Crohn's Disease

AVSOLA is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy.

Ulcerative Colitis

AVSOLA is indicated for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy.

Pediatric Ulcerative Colitis

AVSOLA is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy.

Plaque Psoriasis

AVSOLA is indicated for the treatment of adult patients with chronic severe (i.e., extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. AVSOLA should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.

Psoriatic Arthritis

AVSOLA is indicated for reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis.

Ankylosing Spondylitis

AVSOLA is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.

AVSOLA™ U.S. Important Safety Information

SERIOUS INFECTIONS

Patients treated with infliximab products are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue AVSOLA if a patient develops a serious infection or sepsis.

Reported infections include:

Active tuberculosis (TB), including reactivation of latent TB. Patients frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before AVSOLA use and during therapy. Treatment for latent infection should be initiated prior to AVSOLA use.
Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, pneumocystosis, and cryptococcosis. Patients may present with disseminated, rather than localized, disease. Empiric antifungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.
Bacterial, viral and other infections due to opportunistic pathogens, including Legionella, Listeria and Salmonella.

The risks and benefits of treatment with AVSOLA™ should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with AVSOLA™, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy, who are on treatment for latent TB, or who were previously treated for TB infection.

Risk of infection may be higher in patients greater than 65 years of age, pediatric patients, patients with co-morbid conditions and/or patients taking concomitant immunosuppressant therapy. In clinical trials, other serious infections observed in patients treated with infliximab products included pneumonia, cellulitis, abscess, and skin ulceration.

MALIGNANCIES

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers, including infliximab products. Approximately half of these cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants.

Postmarketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including infliximab products. These cases have had a very aggressive disease course and have been fatal. The majority of reported cases have occurred in patients with Crohn's disease or ulcerative colitis and most were in adolescent and young adult males. Almost all patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF-blocker at or prior to diagnosis. Carefully assess the risks and benefits of treatment with AVSOLA™, especially in these patient types.

In clinical trials of all TNF inhibitors, more cases of lymphoma were observed compared with controls and the expected rate in the general population. However, patients with Crohn's disease, rheumatoid arthritis, or plaque psoriasis may be at higher risk for developing lymphoma. In clinical trials of some TNF inhibitors, including infliximab products, more cases of other malignancies were observed compared with controls. The rate of these malignancies among patients treated with infliximab products was similar to that expected in the general population, whereas the rate in control patients was lower than expected. Cases of acute and chronic leukemia have been reported with postmarketing TNF-blocker use. As the potential role of TNF inhibitors in the development of malignancies is not known, caution should be exercised when considering treatment of patients with a current or a past history of malignancy or other risk factors such as chronic obstructive pulmonary disease (COPD).

Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-blocker therapy, including infliximab products. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.

A population-based retrospective cohort study found a 2- to 3-fold increase in the incidence of invasive cervical cancer in women with rheumatoid arthritis treated with infliximab compared to biologics-naïve patients or the general population, particularly those over 60 years of age. A causal relationship between infliximab products and cervical cancer cannot be excluded. Periodic screening should continue in women treated with AVSOLA.

CONTRAINDICATIONS

AVSOLA is contraindicated in patients with moderate to severe (NYHA Class III/IV) congestive heart failure (CHF) at doses greater than 5 mg/kg. Higher mortality rates at the 10 mg/kg dose and higher rates of cardiovascular events at the 5 mg/kg dose have been observed in these patients. AVSOLA should be used with caution and only after consideration of other treatment options. Patients should be monitored closely. Discontinue AVSOLA if new or worsening CHF symptoms appear. AVSOLA should not be (re)administered to patients who have experienced a severe hypersensitivity reaction or to patients with hypersensitivity to murine proteins or other components of the product.

HEPATITIS B REACTIVATION

TNF inhibitors, including infliximab products, have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases were fatal. Patients should be tested for HBV infection before initiating AVSOLA. For patients who test positive, consult a physician with expertise in the treatment of hepatitis B. Exercise caution when prescribing AVSOLA for patients identified as carriers of HBV and monitor closely for active HBV infection during and following termination of therapy with AVSOLA. Discontinue AVSOLA in patients who develop HBV reactivation and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of TNF blocker‑ therapy and monitor patients closely.

HEPATOTOXICITY

Severe hepatic reactions, including acute liver failure, jaundice, hepatitis and cholestasis, have been reported in patients receiving infliximab products postmarketing. Some cases were fatal or required liver transplant. Aminotransferase elevations were not noted prior to discovery of liver injury in many cases. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (e.g., ≥5 times the upper limit of normal) develop, AVSOLA should be discontinued, and a thorough investigation of the abnormality should be undertaken.

HEMATOLOGIC REACTIONS

Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia (some fatal) have been reported in patients receiving infliximab products. The causal relationship to infliximab product therapy remains unclear. Exercise caution in patients who have ongoing or a history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs and symptoms of blood dyscrasias or infection. Consider discontinuation of AVSOLA in patients who develop significant hematologic abnormalities.

HYPERSENSITIVITY

Infliximab products have been associated with hypersensitivity reactions that differ in their time of onset. Anaphylaxis, urticaria, dyspnea, and hypotension have occurred in association with infusions of infliximab products. Medications for the treatment of hypersensitivity reactions should be available.

CARDIOVASCULAR AND CEREBROVASCULAR REACTIONS DURING AND AFTER INFUSION

Serious cerebrovascular accidents, myocardial ischemia/infarction (some fatal), hypotension, hypertension, and arrhythmias have been reported during and within 24 hours of initiation of infliximab product infusion. Cases of transient visual loss have been reported during or within 2 hours of infusion of infliximab. Monitor patients during infusion and if a serious reaction occurs, discontinue infusion. Manage reactions according to signs and symptoms.

NEUROLOGIC REACTIONS

Agents that inhibit TNF have been associated with CNS manifestation of systemic vasculitis, seizure and new onset or exacerbation of CNS demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain‑Barré syndrome. Exercise caution when considering AVSOLA in patients with these disorders and consider discontinuation if these disorders develop.

AUTOIMMUNITY

Treatment with infliximab products may result in the formation of autoantibodies and in the development of a lupus‑like syndrome. Discontinue treatment with AVSOLA if symptoms of a lupus-like syndrome develop.

ADVERSE REACTIONS

In clinical trials with infliximab products, the most common adverse reactions occurring in >10% of patients included infections (e.g., upper respiratory, sinusitis, and pharyngitis), infusion-related reactions, headache, and abdominal pain.

USE WITH OTHER DRUGS

Concomitant use of AVSOLA with anakinra, abatacept, tocilizumab, or other biologics used to treat the same conditions as AVSOLA is not recommended because of the possibility of an increased risk of infection. Care should be taken when switching from one biologic to another, since overlapping biological activity may further increase the risk of infection.

LIVE VACCINES/THERAPEUTIC INFECTIOUS AGENTS

Live vaccines or therapeutic infectious agents should not be given with AVSOLA™ due to the possibility of clinical infections, including disseminated infections.

Bring pediatric patients up to date with all vaccinations prior to initiating AVSOLA™. At least a 6-month waiting period following birth is recommended before the administration of any live vaccine to infants exposed in utero to infliximab products.

Please see full Prescribing Information, including Boxed WARNINGS, at www.Amgen.com.

About Amgen Biosimilars
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For more information, visit www.amgenbiosimilars.com and follow us on www.twitter.com/amgenbiosim.

About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.

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