At this time, the phase III DEFINE trial (CD-003) in Crohn's disease
will not be initiated.
"We thank the patients and the investigators involved in the REVOLVE
Celgene Inflammatory Bowel Disease Portfolio of Novel Medicines Advances
Ozanimod: At the
OTEZLA®: A randomized, controlled, phase II trial (UC-001) in UC is ongoing with data expected by year-end 2017. Pending positive results, a broad phase III UC program could initiate in 2018.
About GED-0301 (mongersen)
The investigational oral antisense therapy GED-0301 (mongersen) is an oligonucleotide that decreases Smad7 protein, thereby potentially impacting TGF-β1 signaling. In patients with Crohn's disease, abnormally high levels of Smad7 interfere with TGF-β1 anti-inflammatory pathways in the gut, leading to increased inflammation.
GED-0301 is an investigational compound that is not approved for any use in any country.
Ozanimod is a novel, oral, selective, sphingosine 1-phosphate 1 (S1PR1) and 5 (S1PR5) receptor modulator in development for immune-inflammatory indications including relapsing multiple sclerosis, ulcerative colitis and Crohn's disease. Selective binding with S1PR1 is believed to inhibit a specific sub set of activated lymphocytes from migrating to sites of inflammation. The result is a reduction of circulating T and B lymphocytes that leads to anti-inflammatory activity. Importantly, immune surveillance is maintained.
Selective binding with S1PR5 is thought to activate specific cells within the CNS. This has the potential to enhance remyelination and prevent synaptic defects. Ultimately, neurological damage may be prevented.
Ozanimod is an investigational compound that is not approved for any use in any country.
OTEZLA® (apremilast) 30 mg tablets is an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP). PDE4 inhibition results in increased intracellular cAMP levels which is thought to indirectly modulate the production of inflammatory mediators. The specific mechanism(s) by which OTEZLA® exerts its therapeutic action in patients with psoriasis or psoriatic arthritis is not well defined.
OTEZLA® (apremilast) is indicated for the treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.
OTEZLA® is indicated for the treatment of adult patients with active psoriatic arthritis.
IMPORTANT SAFETY INFORMATION
OTEZLA® (apremilast) is contraindicated in patients with a known hypersensitivity to apremilast or to any of the excipients in the formulation.
Warnings and Precautions
Diarrhea, Nausea and Vomiting: Cases of severe diarrhea, nausea, and vomiting were associated with the use of OTEZLA®. Most events occurred within the first few weeks of treatment. In some cases, patients were hospitalized. Patients 65 years of age or older and patients taking medications that can lead to volume depletion or hypotension may be at a higher risk of complications from severe diarrhea, nausea, or vomiting. Monitor patients who are more susceptible to complications of diarrhea or vomiting; advise patients to contact their healthcare provider. Consider OTEZLA® dose reduction or suspension if patients develop severe diarrhea, nausea, or vomiting.
Depression: Carefully weigh the risks and benefits of treatment with OTEZLA® for patients with a history of depression and/or suicidal thoughts/behavior, or in patients who develop such symptoms while on OTEZLA®. Patients, caregivers, and families should be advised of the need to be alert for the emergence or worsening of depression, suicidal thoughts or other mood changes, and they should contact their healthcare provider if such changes occur.
Psoriasis: Treatment with OTEZLA® is associated with an increase in depression. During clinical trials, 1.3% (12/920) of patients reported depression compared to 0.4% (2/506) on placebo; Depression was reported as serious in 0.1% (1/1308) of patients exposed to OTEZLA®, compared to none in placebo-treated patients (0/506). Suicidal behavior was observed in 0.1% (1/1308) of patients on OTEZLA®, compared to 0.2% (1/506) on placebo. One patient treated with OTEZLA® attempted suicide; one patient on placebo committed suicide.
Psoriatic Arthritis: Treatment with OTEZLA® is associated with an increase in depression. During clinical trials, 1.0% (10/998) reported depression or depressed mood compared to 0.8% (4/495) treated with placebo. Suicidal ideation and behavior was observed in 0.2% (3/1441) of patients on OTEZLA®, compared to none in placebo treated patients. Depression was reported as serious in 0.2% (3/1441) of patients exposed to OTEZLA®, compared to none in placebo treated patients (0/495). Two patients who received placebo committed suicide compared to none on OTEZLA®.
Weight Decrease: Monitor body weight regularly; evaluate unexplained or clinically significant weight loss, and consider discontinuation of OTEZLA®.
Psoriasis: Body weight loss of 5-10% occurred in 12% (96/784) of patients treated with OTEZLA® and in 5% (19/382) of patients treated with placebo. Body weight loss of ≥10% occurred in 2% (16/784) of patients treated with OTEZLA® compared to 1% (3/382) of patients treated with placebo.
Psoriatic Arthritis: Body weight loss of 5-10% was reported in 10% of patients taking OTEZLA® and in 3.3% of patients taking placebo.
Drug Interactions: Apremilast exposure was decreased when OTEZLA®
was co-administered with rifampin, a strong
Psoriasis: Adverse reactions reported in ≥5% of patients were (OTEZLA®%, placebo%): diarrhea (17, 6), nausea (17, 7), upper respiratory tract infection (9, 6), tension headache (8, 4), and headache (6, 4).
Psoriatic Arthritis: Adverse reactions reported in at least 2% of patients taking OTEZLA®, that occurred at a frequency at least 1% higher than that observed in patients taking placebo, for up to 16 weeks (after the initial 5-day titration), were (OTEZLA®%, placebo%): diarrhea (7.7, 1.6); nausea (8.9, 3.1); headache (5.9, 2.2); upper respiratory tract infection (3.9, 1.8); vomiting (3.2, 0.4); nasopharyngitis (2.6, 1.6); upper abdominal pain (2.0, 0.2).
Use in Specific Populations
Pregnancy and Nursing Mothers: OTEZLA® is Pregnancy Category C; it has not been studied in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether apremilast or its metabolites are present in human milk. Caution should be exercised when OTEZLA® is administered to a nursing woman.
Renal Impairment: OTEZLA® dosage should be reduced in patients with severe renal impairment (creatinine clearance less than 30 mL/min); for details, see Dosage and Administration, Section 2, in the Full Prescribing Information.
Please click here for Full Prescribing Information
This press release contains forward-looking statements, which are
generally statements that are not historical facts. Forward-looking
statements can be identified by the words "expects," "anticipates,"
"believes," "intends," "estimates," "plans," "will," "outlook" and
similar expressions. Forward-looking statements are based on
management's current plans, estimates, assumptions and projections, and
speak only as of the date they are made. We undertake no obligation to
update any forward-looking statement in light of new information or
future events, except as otherwise required by law. Forward-looking
statements involve inherent risks and uncertainties, most of which are
difficult to predict and are generally beyond our control. Actual
results or outcomes may differ materially from those implied by the
forward-looking statements as a result of the impact of a number of
factors, many of which are discussed in more detail in our Annual Report
on Form 10-K and our other reports filed with the
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Patrick E. Flanigan III, 908-673-9969
Corporate Vice President, Investor Relations
Senior Director, Corporate Communications
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