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Coronavirus (COVID-19) Update: FDA Authorizes First Test for Patient At-Home Sample Collection

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Coronavirus (COVID-19) Update: FDA Authorizes First Test for Patient At-Home Sample Collection

April 21, 2020: ‘The U.S. Food and Drug Administration authorized the first diagnostic test with a home collection option for COVID-19. Specifically, the FDA re-issued the emergency use authorization (EUA) for the Laboratory Corporation of America (LabCorp) COVID-19 RT-PCR Test to permit testing of samples self-collected by patients at home using LabCorp’s Pixel by LabCorp COVID-19 Test home collection kit.

“Throughout this pandemic we have been facilitating test development to ensure patients access to accurate diagnostics, which includes supporting the development of reliable and accurate at-home sample collection options,” said FDA Commissioner Stephen M. Hahn, M.D. “The FDA’s around-the-clock work since this outbreak began has resulted in the authorization of more than 50 diagnostic tests and engagement with over 350 test developers. Specifically, for tests that include home sample collection, we worked with LabCorp to ensure the data demonstrated from at-home patient sample collection is as safe and accurate as sample collection at a doctor’s office, hospital or other testing site. With this action, there is now a convenient and reliable option for patient sample collection from the comfort and safety of their home.”

This reissued EUA for LabCorp’s molecular test permits testing of a sample collected from the patient’s nose using a designated self-collection kit that contains nasal swabs and saline. Once patients self-swab to collect their nasal sample, they mail their sample, in an insulated package, to a LabCorp lab for testing.  LabCorp intends to make the Pixel by LabCorp COVID-19 Test home collection kits available to consumers in most states, with a doctor’s order, in the coming weeks.

The LabCorp home self-collection kit includes a specific Q-tip-style cotton swab for patients to use to collect their sample. Due to concerns with sterility and cross-reactivity due to inherent genetic material in cotton swabs, other cotton swabs should not be used with this test at the present time. The FDA continues to work with test developers to determine whether or not Q-tip-style cotton swab can be used safely and effectively with other tests.

This authorization only applies to the LabCorp COVID-19 RT-PCR Test for at-home collection of nasal swab specimens using the Pixel by LabCorp COVID-19 home collection kit. It is important to note that this is not a general authorization for at-home collection of patient samples using other collection swabs, media, or tests, or for tests fully conducted at home.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.”
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-first-test-patient-home-sample-collection

Potential Antiviral Drugs Under Evaluation for the Treatment of COVID-19

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Potential Antiviral Drugs Under Evaluation for the Treatment of COVID-19

Chloroquine or Hydroxychloroquine

Recommendation: There are insufficient clinical data to recommend either for or against using chloroquine or hydroxychloroquine for the treatment of COVID-19 (AIII).

When chloroquine or hydroxychloroquine is used, clinicians should monitor the patient for adverse effects (AEs), especially prolonged QTc interval (AIII).

Rationale for Recommendation: Chloroquine and hydroxychloroquine have been used in small randomized trials and in some case series with conflicting study reports (as described below). Both drugs are available through the Strategic National Stockpile for hospitalized adults and adolescents weighing ≥50 kg who cannot access these drugs through a clinical trial.

Background: Chloroquine is an antimalarial drug developed in 1934. Hydroxychloroquine, an analogue of chloroquine, was developed in 1946 and is used to treat autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In general, hydroxychloroquine has less toxicity (including less propensity to prolong the QTc interval) and fewer drug-drug interactions than chloroquine.

Proposed Mechanism of Action and Rationale for Use in COVID-19:
Both chloroquine and hydroxychloroquine increase the endosomal pH, inhibiting fusion of the SARS-CoV-2 and the host cell membrane.

Chloroquine inhibits glycosylation of the cellular angiotensin-converting enzyme 2 (ACE2) receptor, which may interfere with binding of SARS-CoV to the cell receptor.

In vitro, both drugs may block the transport of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from early endosomes to endolysosomes, which may be required for release of the viral genome.

Several studies have demonstrated in vitro activity of chloroquine against SARS-CoV.

Both drugs have immunomodulatory effects.Clinical Data in COVID-19:

The clinical data available to date on the use of chloroquine and hydroxychloroquine to treat COVID-19 have been mostly from use in patients with mild, and in some cases, moderate disease; data on use of the drugs in patients with severe and critical COVID-19 are very limited. The clinical data are summarized below.

Chloroquine

Study Description: In a small randomized controlled trial in China, 22 hospitalized patients with COVID-19 (none critically ill) were randomized to chloroquine 500 mg orally twice daily or lopinavir 400 mg/ritonavir 100 mg twice daily for 10 days. Patients with a history of heart disease (chronic disease and history of arrhythmia), kidney, liver, or hematologic diseases were excluded from participation. Primary study outcome was SARS-CoV-2 polymerase chain reaction (PCR) negativity at Days 10 and 14. Secondary outcomes included improvement of lung computed tomography (CT) scan at Days 10 and 14, discharge at Day 14, and clinical recovery at Day 10, as well as safety determined by evaluation of study drug-related AEs.

Results: Ten patients received chloroquine and 12 patients received lopinavir/ritonavir. Patients had good peripheral capillary oxygen saturation (SpO2) at baseline (97% to 98%).

Compared to the lopinavir/ritonavir-treated patients, the chloroquine-treated patients had a shorter duration from symptom onset to initiation of treatment (2.5 days vs. 6.5 days, P < 0.001).

Though not statistically significant, patients in the chloroquine arm were younger (median age 41.5 years vs. 53.0 years, P = 0.09). Few patients had co-morbidities.

At Day 10, 90% of the chloroquine-treated patients and 75% of the lopinavir/ritonavir-treated patients had negative SARS-CoV-2 PCR. At Day 14, the percentages for the chloroquine-treated patients and the lopinavir/ritonavir-treated patients were 100% and 91.2%, respectively.

At Day 10, 20% of the chloroquine-treated patients and 8.3% of the lopinavir/ritonavir-treated patients had CT scan improvement. At Day 14, the percentages for the chloroquine-treated patients and lopinavir/ritonavir-treated patients were 100% and 75%, respectively.

At Day 14, 100% of the chloroquine-treated patients and 50% of the lopinavir/ritonavir-treated patients were discharged from the hospital.

The risk ratios of these outcome data cross 1, and the results were not statistically significant.

Both drugs were generally well-tolerated.

Limitations: The trial sample size was very small, and the participants were fairly young.

The chloroquine-treated patients were younger and had fewer symptoms prior to treatment initiation, which are variables that could have affected the study protocol-defined outcomes.

Patients with chronic co-morbidities and critically ill patients were excluded from the study.

Hydroxychloroquine

Study Description: In a randomized controlled trial in China, 62 hospitalized patients with mild (SaO2/SpO2 ratio >93% or PaO2/FIO2 ratio >300 mm Hg) CT-confirmed COVID-19 pneumonia were randomized to hydroxychloroquine 200 twice daily for 5 days plus standard treatment or to standard treatment only.6 Standard treatment included oxygen therapy, antiviral and antibacterial therapy, and immunoglobin, with or without corticosteroids.

Results: Compared to the control patients, the hydroxychloroquine-treated patients had a 1 day-shorter mean duration of fever (2.2 days vs. 3.2 days) and cough (2.0 days vs. 3.1 days).

13% of the control patients and none of the hydroxychloroquine-treated patients experienced progression of illness.

80.6% of hydroxychloroquine-treated patients and 54.8% of control patients experienced either moderate or significant improvement in chest CT scan.

AEs (1 rash, 1 headache) occurred among 2 (6.4%) hydroxychloroquine-treated patients; none occurred among the control patients.

Limitations: The trial had a small sample size and short follow-up.
Standard treatment is complex and not well defined.

The presence and distribution of associated co-morbidities (e.g., hypertension [HTN], diabetes, lung disease) was not reported.

There was no indication that radiologists were blinded to the treatment status of the patients, which could have biased determination of the chest CT outcome.

Study Description: A pilot trial in China randomized 30 patients with COVID-19 to hydroxychloroquine 400 mg once a day for 5 days or conventional treatment.

Results: The trial demonstrated no difference in viral clearance of nasopharyngeal (NP) swabs at Day 7 between the hydroxychloroquine arm (86.7%) and the control arm (93.3%).

One patient in the hydroxychloroquine arm progressed to severe pneumonia. At follow-up, all patients showed clinical improvement.

Study Description: In a case series from France, 26 hospitalized adults with SARS-CoV-2 infection categorized as asymptomatic or with upper or lower respiratory tract infection who received hydroxychloroquine 200 mg 3 times daily for 10 days were compared to 16 control individuals (i.e., who refused treatment, did not meet eligibility criteria, or were from a different clinic).

  • Results: Six patients in the hydroxychloroquine group were excluded from the analysis for the following reasons:
  • One died
  • Three were transferred to the intensive care unit (ICU)
  • One stopped the study drug due to nausea
  • One withdrew from the stud
  • Six patients also received azithromycin.

By Day 6, NP PCRs were negative in 14 of 20 (70%) hydroxychloroquine-treated patients and 2 of 16 (12.5%) controls.

Among the hydroxychloroquine patients, 8 of 14 (57.1%) who received only hydroxychloroquine and 6 of 6 (100%) who received hydroxychloroquine and azithromycin had negative NP PCRs by Day 6.

Clinical outcomes for all patients were not reported.

  • Limitations: There are several methodologic concerns with this case series:
  • The small sample size of the series.
  • The criteria for enrollment of cases and controls is unclear.
  • Asymptomatic individuals were enrolled.
  • Exclusion of six hydroxychloroquine patients includes one death and three ICU transfers.
  • No clinical outcomes were reported; thus, the clinical significance of a negative PCR is unknown.
    The reason for the addition of azithromycin for some patients is unclear.

Adverse Effects:
Chloroquine and hydroxychloroquine have a similar toxicity profile, although hydroxychloroquine is better tolerated and has a lower incidence of toxicity than chloroquine.

Cardiac Adverse Effects: QTc prolongation, Torsade de Pointes, ventricular arrythmia, and cardiac deaths.

The risk of QTc prolongation is greater for chloroquine than for hydroxychloroquine.

Concomitant medications that pose a moderate to high risk for QTc prolongation (e.g., antiarrhythmics, antipsychotics, antifungals, macrolides [including azithromycin] and fluoroquinolone antibiotics)9 should be used only if necessary. Consider using doxycycline rather than azithromycin as empiric therapy for atypical pneumonia.

Baseline and follow-up electrocardiogram (ECG) are recommended when there are potential drug interactions with concomitant medications (e.g., azithromycin) or underlying cardiac diseases.

The risk-benefit ratio should be closely assessed for patients with cardiac disease, history of ventricular arrhythmia, bradycardia (<50 beats per minute), or uncorrected hypokalemia and/or hypomagnesemia.

Other Adverse Effects: Hypoglycemia, rash, and nausea (daily divided doses may reduce nausea). Retinopathy, bone marrow suppression with long-term use, but not likely with short-term use.

There is no evidence that glucose-6-phosphate dehydrogenase (G6PD) deficiency is relevant for the use of hydroxychloroquine, and G6PD testing is not recommended.

With chloroquine use, there is a greater risk for hemolysis in patients with G6PD deficiency. Conduct G6PD testing before initiation of chloroquine. Consider using hydroxychloroquine until G6PD test results are available. If the test results indicate that the patient is G6PD deficient, hydroxychloroquine should be continued.

Drug-Drug Interactions: Chloroquine and hydroxychloroquine are moderate inhibitors of cytochrome P450 (CYP) 2D6 and are also P-glycoprotein (P-gp) inhibitors. Use caution when co-administering the drugs with concomitant medications metabolized by CYP2D6 (e.g., certain antipsychotics, beta-blockers, selective serotonin reuptake inhibitors, and methadone) or transported by P-gp (e.g., certain direct-acting oral anticoagulants or digoxin).

  • Considerations in Pregnancy:
  • Anti-rheumatic doses of chloroquine and hydroxychloroquine have been used safely in pregnant women with SLE.
  • Hydroxychloroquine has not been associated with adverse pregnancy outcomes in ≥300 human pregnancies with exposure to the drug.
  • A lower dose of chloroquine (500 mg once a week) is used for malaria prophylaxis in pregnancy.
  • Dosing/pharmacokinetics/pharmacodynamics: No dosing changes in pregnancy.

Considerations in Children: Chloroquine and hydroxychloroquine have been used routinely in pediatric populations for the treatment and prevention of malaria and for rheumatologic conditions.

Drug Availability: Hydroxychloroquine is Food and Drug Administration (FDA)-approved for the treatment of malaria, lupus erythematosus, and RA and is available commercially. Hydroxychloroquine is not approved for the treatment of COVID-19.

FDA issued an emergency use authorization (EUA) for the use of chloroquine and hydroxychloroquine donated to the Strategic National Stockpile. The EUA authorizes the use of these donated drugs for the treatment of hospitalized adolescent and adult COVID-19 patients who weigh ≥50 kg and for whom a clinical trial is not available, or participation is not feasible.

Hydroxychloroquine plus Azithromycin

Recommendation: The COVID-19 Treatment Guidelines Panel (the Panel) recommends against the use of hydroxychloroquine plus azithromycin for the treatment of COVID-19, except in the context of a clinical trial (AIII).

Rationale for Recommendation: Chloroquine and hydroxychloroquine for COVID-19 have been used in small randomized trials and in some case series with conflicting study reports (as described above). The combination of hydroxychloroquine and azithromycin was associated with QTc prolongation in patients with COVID-19.

Clinical Data in COVID-19

Study Description: In a case series of 80 hospitalized patients with COVID-19 (including six patients from a previous study),8 patients were treated with hydroxychloroquine sulfate 200 mg three times daily for 3 to 10 days plus azithromycin 500 mg for 1 day followed by 250 mg once daily for 4 days. Mean time from symptom onset to treatment was 4.9 ± 3.6 days. Outcomes evaluated included the need for oxygen therapy or ICU transfer after ≥3 days of therapy, NP PCR, SARS-CoV-2 culture, and length of hospitalization.

Clinical Results: One (1.2%) patient died and three (3.8%) patients required ICU transfer, 12 (15%) patients required oxygen therapy.
65 (81.2%) patients were discharged to home or transferred to other units for continuing treatment; 14 (17.4%) patients remained hospitalized at the time the study results were published.

Laboratory Results: 40 of 60 (66.7%) patients tested on Day 6 had negative NP PCR.
All patients tested had negative PCRs by Days 12 through14.
Culture positivity decreased over time among the small number of patients for whom cultures were obtained.

  • Limitations:
  • The trial’s lack of a control group, which is particularly important because many people with mild disease improve in the absence of treatment.
  • The criteria for selection of cases was not reported.
  • Data for PCR and culture results were missing.
  • The definition of “discharge” varied and was unclear.
  • The lack of complete or longer-term follow-up.

Study Description: A prospective case series from France of 11 consecutive hospitalized patients with COVID-19 (eight with significant co-morbid conditions: obesity in two; solid cancer in three; hematological cancer in two; HIV-infection in one). Ten of 11 patients were receiving supplemental oxygen upon treatment initiation.All patients were treated with hydroxychloroquine 600 mg once daily for 10 days and azithromycin 500 mg for 1 day followed by 250 mg once daily for 4 days.

Results: Within 5 days, the condition of three patients worsened, including one patient who died and two patients who were transferred to the ICU.

AEs: Hydroxychloroquine was discontinued in one patient due to QTc prolongation.

Qualitative NP PCR remained positive at Days 5 and 6 after treatment initiation in 8 of 10 patients (repeat testing not done in the patient who died).

Study Description: A case series in the United States reported changes in QTc interval in 84 patients with COVID-19 who received the combination of hydroxychloroquine and azithromycin.

  • Results:
  • 84 patients, 74% male, mean age 63 ± 15 years, 65% had HTN, baseline serum creatinine 1.4 mg/dL, 13% required vasopressors, 11% had coronary artery disease.
  • Concomitant drugs that may prolong QTc interval: 11% on neuropsychiatric drugs and 8% received levofloxacin, lopinavir/ritonavir or tacrolimus.
  • Four patients died, without arrhythmia.
  • Mean baseline QTc was 435 ± 24 ms, mean maximum QTc was 463 ± 35 ms.
  • Mean time to maximum QTc was 3.6 ±1.6 days, ECG follow-up was done for a mean of 4.3 days.
  • 11% of patients developed QTc >500 ms; the QTc increased by 40 to 60 ms and >60 ms in 18% and 12% of patients, respectively.
  • Baseline QTc was not a predictor of subsequent QTc increase during therapy.
  • In multivariate analysis, acute kidney injury (in five patients) was a significant predictor of severe QTc prolongation (odds ratio [OR] 19.45: 95% CI, 2.06–183.88, P = 0.01).

Clinical Trials: Clinical trials to test the safety and efficacy of chloroquine or hydroxychloroquine with or without azithromycin in people who have or are at risk for COVID-19 are in development in the United States and internationally. Please check ClinicalTrials.gov for the latest information.

Lopinavir/Ritonavir and Other HIV Protease Inhibitors

Recommendation: The Panel recommends against the use of lopinavir/ritonavir (AI) or other HIV protease inhibitors (AIII) for the treatment of COVID-19, except in the context of a clinical trial.

Rationale for Recommendation: The pharmacodynamics of HIV protease inhibitors do not support their therapeutic use for COVID-19. Also, lopinavir/ritonavir was studied in a small randomized controlled trial in patients with COVID-19 with negative results (see below).

Lopinavir/Ritonavir

Proposed Mechanism of Action and Rationale for Use in COVID-19:

Replication of SARS-CoV-2 depends on the cleavage of polyproteins into an RNA-dependent RNA polymerase and a helicase. The enzymes responsible for this cleavage are two proteases, 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro).

Lopinavir/ritonavir is an inhibitor of SARS-CoV 3CLpro in vitro, and this protease appears highly conserved in SARS-CoV-2.

Although lopinavir/ritonavir has in vitro activity against SARS-CoV, it is thought to have a poor selectivity index, indicating that higher than tolerable levels of the drug might be required to achieve meaningful inhibition in vivo.

Lopinavir is excreted in the gastrointestinal (GI) tract, and thus coronavirus-infected enterocytes might be exposed to higher concentrations of the drug.

Clinical Data in COVID-19: Study Description: In a Chinese cohort of 55 pre-symptomatic patients identified early in the course of the infection (i.e., tested RT-PCR positive after a family member or close contact was found to have COVID-19), all of whom were given lopinavir/ritonavir for 7 days; all recovered and none required ICU admission.

Study Description: In a clinical trial that randomized 199 patients to lopinavir 400 mg/ritonavir 100 mg orally twice daily for 14 days or to standard of care (SOC), patients randomized to the lopinavir/ritonavir arm did not have a shorter time to clinical improvement.

Results: There was a lower, but not statistically significant, mortality rate (lopinavir/ritonavir 19.2%, on SOC 25.0%) and shorter ICU stay compared to those given SOC (6 days vs. 11 days; difference = -5 days; 95% CI, -9 to 0).

The duration of hospital stays and time to clearance of viral RNA from respiratory tract samples did not differ between the lopinavir/ritonavir and SOC arms.

Nausea, vomiting, and diarrhea were all more frequent in the lopinavir/ritonavir-treated group.

The study was powered only to show a fairly large effect.

Study Description: In a trial of 44 hospitalized patients with mild-to-moderate COVID-19, 21 patients were randomized to lopinavir/ritonavir, 16 patients to the broad-spectrum antiviral Arbidol (available in Russia), and seven patients to SOC.

Results: The time to a negative SARS-CoV-2 nucleic acid pharyngeal swab was not shorter for patients receiving lopinavir/ritonavir (8.5 days [IQR: 3, 13]) than for those receiving SOC (4 days [IQR: 3, 10.5]).

Progression to severe/critical status occurred among eight (38%) patients receiving lopinavir/ritonavir and one patient (14%) on SOC.

Study Description: A small randomized study in China compared lopinavir/ritonavir to chloroquine. Please refer to the chloroquine section for the study description.

Clinical Trials: None in the United States

Monitoring, Adverse Effects, and Drug-Drug Interactions

  • Adverse Effects Include:
  • Nausea, vomiting, diarrhea (common)
  • QTc prolongation
  • Hepatotoxicity

Lopinavir/ritonavir is a potent inhibitor of CYP3A, and many medications metabolized by this enzyme may cause severe toxicity. Please refer to the Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV for a list of potential drug interactions.

Considerations in Pregnancy: There is wide experience with use of lopinavir/ritonavir in pregnant women with HIV and the drug has a good safety profile.

No evidence of human teratogenicity (can rule out a 1.5-fold increase in overall birth defects).

Low placental transfer to the fetus. Please refer to the Recommendations for the Use of Antiretroviral Drugs in Pregnant Women with HIV Infection and Interventions to Reduce Perinatal HIV Transmission in the United States.

Dosing: Lopinavir/ritonavir oral solution contains 42.4% (volume/volume) alcohol and 15.3% (weight/volume) propylene glycol and is not recommended for use during pregnancy. Please refer to the Recommendations for the Use of Antiretroviral Drugs in Pregnant Women with HIV Infection and Interventions to Reduce Perinatal HIV Transmission in the United States.

Once daily lopinavir/ritonavir dosing is not recommended during pregnancy.

Considerations in Children: Lopinavir/ritonavir is approved for the treatment of HIV in infants, children, and adolescents.

There are no data on the efficacy of lopinavir/ritonavir used to treat SARS-CoV-2 infection in pediatric patients.

Darunavir/Cobicistat or Darunavir/Ritonavir

Rationale for Use, Proposed Mechanism of Action for COVID-19:

Inhibition of the 3CLpro enzyme of SARS-CoV-2 and possibly also inhibition of the PLpro enzyme.

Results from an unpublished randomized controlled trial of 30 patients in China showed that darunavir/cobicistat was not effective in the treatment of COVID-19.

Clinical Trials: None in the United States

Other HIV Protease Inhibitors, Including Atazanavir:

There are no data from clinical trials that support the use of other HIV protease inhibitors to treat COVID-19.

Remdesivir

Recommendation: There are insufficient clinical data to recommend either for or against the use of the investigational antiviral agent remdesivir for the treatment of COVID-19 (AIII).

Rationale for Recommendation: Remdesivir is an investigational antiviral drug. Clinical trials of remdesivir for treatment of COVID-19 are underway or in development, but trial data is not yet available.

Proposed Mechanism of Action and Rationale for Use in COVID-19: Remdesivir is an intravenous investigational nucleotide prodrug of an adenosine analog. It has demonstrated in vitro activity against SARS-CoV-2, and in vitro and in vivo activity (based on animal studies) against SARS-CoV and MERS-CoV.Remdesivir binds to the viral RNA-dependent RNA polymerase, inhibiting viral replication through premature termination of RNA transcription.

Preclinical studies show that remdesivir improves disease outcomes and reduces levels of SARS-CoV in mice. When given as prophylaxis or therapy, remdesivir also reduces MERS-CoV levels and lung injury in mice. In a rhesus macaque model of MERS-CoV infection, prophylactic remdesivir prevented MERS-CoV clinical disease. 

When given 12 hours after MERS-CoV infection to rhesus macaques, remdesivir reduced viral replication and the severity of lung disease compared to control animals.

Remdesivir is administered by intravenous infusion at 200 mg on Day 1 followed by 100 mg/day for up to 10 days; the drug is usually infused over 30 to 60 minutes.

Clinical Data to Date: Only anecdotal data are available.

Clinical Trials: Multiple clinical trials are currently underway or in development. Please check ClinicalTrials.gov for the latest information.

In areas of the United States without access to clinical trials, remdesivir may be available through an expanded access program or compassionate use program for a subset of patients.

Monitoring, Adverse Effects, and Drug-Drug Interactions: Remdesivir can cause GI symptoms (e.g., nausea, vomiting), elevated transaminases, and prothrombin time elevation (without change in international normalized ratio [INR]).

Remdesivir is a CYP3A4, CYP2C8, and CYP2D6 substrate in vitro. Coadministration of remdesivir with inhibitors of these enzymes is not expected to have a significant impact on remdesivir concentrations.

Remdesivir concentration may be affected by strong CYP inducers, but the interaction is not expected to be clinically significant.

Because remdesivir formulation contains renally cleared sulfobutylether-beta-cyclodextrin sodium (SBECD), patients with estimated glomerular filtration rate (eGFR) <50 mL/min are excluded from some clinical trials (some trials have a cutoff of eGFR <30 mL/min).

Considerations in Pregnancy: Remdesivir is available for pregnant women through a compassionate access program.

In a randomized controlled Ebola treatment trial of therapies including remdesivir, among 98 females who received remdesivir, six had a positive pregnancy test; the obstetric and neonatal outcomes were not reported in the study.

Considerations in Children: Currently, remdesivir is available for compassionate use for patients aged <18 years.

In the same randomized controlled trial for the treatment of Ebola virus infection, 41 pediatric patients aged <7 days to <18 years received remdesivir. The safety and clinical outcomes in children were not reported separately in the published results for the trial.
https://www.covid19treatmentguidelines.nih.gov/therapeutic-options-under-investigation/antiviral-therapy/

Novartis to sponsor large clinical trial of hydroxychloroquine in hospitalized COVID-19 patients

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Novartis to sponsor large clinical trial of hydroxychloroquine in hospitalized COVID-19 patients

April 20, 2020:  “Novartis has reached an agreement with the US Food and Drug Administration (FDA) to proceed with a Phase III clinical trial with approximately 440 patients to evaluate the use of hydroxychloroquine for the treatment of hospitalized patients with COVID-19 disease.

The clinical trial drug supply will be provided by Sandoz, the generics and biosimilars division of Novartis.

The large trial sponsored by Novartis will be conducted at more than a dozen sites in the United States. Novartis plans to begin enrollment for this study within the next few weeks and is committed to reporting results as soon as possible.

To help achieve broad access to hydroxychloroquine as quickly as possible in these extraordinary circumstances, Novartis will make any intellectual property within our control that relates to the use of hydroxychloroquine to treat or prevent COVID-19 available through non-exclusive voluntary licenses, appropriate waivers, or similar mechanisms.

“We recognize the importance of answering the scientific question of whether hydroxychloroquine will be beneficial for patients with COVID-19 disease,” said John Tsai, Head of Global Drug Development and Chief Medical Officer at Novartis. “We mobilized quickly to address this question in a randomized, double-blind, placebo-controlled study.”

As the new virus continues to spread and claim lives around the globe, doctors and patients are eager for treatment options. In some cases, clinicians are evaluating drugs that have been approved for other diseases, hoping that these will also work against COVID-19.

Patients in the trial will be randomized into three groups. The first group or arm will receive hydroxychloroquine. The second group will receive hydroxychloroquine in combination with azithromycin, which is antibiotic therapy. The third group will receive a placebo. Patients in all treatment groups are receiving standard of care for COVID-19. Researchers at the company compressed months of work into a few weeks to design the large clinical trial in order to rapidly respond to the need for COVID-19 disease treatments.

The clinical trial complements a commitment by Novartis, through Sandoz, to donate up to 130 million tablets of hydroxychloroquine to supply global clinical research efforts in the event the medicine is proven beneficial for the treatment of COVID-19. Sandoz has already donated 30 million tablets to the US Department of Health and Human Services and is dispatching further shipments to countries based on requests from governments around the world.

“We are donating hydroxychloroquine tablets for COVID-19 patients including for use in this and other clinical trials with the hope that researchers and healthcare workers can quickly and scientifically determine whether hydroxychloroquine can help patients around the world combat this disease,” said Richard Saynor, CEO of Sandoz. “We will continue to fulfill orders for existing customers to ensure the medicine remains available to US patients who rely on it for other indicated uses.”

As part of its research and development commitment, Novartis has formed a clinical investigation team to provide rapid access for approved clinical requests and support of clinical evaluation of its medicines to be repurposed and address the needs of patients with COVID-19 infections. In addition to hydroxychloroquine, Novartis plans to sponsor or co-sponsor clinical trials to study ruxolitinib and canakinumab for hospitalized patients with COVID-19 infections. Requests for investigator-initiated trials have been granted for COVID-19-related clinical studies of ruxolitinib, canakinumab, imatinib mesylate, secukinumab, hydroxychloroquine and valsartan.


The drug hydroxychloroquine has garnered interest in the medical community after showing preliminary promise in small clinical studies, including one with co-administration with the antibiotic azithromycin. In addition, hydroxychloroquine has demonstrated antiviral activity against SARS-CoV-2 in laboratory tests. Hydroxychloroquine has long been used for the treatment of malaria and certain autoimmune diseases.” https://www.novartis.com/news/media-releases/novartis-sponsor-large-clinical-trial-hydroxychloroquine-hospitalized-covid-19-patients

UN agencies issue urgent call to fund the global emergency supply system to fight COVID-19

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UN agencies issue urgent call to fund the global emergency supply system to fight COVID-19

April 20, 2020: “The heads of the United Nations’ major agencies have issued a warning of the risk of COVID-19 to the world’s most vulnerable countries. International donors have pledged around a quarter of the US$2 billion the UN requested in the Global Humanitarian Response Plan for COVID-19 in March. 

Following is the text of the open letter: 

 
Dear donor community,

Humanity is collectively facing its most daunting challenge since the Second World War. COVID-19 knows no borders, spares no country or continent, and strikes indiscriminately. By all accounts, we are at least 12 months away from a vaccine.

In this race against an invisible enemy, all countries must fight back, but not all begin from the same starting line. In countries where the world’s most vulnerable need humanitarian aid and supplies to beat back the pandemic, cancelled flights and disrupted supply routes hit disproportionately hard. It is in everyone’s interest to stop the virus from spreading unchecked, destroying lives and economies, and continuing to circle around the world.

The UN Secretary-General on 25 March launched the COVID-19 Global Humanitarian Response Plan, requesting US$2 billion to boost the global response. You have been fast and generous in your funding and have extended lifelines to those who were already caught up in war, poverty and the worst effects of climate change – especially at a time when your own populations are suffering from the impact of the virus.

Around $550 million has generously been made available to implement the Plan so far, with significant additional resources being mobilized and pledged.

The Central Emergency Response Fund (CERF) has also released $95 million to kick-start the COVID-19 response, help contain the spread of the virus, maintain supply chains, and provide assistance and protection to the most vulnerable people, including women and girls, refugees and internally displaced persons. But more needs to be done.

To get more deliveries off the ground, the UN World Food Programme (WFP) is setting up the vital logistics backbone that will help save lives and help halt the spread of the virus. WFP now urgently needs additional funding to establish the necessary transport hubs, charter vessels and provide aircraft for cargo, health workers and other essential staff.

All elements of the Global Humanitarian Response Plan are crucial and need continued funding, but without these logistics common services, the global response could stutter to a halt. Now is not the time to slow down. No one is safe until everyone is safe.

We, humanitarian organizations from across the world, therefore, call upon you to urgently support this global emergency supply system with an initial $350 million to enable a rapid scale-up of logistics common services.

These services, which WFP provides on behalf of the entire global humanitarian community, will enable a swift, efficient response to COVID-19 for the most vulnerable people. Any delay in our action could undermine global efforts to bring the pandemic under control.

The scale-up of the COVID-19 services includes:

              • Establishing, equipping and managing international consolidation hubs and regional staging areas.

              • Air and shipping cargo services.

              • Passenger air services, with the necessary measures to avoid further spreading of the virus.

              • Medical evacuation services for front-line workers.

              • Infrastructure and construction of treatment centres.

              • Real-time remote data collection.

              • Critical investments required to safely deliver operations and services.

Whatever it takes, we as humanitarians are determined to meet people’s urgent needs. The upscaling of the common services that we all depend on is crucial to enable us to meet these needs.

Every human being, in every nation around the world, is facing the same mortal threat. Every step that speeds delivery, saves lives. The COVID-19 pandemic has presented all of humanity with a unique challenge, and only a uniquely global response can halt its forward march.

Now is the time to step up together, to prevent needless suffering, and to fulfil the promise of a better future for all.

We hope to hear from you soon.

Mr. Mark Lowcock, Emergency Relief Coordinator and Under-Secretary-General for Humanitarian Affairs, Office for the Coordination of Humanitarian Affairs (OCHA)

Mr. Filippo Grandi, United Nations High Commissioner for Refugees, United Nations Refugee Agency (UNHCR)

Ms. Henrietta H. Fore, Executive Director, United Nations Children’s Fund (UNICEF)

Mr. David Beasley, Executive Director, United Nations World Food Programme (WFP)

Mr. Achim Steiner, Administrator, United Nations Development Programme (UNDP)

Dr. Tedros Adhanom Ghebreyesus, Director-General, United Nations World Health Organization (WHO)

Mr. Qu Dongyu, Director-General, United Nations Food and Agriculture Organization (FAO)

Mr. António Vitorino, Director-General, United Nations International Organization for Migration (IOM)

Dr. Natalia Kanem, Executive Director, United Nations Population Fund (UNFPA)

Ms. Michelle Bachelet, High Commissioner, United Nations Office of the High Commissioner for Human Rights (OHCHR)

Mr. Gareth Price-Jones, Executive Secretary, Steering Committee for Humanitarian Response (SCHR)

Mr. Ignacio Packer, Executive Director, International Council of Voluntary Agencies (ICVA)

Mr. Sam Worthington, President and CEO, InterAction

Ms. Cecilia Jimenez-Damary, Special Rapporteur on the human rights of internally displaced persons, United Nations Office of the High Commissioner for Human Rights (OHCHR)

Mr. Jagan Chapagain, Secretary General, International Federation of Red Cross and Red Crescent Societies (IFRC)”
https://www.who.int/news-room/detail/20-04-2020-un-agencies-issue-urgent-call-to-fund-the-global-emergency-supply-system-to-fight-covid-19

New study to explore the effects of social distancing launched online

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New study to explore the effects of social distancing launched online

April 21, 2020: Researchers at the University of Oxford are looking for volunteers from across the globe to take part in a new study looking into how social distancing has affected their lives during the Covid-19 pandemic. Volunteers can complete the online survey, which will track people’s feelings and experiences over a 3-month period.

The study is being conducted by an international group of researchers led by Dr. Bahar Tuncgenc, from the University of Nottingham’s School of Psychology and the Social Body Lab at the University of Oxford. ‘

Keeping distance from our loved ones, especially in such uncertain and threatening times, is an unusual and at times difficult way to be asked to live. We want to find out how these distancing measures have been affecting people’s daily lives and what they may have been doing to help get through it,’ says Dr. Tuncgenc.

The study aims to understand what motivates people to adhere to the practice of distancing and how it affects people’s social interactions and mood. The researchers are targeting a wide range of countries including Australia, Bangladesh, China, France, Germany, India, Iran, Italy, Lebanon, Spain, Sweden, Turkey, UK, and USA.

‘Massive cooperation is required to tackle coronavirus,’ says Dr Martha Newson, researcher on the study from the School of Anthropology, University of Oxford. ‘Human beings are an incredibly social species. The effects of isolation could lead to severe, lasting effects on wellbeing and mental health. In tandem with medical research, we need strong research into how the pandemic is affecting our wellbeing.’

Professor Ophelia Deroy, from the Munich Center for Neuroscience at the Ludwig Maximilian University, in Germany says, ‘Politicians have widely called upon individual civic virtue when asking people to observe social distancing. Our study goes beyond the individual scale: we also want to see how people get influenced by others around them. For example, if I think others are lenient on social distancing policies, am I more likely to be lenient as well?’ Answers to these types of questions could provide valuable information for policymakers.” 

Dr. Tuncgenc continues, ‘By targetting over a dozen countries, we will have a unique opportunity to look at how cultural values play a role in people’s experiences. Ultimately, our goal is to help make effective policies, and for that, you need to understand people’s social, psychological and cultural needs.’

To take part in the study, visit https://distancing-covid19-survey.herokuapp.com/  https://www.research.ox.ac.uk/Article/2020-04-21-new-study-to-explore-the-effects-of-social-distancing-launched-online

Five Oxford COVID-19 projects receive UKRI funding

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Five Oxford COVID-19 projects receive UKRI funding

April 20,2020: “Five projects from across Oxford University’s Medical Sciences Division are amongst twenty-one new studies into the novel coronavirus which have been funded by the UK government.

Twenty-one new studies into the novel coronavirus have been funded by the UK government, including the first clinical drug trial in primary care, vaccine and therapy development, and studying epidemiology, disease transmission, behavioral interventions and policy approaches to COVID-19.

This second round of projects receive £14.1 million as part of the £24.6 million rapid research response funded by UK Research and Innovation (UKRI), and by the Department of Health and Social Care through the National Institute for Health Research (NIHR).

These projects build on the UK’s world-class expertise and capability in global heath and infectious disease that has already shaped our understanding of the pandemic and is informing measures to tackle it. They support the UK government’s efforts to save lives, protect the vulnerable and support the NHS so it can help those who need it the most.

UK Research and Innovation Chief Executive, Professor Sir Mark Walport said: ‘The research community’s response to the Covid-19 crisis has been outstanding. In a matter of weeks, researchers have formed projects to develop potential vaccines, repurpose existing drugs and explore the potential for new medicines, and to examine how the virus is transmitted and causes wide variation in symptoms. Pre-clinical trials of vaccines and clinical trials of drugs are already underway.

‘The pace at which this work has been carried out is tribute to the UK’s world-class research base and its dedication to the fight against this disease.’
The projects will run over a maximum 18-month period, ensuring timely insights into the current epidemic.

This research funding has been coordinated with other funders and the World Health Organization (WHO) to ensure there is not duplication of effort and expertise is applied strategically.

On 30 March, UKRI and NIHR launched a joint rolling call for researchers to apply for funding for short-term projects addressing and mitigating the health, social, economic, cultural and environmental impacts of the COVID-19 outbreak.

Oxford’s Medical Sciences Division research projects funded:
Professor Christopher Butler, Nuffield Department of Primary Care Health Sciences, £1.7 million: The first clinical trial in COVID-19 patients consulting in primary care, ‘PRINCIPLE’, will initially test if the anti-malarial drug hydroxychloroquine can reduce the need for people to go to hospital or speed up their recovery.

They will recruit patients aged over 65 years (or aged 50-64 years with underlying health conditions), who consult in primary care (this trial is a national platform trial and is potentially available to all GP practices in the UK) and have COVID-19 symptoms. Patients will be tested for COVID-19 where possible, and will receive either the usual care provided plus hydroxychloroquine 200mg twice a day for 7 days, or, soon, azithromycin for 3-5 days, or usual supportive care without any experimental treatment. The trial aims to recruit over 3,000 people, and has been designed to be flexible, so new suitable treatments can be added into the trial when these become available.

Professor Matthew Snape, Oxford Vaccine Group, £0.6 million: With Public Health England, they will use an existing study of infectious disease immunity in children and teenagers 0 to 19 years old to study the presence of antibodies against COVID-19 (a marker of having had the disease and now having immunity) in approximately 400 children and teenagers per month for the duration of the COVID-19 outbreak, and they will collect information on recent respiratory illnesses and relevant medical history.

Professor Trudie Lang, Nuffield Department of Medicine, £0.3 million: Building on lessons learnt in the Zika and Ebola outbreaks, the Global Health Network will deliver and share trusted research tools, guidance and training, for example providing guidance on how to run studies in local clinics and hospitals. They will work with partners internationally to create lasting research networks to support evidence generation in challenging settings, so that better quality, standardised data is shared faster worldwide.

Professor Sally Sheard, University of Liverpool, and Dr Nina Gobat, Nuffield Department of Primary Care Health Sciences, £0.3 million: Working with colleagues at the University of Oxford, they will analyse the UK pandemic response by collecting real-time responses from senior policymakers and stakeholders (PHE, DHSC, NHS) and the frontline experiences of healthcare workers, and by studying media and document sources. Their findings will inform senior policymakers.

Dr Sumana Sanyal, Sir William Dunn School of Pathology, £0.2 million: The virus, SARS-CoV-2, uses enzymes within infected cells called proteases (enzymes which cut up other proteins), so it can replicate and spread. This study will identify which proteases are necessary for the virus, to provide targets for future drugs and vaccine development.”
https://www.research.ox.ac.uk/Article/2020-04-17-covid-19-mortality-highly-influenced-by-age-demographics

Alembic Pharmaceuticals announces USFDA Tentative Approval for Alcaftadine Ophthalmic Solution, 0.25%.

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Alembic Pharmaceuticals announces USFDA Tentative Approval for Alcaftadine Ophthalmic Solution, 0.25%.

April 20, 2020: “Alembic Pharmaceuticals Limited (Alembic) announced it has received tentative approval from the US Food & Drug Administration (USFDA) for its Abbreviated New Drug Application (ANDA) Alcaftadine Ophthalmic Solution, 0.25%. The approved ANDA is therapeutically equivalent to the reference listed drug product (RLD) Lastacaft Ophthalmic Solution, 0.25%, of Allergan, Inc. (Allergan).

Alcaftadine Ophthalmic Solution is an H1 histamine receptor antagonist indicated for the prevention of itching associated with allergic conjunctivitis. Alcaftadine Ophthalmic Solution, 0.25% has an estimated market size of US$ 7 million for twelve months ending December 2019 according to IQVIA. Alembic has a cumulative total of 120 ANDA approvals (107 final approvals and 13 tentative approvals) from USFDA.”

https://www.alembicpharmaceuticals.com/wp-content/uploads/2020/04/Press-Release-USFDA-Tentative-Approval-for-Alcaftadine-Ophthalmic-Solution-April-2020.pdf

Bristol Myers Squibb Announces Positive Topline Result from Pivotal Phase 3 Trial Evaluating Opdivo® (nivolumab) plus Yervoy® (ipilimumab) vs. Chemotherapy in Previously Untreated Malignant Pleural Mesothelioma

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Bristol Myers Squibb Announces Positive Topline Result from Pivotal Phase 3 Trial Evaluating Opdivo® (nivolumab) plus Yervoy® (ipilimumab) vs. Chemotherapy in Previously Untreated Malignant Pleural Mesothelioma

April 20, 2020: “Bristol-Myers Squibb announced that CheckMate -743, a pivotal Phase 3 trial evaluating Opdivo ® (nivolumab) in combination with Yervoy ® (ipilimumab) in previously untreated malignant pleural mesothelioma (MPM) met its primary endpoint of overall survival (OS). Based on a pre-specified interim analysis conducted by the independent Data Monitoring Committee, Opdivo in combination with Yervoy resulted in a statistically significant and clinically meaningful improvement in OS compared to chemotherapy (pemetrexed and cisplatin or carboplatin).

The safety profile of Opdivo plus Yervoy observed in the trial reflects the known safety profile of the combination.

“Malignant pleural mesothelioma is a devastating disease that has seen limited treatment advances over the past decade,” said Sabine Maier, M.D., development lead, thoracic cancers, Bristol Myers Squibb.“These topline results from the CheckMate -743 trial demonstrate the potential of Opdivo plus Yervoy in previously untreated patients with malignant pleural mesothelioma, and is another example of the established efficacy and safety of the dual immunotherapy combination seen in multiple tumor types. We would like to thank the patients who participated in this trial, as well as the investigators and site personnel for their perseverance during the conduct of this study and in delivering this important result for patients in the midst of the COVID-19 pandemic. We look forward to working with investigators to present the results at a future medical meeting, and to discussing them with health authorities.”

CheckMate -743 is an open-label, multi-center, randomized Phase 3 trial evaluating Opdivo plus Yervoy compared to chemotherapy (pemetrexed and cisplatin or carboplatin) in patients with previously untreated malignant pleural mesothelioma (MPM). Opdivo is administered at 3 mg/kg every two weeks and Yervoy at 1 mg/kg every six weeks. The primary endpoint of the trial was OS. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and efficacy measures according to PD-L1 expression level.

Malignant pleural mesothelioma is a rare but aggressive form of cancer that forms in the lining of the lungs. It is most frequently caused by exposure to asbestos. Diagnosis is often delayed, with the majority of patients having advanced or metastatic disease at presentation. Prognosis is generally poor: in previously untreated patients with advanced or metastatic malignant pleural mesothelioma, median survival is less than one year and the five-year survival rate is approximately 10%.”
https://news.bms.com/press-release/corporatefinancial-news/bristol-myers-squibb-announces-positive-topline-result-pivotal

Interim phase 1 data evaluating MOv18 IgE, an anti-folate receptor alpha IgE antibody, in cancer patients with advanced solid tumours to be presented at the AACR Virtual Annual Meeting

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Interim phase 1 data evaluating MOv18 IgE, an anti-folate receptor alpha IgE antibody, in cancer patients with advanced solid tumours to be presented at the AACR Virtual Annual Meeting

April 20, 2020: “Epsilogen, a global leader in the development of immunoglobulin E (IgE) antibodies to treat cancer, today announces that interim data from the ongoing phase 1 clinical study of MOv18 IgE will be presented at the forthcoming American Association for Cancer Research (AACR) Virtual Annual Meeting I, 27-28 April 2020. This study, funded, sponsored and conducted by Cancer Research UK’s Centre for Drug Development, is evaluating MOv18 IgE, a first-in-class IgE antibody, in patients with advanced cancer expressing folate receptor alpha (FR alpha). This receptor is known to be overexpressed on the surface of certain cancer cells, most commonly ovarian cancer. MOv18 IgE is the first therapeutic IgE antibody to enter clinical trials.

The presentation at the AACR meeting will be made by Professor James Spicer of King’s College London (KCL), UK, one of the scientific founders of Epsilogen and lead investigator of the phase 1 study. As announced separately today, Epsilogen has in-licensed MOv18 IgE from KCL, where it was originally developed in collaboration with Cancer Research UK.

Outline of the phase 1 clinical study (NCT number: NCT02546921)

This multi-centre, dose escalation, phase 1 study, enrols patients with histologically, or cytologically-proven, advanced, unresectable solid tumours where FR alpha expression on their tumour was detected in a previous biopsy. Patients are administered their allocated dose of MOv18 IgE by IV infusion. The primary objective of the study is safety and tolerability of the study drug. Secondary objectives are anti-tumour activity, as measured by the Response Evaluation Criteria in Solid Tumours (RECIST) and assessment of disease response, using CA 125 tumour marker.”
https://epsilogen.com/interim-phase-1-data-evaluating-mov18-ige/

Epsilogen licences MOv18 IgE, an anti-folate receptor alpha IgE antibody from King’s College London

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Epsilogen licences MOv18 IgE, an anti-folate receptor alpha IgE antibody from King’s College London

April 20, 2020: “Epsilogen, a global leader in the development of immunoglobulin E (IgE) antibodies to treat cancer announces that it has in-licenced exclusive global rights to MOv18 IgE, an anti-folate receptor alpha IgE antibody from King’s College London (KCL). Financial terms of the agreement have not been disclosed.

The antibody, which was developed at KCL in collaboration with Cancer Research UK, is the first therapeutic IgE antibody to enter clinical trials. Cancer Research UK is funding, sponsoring and conducting an on-going phase I clinical trial in patients with advanced cancer expressing folate receptor alpha (FR alpha).

As separately announced today, interim data from this trial will be presented at the forthcoming American Association for Cancer Research (AACR) Virtual Annual Meeting I which begins on 27 April 2020. Folate receptor alpha (FR alpha) is selectively expressed most commonly on the surface of ovarian cancer cells, making it a promising target for IgE antibody therapy for this cancer which has relatively few effective treatment alternatives.

Epsilogen will continue the further clinical development of MOv18 IgE and has put in place a comprehensive manufacturing programme with a leading contract development and manufacturing organisation. Funding for this manufacturing work has been provided by a further £3 million Series A2 investment from Epsilogen’s existing investors Epidarex Capital, ALSA Holdings and the UCL Technology Fund.

Dr Tim Wilson, Chief Executive Officer of Epsilogen, said: “We are very pleased to have in-licensed this promising new therapy which has the potential to target a very serious cancer with relatively few effective treatment alternatives. We are grateful to our scientific founders Professors Sophia Karagiannis and James Spicer of KCL for conducting the early scientific research on MOv18 IgE and also to Cancer Research UK for investing in and developing the product through its early clinical phase. We also wish to thank our investor group for continuing to support us with further financing via the Series A2.”

King’s College London is one of the top 10 UK universities in the world (QS World University Rankings, 2018/19) and among the oldest in England. King’s has more than 31,000 students (including more than 12,800 postgraduates) from some 150 countries worldwide, and some 8,500 staff.

King’s has an outstanding reputation for world-class teaching and cutting-edge research. In the 2014 Research Excellence Framework (REF), eighty-four per cent of research at King’s was deemed ‘world-leading’ or ‘internationally excellent’ (3* and 4*).”
World-changing ideas. Life-changing impact: https://www.kcl.ac.uk/news/headlines.aspx
https://epsilogen.com/epsilogen-licences-mov18-ige/

WHO guidance helps detect iron deficiency and protect brain development

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WHO guidance helps detect iron deficiency and protect brain development

April 20, 2020: “Detecting iron deficiency early during pregnancy and in young children is crucial. Iron deficiency in children under two years of age can have significant and irreversible effects on brain development. This can lead to negative consequences on learning and school performance later in life.

Cognitive development of a child can also be affected if a mother is iron deficient during her last trimester of pregnancy. New World Health Organization guidelines on the use of ferritin concentrations to assess iron status in individuals and populations will help health workers to detect iron deficiency early and avoid the most severe impacts. 

WHO shows how to best measure ferritin, an indicator of iron stores, to help determine iron deficiency or overload. Ferritin is a protein which can be found in small amounts circulating in a person’s blood. Ferritin levels are low in iron-deficient individuals and high in iron-loaded individuals. Accurate measurements of this protein, along with clinical and laboratory evaluation, can guide the appropriate interventions in both individual patients and at a population level.

“Reducing anemia is one of the components of our efforts to eradicate all forms of malnutrition. However, progress has been limited and we still have 614 million women and 280 million children globally who suffer from it,” said Dr Francesco Branca, Director of the Department of Nutrition and Food Safety at WHO. “Iron deficiency is a major determinant of anemia and measuring ferritin, a key biomarker of iron metabolism, will help us better target and evaluate our action to fight anemia”

Iron is an essential element with important functions such as oxygen transport, DNA synthesis and muscle metabolism. Iron deficiency is the main cause of anaemia, which is the most prevalent nutritional deficiency worldwide, affecting 33% of non-pregnant women, 40% of pregnant women, and 42% of children worldwide.

In adults, iron deficiency can also have negative effects including fatigue, impaired physical performance and decreased work productivity, as well as impacting social activities. Iron deficiency occurs mainly when the requirements of iron increase during rapid periods of growth and development such as in early childhood, adolescence and pregnancy, but it can occur at other stages in life. In pregnant women, iron deficiency can cause anaemia, reduced birth weight and reduced gestation periods.

The new guidelines also cover the early detection of iron overload. Iron overload (accumulation of iron in the body) is generally the result of disorders such as hereditary haemochromatosis, thalassaemia, repeated blood transfusions or other conditions that affect iron absorption or regulation and can also lead to deterioration of a person’s health if left untreated.

Improved knowledge about the prevalence and distribution of iron deficiency and risk of iron overload in the population helps countries to decide on appropriate interventions, and to monitor and evaluate the impact and safety of public health programmes. For example, nutritional iron deficiency can be commonly found in populations that also have infectious diseases. The adequate evaluation of iron status in countries with infectious disorders can help countries to put in place adequate health policies.

The WHO guidelines aim to help WHO Member States and their partners to make evidence-informed decisions on appropriate actions in their efforts to lower iron deficiency and improve the health and quality of life of individuals and populations.”
https://www.who.int/news-room/detail/20-04-2020-who-guidance-helps-detect-iron-deficiency-and-protect-brain-development

Sanofi to present Phase 2 detailed results of its brain-penetrant BTK inhibitor in relapsing multiple sclerosis

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Sanofi to present Phase 2 detailed results of its brain-penetrant BTK inhibitor in relapsing multiple sclerosis

April 17, 2020: “Sanofi will host a scientific session to present detailed data from their Phase 2b trial evaluating its investigational BTK (Bruton’s tyrosine kinase) inhibitor (SAR442168), an oral, brain-penetrant, selective small molecule. In February, the company reported that the study’s primary endpoint was met, demonstrating that the BTK inhibitor significantly reduced disease activity associated with multiple sclerosis (MS) as measured by magnetic resonance imaging.

“During these unprecedented times we remain committed to sharing results that allow us to advance the understanding of multiple sclerosis and the impact our potential brain-penetrant BTK inhibitor could have on the lives of people living with this disease,” said John C. Reed, M.D. Ph.D. Sanofi’s Global Head of Research & Development.  “Our virtual session will provide the opportunity for an important scientific exchange and a forum for sharing the recent clinical results obtained with our brain-penetrant BTK inhibitor for multiple sclerosis.”

Sanofi is hosting this scientific session as a result of the cancellation of the live American Academy of Neurology (AAN) annual meeting due to the COVID-19 pandemic. The virtual scientific session will be held on April 23 from 8:00-9:00am EST/2:00-3:00pm CET; to register, click here. No pre-registration available for the event.

Audio webcast and conference call will be open to healthcare professionals and healthcare media. It will include presentations followed by Q&A session and live access to the speakers including: Daniel Reich, MD, PhD, Senior Investigator at NIH and Chief of the Translational Neuroradiology Section in the National Institute of Neurological Disorders and Stroke; Ross Gruber, PhD, Principal Scientist at Sanofi Genzyme; and Anthony Traboulsee, MD, Professor and Research Chair of the MS Society of Canada at the University of British Columbia in Vancouver, Canada

Topics to be highlighted which were planned to be presented at AAN:

  • BTK inhibitor mechanism of action and preclinical data
  • Phase 2b trial design
  • Phase 2b efficacy and safety results             In the US and Europe, there are approximately 1.2 million people diagnosed with MS, an unpredictable, chronic disease that attacks the central nervous system. Despite current treatments, many people with MS continue to accumulate disability, and one in four suffer from progressive forms of the disease with limited or no treatments available.”
    https://www.sanofi.com/en/media-room/press-releases/2020/2020-04-17-07-00-00
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