- A range of therapeutics will be evaluated for their potential efficacy and safety relative to the condition severity of patients hospitalized with COVID-19

- Trial sites are being established in hospitals around the world to support enrollment in communities where the virus is present

- This is the first time that industry has come together to launch an adaptive clinical trial

THOUSAND OAKS, Calif., Nov. 30, 2020 /PRNewswire/ -- Three members of the COVID R&D Alliance - Amgen Inc. (NASDAQ: AMGN), Takeda Pharmaceutical Co. Ltd. (NYSE: TAK), and UCB (Euronext BR: UCB) - today announced the first patient enrolled in the COMMUNITY Trial (COVID-19 Multiple Agents and Modulators Unified Industry Members). COMMUNITY is a randomized, double-blind, placebo-controlled, adaptive platform trial that enables an array of therapeutic candidates to be studied in hospitalized COVID-19 patients.

With worldwide COVID-19 deaths exceeding one million and a resurgence of cases globally, life science companies are working urgently to identify treatments that can potentially reduce clinical severity of COVID-19 in hospitalized patients. COMMUNITY is the first platform trial designed and launched by members of the COVID R&D Alliance, a group of more than 20 leading pharmaceutical and biotech companies who are devoting significant time, insights and company resources to speed the development of potential therapies, novel antibodies, and anti-viral therapies for COVID-19 and its related symptoms.

"As this insidious virus rapidly spreads around the globe, doctors need options to treat hospitalized patients who are actively sick and experiencing a range of symptoms as the disease progresses," said David M. Reese, M.D., Executive Vice President Research & Development, Amgen. "Working hand-in-hand with our peers, we hope to find options that could potentially save lives of the patients who will need treatments for COVID-19 before widespread availability of a vaccine."

COMMUNITY uses an adaptive design which allows for the addition, removal and simultaneous study of multiple therapeutic candidates during the course of the trial. Multiple candidates will be tested against a shared placebo-controlled arm. The design allows for a streamlined approach which may accelerate execution of the study and save time as we search for therapeutics in the fight against the pandemic. Immunomodulating therapies will be the first candidates to enter COMMUNITY. Other therapies may join in the future, such as antivirals.

The trial's design and global footprint were selected to address potential barriers in the study of COVID-19 therapeutics. This includes anticipating and activating trial sites to align with the rise and fall of COVID cases across geographic regions as well as streamlining an influx in trial-related inquiries faced by some hospitals and health systems. COMMUNITY will onboard global sites in the United States, Brazil, Mexico, Russia, South Africa and other countries.  This geographic diversity will allow the trial sites to be active when cases spike locally. COMMUNITY aims to simplify the study of investigational therapies that may result in potential treatment options and address the needs of hospitals in treating patients.

"COVID is not confined to one country, making it imperative that we share the challenges, successes and insights in real-time," said Dhavalkumar Patel, Executive Vice President and Chief Scientific Officer, UCB. "By sharing our expertise and resources, we hope to arm care teams with promising investigational therapies to help patients who cannot wait."

Uncontrolled vascular and immune inflammatory responses have proven to be hallmark symptoms in patients facing severe COVID-19 infections. These patients may face increased risk of acute respiratory distress syndrome (ARDS), stroke and death. Initial therapies entering into COMMUNITY were selected based upon their potential to suppress or control the immune response or the resulting inflammation. None of these therapies have been approved by the FDA, EMA, or other health authorities for the treatment of COVID-19 or its symptoms and are still investigational. These include:

• Amgen's OTEZLA® (apremilast), which may suppress immune response inflammation;
• Takeda's investigational intravenous administration of lanadelumab, which modulates the kallikrein-kinin system and suppresses production of bradykinin, potentially lessening inflammation;
• UCB's zilucoplan, an investigational medicine that may reduce overactivation of the immune system that contributes to ARDS.

OTEZLA entered COMMUNITY this week. It is expected lanadelumab and zilucoplan will enter in the coming weeks. Other anti-viral, immunomodulating and vascular agents may enter in the coming months.

COMMUNITY is studying hospitalized COVID-19 patients. This includes confirmed COVID-19 patients who may require either ongoing medical care, supplemental oxygen, noninvasive ventilation or high-flow oxygen devices, or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO). By enrolling both hospitalized Intensive Care Unit and non-Intensive Care Unit patients, the trial seeks to yield greater understanding of how therapeutic interventions may be used with hospitalized COVID-19 patients experiencing a range of symptoms.

About COMMUNITYCOMMUNITY is an adaptive, randomized, double-blind, placebo-controlled platform study designed to assess multiple candidates as a potential treatment for hospitalized patients with COVID-19, a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV 2). The focus of the trial is to identify an effective treatment(s) for hospitalized COVID-19 patients, who are Grade 2 to Grade 5 on a Clinical Severity Status 8-Point Ordinal Scale.

The primary endpoint of COMMUNITY is time to confirmed clinical recovery without being re-hospitalized through Day 29 based on the clinical severity status scale, which is defined as achieving a score of 6, 7, or 8. Key secondary endpoints are oxygen-free recovery, improvement from baseline or fit for discharge from baseline, and all-cause mortality.

Patients will be randomized equally to either the candidate agent plus the standard of care or a placebo plus standard of care in a double-blind fashion. Patients who are randomized to placebo plus standard of care will be subsequently randomized equally to a matching placebo corresponding to an available agent.

About the COVID R&D AllianceOrganized in March 2020, the COVID R&D Alliance is operating unconstrained by past models of development and is accelerating the study candidates without regard to company affiliation. Members are sharing clinical trial data and real-world evidence, as well as crowd-sourcing early stage candidates to identify mechanisms and treatments that may be effective against COVID-19. Initial efforts by the group focus on advancing well understood therapies and late-stage investigational medicines for hospitalized patients who need treatment options. Activities are testing re-purposed molecules and early stage candidates. Member companies have 40 trials expected to have findings in the coming months.

Additional information on the COVID R&D Alliance is available at www.CovidRDAlliance.com.

About Otezla® (apremilast)OTEZLA® (apremilast) 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 is not well defined.

Otezla is currently approved for use in more than 50 countries as an oral treatment for inflammatory diseases such as psoriasis and psoriatic arthritis. By inhibiting PDE4, Otezla is thought to modulate the production of inflammatory cytokines and other mediators, which may prove helpful in inhibiting the inflammatory response associated with the signs, symptoms and pulmonary involvements observed in some COVID-19 patients. Amgen plans to collaborate with platform trials to investigate Otezla in treatment of hospitalized COVID-19 patients.

Otezla® (apremilast) U.S. INDICATIONSOtezla® (apremilast) is indicated for the treatment of adult 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.

Otezla is indicated for the treatment of adult patients with oral ulcers associated with Behçet's Disease.

Otezla® (apremilast) U.S. IMPORTANT SAFETY INFORMATION

Contraindications

• 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
• Behçet's Disease: Treatment with Otezla is associated with an increase in depression. During the phase 3 clinical trial, 1% (1/104) reported depression or depressed mood compared to 1% (1/103) treated with placebo. No instances of suicidal ideation or behavior were reported in patients treated with Otezla or treated with placebo

• Weight Decrease: Monitor body weight regularly; evaluate unexplained or clinically significant weight loss, and consider discontinuation of Otezla
• Psoriasis: During clinical trials, 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: During clinical trials, body weight loss of 5-10% was reported in 10% (49/497) of patients taking Otezla and in 3.3% (16/495) of patients taking placebo
• Behçet's Disease: During the phase 3 clinical trial, body weight loss of >5% was reported in 4.9% (5/103) of patients taking Otezla and in 3.9% (4/102) of patients taking placebo

• Drug Interactions: Apremilast exposure was decreased when Otezla was co-administered with rifampin, a strong CYP450 enzyme inducer; loss of Otezla efficacy may occur. Concomitant use of Otezla with CYP450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin) is not recommended

Adverse Reactions

• 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)
• Behçet's Disease: Adverse reactions reported in at least ≥5% of patients taking Otezla, that occurred at a frequency at least 1% higher than that observed in patients taking placebo, for up to 12 weeks, were (Otezla%, placebo%): diarrhea (41.3, 20.4); nausea (19.2, 10.7); headache (14.4, 10.7); upper respiratory tract infection (11.5, 4.9); upper abdominal pain (8.7, 1.9); vomiting (8.7, 1.9); back pain (7.7, 5.8); viral upper respiratory tract infection (6.7, 4.9); arthralgia (5.8, 2.9)

Use in Specific Populations

• Pregnancy: Otezla has not been studied in pregnant women. Advise pregnant women of the potential risk of fetal loss. Consider pregnancy planning and prevention for females of reproductive potential. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Otezla during pregnancy. Information about the registry can be obtained by calling 1-877-311-8972 or visiting https://mothertobaby.org/ongoing-study/otezla/
• Lactation: There are no data on the presence of apremilast or its metabolites in human milk, the effects of apremilast on the breastfed infant, or the effects of the drug on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Otezla and any potential adverse effects on the breastfed child from Otezla or from the underlying maternal condition
• 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 Otezla® Full Prescribing Information.

About lanadelumab

Lanadelumab is a fully human monoclonal antibody that specifically binds and inhibits plasma kallikrein activity. Lanadelumab is produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology.

Based on its mechanism of action, lanadelumab may prevent the pro-inflammatory effects of SARS-COV2 and the extravasation and accumulation of fluid within the lungs during a serious and prolonged COVID-19 illness by decreasing plasma kallikrein activity and regulating excess bradykinin signaling. In addition, lanadelumab-induced plasma kallikrein inhibition may help to reduce inflammation and coagulation driven by FXII, which is activated by plasma kallikrein through a positive feedback loop. An investigational intravenous administration of lanadelumab is being studied.

Lanadelumab (marketed under the tradename TAKHZYRO®) is approved as a subcutaneous formulation for prophylaxis to prevent attacks of hereditary angioedema (HAE) in patients ≥12 years of age.

U.S. INDICATION AND IMPORTANT SAFETY INFORMATION INDICATION TAKHZYRO (lanadelumab-flyo) is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in patients ≥12 years of age.

IMPORTANT SAFETY INFORMATION Hypersensitivity reactions have been observed. In case of a severe hypersensitivity reaction, discontinue TAKHZYRO administration and institute appropriate treatment.

Adverse Reactions: The most commonly observed adverse reactions (≥10% and higher than placebo) associated with TAKHZYRO were injection site reactions consisting mainly of pain, erythema, and bruising at the injection site; upper respiratory infection; headache; rash; myalgia; dizziness; and diarrhea. Less common adverse reactions observed included elevated levels of transaminases; one patient discontinued the trial for elevated transaminases.

Use in Specific Populations: The safety and efficacy of TAKHZYRO in pediatric patients