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Calquence reduced the risk of disease progression or death by 71%

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Calquence reduced the risk of disease progression or death by 71%

December 12, 2021: “Updated results from the ASCEND Phase III trial showed AstraZeneca’s Calquence (acalabrutinib) maintained a statistically significant progression-free survival (PFS) benefit at three years compared to investigator’s choice of rituximab combined with either idelalisib (IdR) or bendamustine (BR) in adults with relapsed or refractory chronic lymphocytic leukaemia (CLL), the most common type of leukaemia in adults.

These data, presented at the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition, demonstrated Calquence reduced the risk of disease progression or death by 71% versus IdR/BR as assessed by investigators at three years (based on a hazard ratio [HR] of 0.29; 95% confidence interval [CI]: 0.21-0.41; p<0.0001).

Similar clinical benefits were observed in an exploratory analysis comparing each regimen with Calquence. Safety and tolerability of Calquence were consistent with earlier findings, with no new safety signals identified.

Additional safety analyses from the ELEVATE-RR Phase III trial were also presented at ASH to further characterise adverse events (AEs) related to treatment with Bruton’s tyrosine kinase (BTK) inhibitors Calquence and ibrutinib.

Overall, patients on ibrutinib experienced a 37% higher burden of AEs of any grade versus patients on Calquence.

For any grade atrial fibrillation/flutter, a key secondary endpoint in the ELEVATE-RR trial, median time to onset was longer for Calquence versus ibrutinib (28.8 versus 16.0 months), and cumulative incidence was lower at all timepoints from six months through two years.

Additionally, the ELEVATE-RR Phase III trial showed incidence of all-grade atrial fibrillation/flutter was lower for Calquence across subgroups of age, prior line of therapy and among patients without prior history of heart complications.

Atrial fibrillation is an irregular heart rate that can increase the risk of stroke, heart failure and other heart-related complications.

John F. Seymour, MBBS PhD, Peter MacCallum Centre and the Royal Melbourne Hospital, and a lead investigator on the ELEVATE-RR trial, said: “Patients with relapsed or refractory chronic lymphocytic leukaemia face limited options to successfully manage their disease, as they are often older and dealing with significant comorbidities.

The risk of cardiac adverse events is an important consideration, especially for treatment with Bruton’s tyrosine kinase inhibitors because they can produce significant morbidity in some casesand also lead patients to discontinue treatment.

The ELEVATE-RR data provide compelling evidence that acalabrutinib is a more tolerable option with reduced cardiovascular toxicity, giving clinicians further reassurance when prescribing this medicine that fewer patients will need to cease treatment due to adverse events, thus maintaining ongoing control of their disease, even in this complex setting.”

Anas Younes, Senior Vice President, Haematology R&D, AstraZeneca, said: “These impressive new long-term data support Calquence as the preferred therapy for the most common type of leukaemia in adults, with favourable safety compared to the current standards of care.

The totality of the ASCEND and ELEVATE-RR data, in addition to data introducing a new tablet formulation for patients who need alternative methods of taking Calquence, continues to reinforce the positive experience that this medicinecan deliver for patients with chronic lymphocytic leukaemia.”

https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/calquence-reduced-the-risk-of-disease-progression-or-death-vs-standard-of-care-combinations-at-three-years-in-the-ascend-phase-iii-trial.html

Positive Phase 3 Dupixent® data in children 6 months to 5 years with moderate-to-severe atopic dermatitis featured in RAD 2021

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Positive Phase 3 Dupixent® data in children 6 months to 5 years with moderate-to-severe atopic dermatitis featured in RAD 2021

December 13, 2021: “Positive Phase 3 results show adding Dupixent® (dupilumab) to standard-of-care topical corticosteroids (TCS) significantly improved skin clearance and reduced overall disease severity and itch in infants and children aged 6 months to 5 years with uncontrolled moderate-to-severe atopic dermatitis.

These data will be presented today in a late-breaking session at the 2021 Revolutionizing Atopic Dermatitis Conference (RAD 2021).

“One of most challenging aspects of my job as a physician is having limited treatment options to help babies and young children suffering from moderate-to-severe atopic dermatitis, which can disrupt their ability to fully thrive in these early years of life,” says Amy S. Paller, M.D, Walter J. Hamlin Professor and Chair of Dermatology and Professor of Pediatrics at Northwestern University Feinberg School of Medicine, and principal investigator of the trial. 

“These results show dupilumab can significantly improve the signs and overall severity of atopic dermatitis in children as young as 6 months. Safety is of paramount importance when treating children at such a young age. 

We are encouraged that these data show a safety profile consistent with what has been seen in other age groups. We will continue to follow these patients for up to 5 years in an open-label trial.”

Eighty-five to 90% of patients with atopic dermatitis develop symptoms before the age of 5, which can often continue through adulthood.

Symptoms include intense, persistent itch and skin lesions that cover much of the body (58% on average for the patients in this trial at baseline), resulting in skin dryness, cracking, redness or darkening, and crusting and oozing, along with increased risk of skin infections.

Moderate-to-severe atopic dermatitis may also significantly impact the quality of life of a young child, their parents and caregivers.

In addition, the underlying type 2 inflammation involved in atopic dermatitis can contribute to the development of other diseases like asthma and certain allergies, that may also appear throughout a person’s life.

Topline results from the randomized, placebo-controlled pivotal trial, which met all primary and secondary endpoints, were announced in August 2021.

Data presented at RAD 2021 showed that at 16 weeks, patients who added Dupixent to low-potency TCS experienced the following, compared to TCS alone (placebo):

  • 28% achieved clear or almost-clear skin compared to 4% with placebo (p<0.0001), the primary endpoint.
  • 53% achieved 75% or greater improvement in overall disease severity from baseline compared to 11% with placebo (p<0.0001), the co-primary endpoint outside of the U.S.
  • 49% average improvement from baseline in itch compared to 2% improvement with placebo (p<0.0001).
  • 70% average improvement from baseline in overall disease severity (EASI) compared to 20% improvement with placebo (p<0.0001).

The safety profile observed in the randomized, placebo-controlled trial was consistent with the well-established safety profile of Dupixent in adults, adolescents and children 6 years and older with moderate-to-severe atopic dermatitis.

Overall rates of adverse events (AEs) were 64% for Dupixent and 74% for placebo. Most common AEs and AEs of special interest included nasopharyngitis (8% Dupixent, 9% placebo), upper respiratory tract infection (6% Dupixent, 8% placebo), conjunctivitis (5% Dupixent, 0% placebo), herpes viral infections (6% Dupixent, 5% placebo).

These results will form the basis of global regulatory submissions for this age group, beginning with the U.S. in 2021 and European Union in the first half of 2022.

Additionally, long-term data from the Phase 3 trial in patients aged 6 to 11 years with moderate-to-severe atopic dermatitis will also be presented in a late-breaking session. Efficacy and safety results at one year were consistent with the known profile of Dupixent in atopic dermatitis.

The data from these trials add to the extensive LIBERTY AD clinical program – the largest Phase 3 clinical trial program in atopic dermatitis, involving approximately 3,500 infants, children, adolescents and adults to date.

Dupixent is the first biologic medicine to demonstrate positive results in this young patient population. The efficacy and safety of Dupixent in children below the age of 6 years have not been fully evaluated by any regulatory authority.

About the Dupixent Trial

LIBERTY AD PRESCHOOL is a two-part Phase 2/3 trial.

The Phase 3 randomized, double-blind, placebo-controlled part of the trial (Part B) evaluated the efficacy and safety of Dupixent added to standard-of-care low-potency TCS compared to low-potency TCS alone (placebo) in 162 children aged 6 months to 5 years with uncontrolled moderate-to-severe atopic dermatitis.

The primary endpoints assessed the proportion of patients achieving an Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) and 75% improvement in Eczema Area and Severity Index (EASI-75) at week 16.

EASI measures extent and severity of the disease. Itch was assessed using a caregiver-reported 0 to 10 Numerical Rating Scale.

Patients treated with Dupixent received either 200 mg (for children weighing ≥5 to <15 kg) or 300 mg (for children weighing ≥15 to <30 kg) every four weeks.

In total, there were 162 patients in the trial (83 Dupixent, 79 in the placebo), the average age was 3.8 years and 61% were male. Approximately 12% of patients were Latino/Hispanic and 19% were Black/African American.

At the start of the trial 77% of patients had severe disease and 29% had previously used systemic immunosuppressants for their atopic dermatitis and on average, patients entered the trial with atopic dermatitis covering 58% of their body.

Furthermore, 81% of these patients had at least one concurrent type 2 inflammatory and/or allergic condition such as allergic rhinitis and asthma.

Part B of the Phase 3 trial was informed by Part A, which was an open-label, single-ascending-dose, sequential cohort Phase 2 trial designed to assess the pharmacokinetics and safety of Dupixent in children aged 6 months to 5 years with uncontrolled severe atopic dermatitis.

Children who completed Part A or Part B of the trial were eligible to enroll in an open-label extension trial to assess the safety and efficacy of long-term treatment with Dupixent in this age group for an additional five years.”

https://www.sanofi.com/en/media-room/press-releases/2021/2021-12-13-07-00-00-2350402

CITYSCAPE trial show positive results with Roche’s novel anti-TIGIT tiragolumab plus Tecentriq

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CITYSCAPE trial show positive results with Roche’s novel anti-TIGIT tiragolumab plus Tecentriq

December 2021: “Roche announced new follow-up efficacy, safety and patient-reported outcomes (PROs) data from the phase II CITYSCAPE trial, investigating the novel anti-TIGIT cancer immunotherapy tiragolumab plus Tecentriq® (atezolizumab) compared with Tecentriq alone as an initial (first-line) treatment for people with PD-L1-positive metastatic non-small cell lung cancer (NSCLC).

The full results are being featured as an oral presentation in the Proffered Paper session 2 (Abstract LBA2) at the European Society for Medical Oncology (ESMO) Immuno-Oncology Congress 2021, taking place 8-11 December.

“These encouraging results suggest that combining anti-TIGIT and anti-PD-L1 cancer immunotherapies such as tiragolumab and Tecentriq could potentially represent a novel approach to address unmet needs in cancer,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development.

“With tiragolumab, we have the largest and most advanced anti-TIGIT clinical programme, and we look forward to the results of our phase III trials in lung cancer and other challenging tumour types.”

After 2.5 years median follow-up, tiragolumab plus Tecentriq continued to show an improvement in the intention-to-treat (ITT) population (n=67), driven by the PD-L1-high population (TPS ≥ 50%) (n=29).

In the ITT population, the combination reduced the risk of disease worsening or death (progression-free survival; PFS) by 38% (median PFS=5.6 vs. 3.9 months; hazard ratio (HR)=0.62, 95% CI: 0.42-0.91) and improved overall response rates (ORR) (38.8% vs. 20.6%) compared with Tecentriq alone.

A predefined exploratory analysis in the PD-L1-high population showed a 71% reduction in the risk of disease worsening or death (median PFS=16.6 vs. 4.1 months; HR=0.29, 95% CI: 0.15-0.53) and a clinically meaningful improvement in ORR (69% vs. 24.1%) with the combination compared with Tecentriq alone.

The analysis also showed that tiragolumab plus Tecentriq improved overall survival (OS), a secondary endpoint of the study, in the ITT population, which was driven by the PD-L1-high population.

After 2.5 years median follow-up, median OS was 23.2 vs. 14.5 months (HR=0.69, 95% CI: 0.44-1.07) in the ITT population.

The exploratory data in the PD-L1-high population showed a clinically meaningful OS improvement.

The median was not reached for the tiragolumab regimen and is projected to be greater than 30.3 months based on the lower confidence interval (NE (30.3-NE) vs. 12.8 months (4.7-24.2); HR=0.23, 95% CI: 0.10-0.53).

Data suggest that the combination was generally well-tolerated, showing similar rates of Grade 3-4 treatment-related adverse events (AEs) when adding tiragolumab to Tecentriq compared with Tecentriq alone (22.4% vs. 25%).

The most common all cause AEs (rate greater than 5% difference between study groups) seen with the combination were infusion-related reactions, stiffness, dry skin, fatigue and rash.

After longer follow-up, no new safety signals were observed with the combination. Patients generally reported minimal-to-moderate symptoms and generally maintained their quality of life compared with the start of treatment.

PRO data from this exploratory analysis showed that lung symptoms, such as dyspnoea and pain, did not appear to deteriorate with the addition of tiragolumab to Tecentriq.

CITYSCAPE study forms the basis of an industry-leading development programme across multiple settings and tumour types.

The phase III SKYSCRAPER-01 trial is currently ongoing to confirm these results in the PD-L1-high population, with the goal of bringing this treatment option to patients.

Earlier this year, tiragolumab was granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration – representing the first anti-TIGIT therapy to be granted this designation and the 37th BTD for Roche’s portfolio of medicines.

Since 2020, Roche has initiated five phase III trials evaluating tiragolumab plus Tecentriq in early and metastatic disease in lung (SKYSCRAPER-01, SKYSCRAPER-02, SKYSCRAPER-03) and oesophageal cancers (SKYSCRAPER-07, SKYSCRAPER-08).

Tiragolumab is also being evaluated in other solid tumours as well as in haematological cancers.

About the CITYSCAPE study
CITYSCAPE is a global phase II, randomised and blinded study evaluating tiragolumab plus Tecentriq® (atezolizumab) compared with Tecentriq alone in 135 patients with first-line PD-L1-positive locally advanced, unresectable or metastatic non-small cell lung cancer.

Patients were randomised 1:1 to receive either tiragolumab plus Tecentriq or placebo plus Tecentriq, until progressive disease or loss of clinical benefit. Co-primary endpoints are overall response rate (ORR) and progression-free survival (PFS).

Secondary endpoints include safety, overall survival (OS) and patient-reported outcomes (PROs).

PRO results were assessed with EORTC QLQ-C30, a questionnaire developed to assess the quality of life of people with cancer, administered at baseline and throughout study treatment.

A summary of the results are as follows:

 ITTPD-L1 TPS > 50%PD-L1 TPS 1–49%
 Placebo plus TecentriqTiragolumab plus

Tecentriq		Placebo plus TecentriqTiragolumab plus

Tecentriq		Placebo plus TecentriqTiragolumab plus

Tecentriq
N686729293938
ORR, %20.638.824.169.017.915.8
mDOR, mo

(95% CI)		10.7

(6.0-18.8)		17.6

(9.1-26.1)		8.2

(5.6-10.4)		15.7

(9.1-NE)		18.8

(15.9-22.8)		17.8

(8.3-24.2)
mPFS, mo

(95% CI)		3.9

(2.7-4.5)		5.6

(4.2-10.4)		4.1

(2.1-6.8)		16.6

(5.5-22.3)		3.6

(1.4-5.5)		4.0

(1.6-5.6)
HR

(95% CI)		0.62*

(0.42-0.91)		0.29†

(0.15-0.53)		1.07†

(0.67-1.71)
mOS, mo

(95% CI)		14.5

(9.6-20.4)		23.2

(14.1-31.5)		12.8

(4.7-24.2)		NE

(30.3-NE)		14.5

(8.3-25.6)		13.3

(8.0-20.7)
HR

(95% CI)		0.69*

(0.44-1.07)		0.23†

(0.10-0.53)		1.16†

(0.70-1.94)

*Stratified; †Unstratified; NE = non-evaluable.

 Placebo

plus Tecentriq

n=68		Tiragolumab

plus Tecentriq

n= 67
All cause AEs
Grade 3-4

Grade 5		66 (97.1%)

27 (39.7%)

7 (10.3%)		66 (98.5%)

35 (52.2%)

3 (4.5%)
Treatment-related AEs

Grade 3-4

Grade 5		48 (70.6%)

17 (25%)

0		55 (82.1%)

15 (22.4%)

2 (3%)
Immune mediated AEs
Grade 3-4		32 (47.1%)

11 (16.2%)		51 (76.1%)

13 (19.4%)
AEs leading to withdrawal9 (13.2%)10 (14.9%)


About tiragolumab
Tiragolumab is a first-in-class novel immune checkpoint inhibitor with an intact Fc region. Tiragolumab selectively binds to TIGIT, a novel inhibitory immune checkpoint which suppresses the immune response to cancer.

Based on preclinical research, tiragolumab is thought to work as an immune amplifier with other cancer immunotherapies such as Tecentriq.

The TIGIT pathway is distinct but complementary to the PD-L1/PD-1 pathway. Dual blockade with tiragolumab and Tecentriq may help overcome immune suppression and restore the immune response.

About Tecentriq® (atezolizumab)
Tecentriq is a monoclonal antibody designed to bind with a protein called Programmed Death Ligand-1 (PD-L1), which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T-cells.

Tecentriq is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

The development of Tecentriq and its clinical programme is based on our greater understanding of how the immune system interacts with tumours and how harnessing a person’s immune system combats cancer more effectively.

Tecentriq is approved in the US, EU and countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of NSCLC, SCLC, certain types of metastatic urothelial cancer, in PD-L1-positive metastatic triple-negative breast cancer and for hepatocellular carcinoma.

In the US, Tecentriq is also approved in combination with Cotellic® (cobimetinib) and Zelboraf® (vemurafenib) for the treatment of people with BRAF V600 mutation-positive advanced melanoma.”

https://www.roche.com/media/releases/med-cor-2021-12-10.htm

FDA Expands Eligibility for Pfizer-BioNTech COVID-19 Booster Dose to 16- and 17-Year-Olds

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FDA Expands Eligibility for Pfizer-BioNTech COVID-19 Booster Dose to 16- and 17-Year-Olds

December 09, 2021: “The U.S. Food and Drug Administration amended the emergency use authorization (EUA) for the Pfizer-BioNTech COVID-19 Vaccine, authorizing the use of a single booster dose for administration to individuals 16 and 17 years of age at least six months after completion of primary vaccination with the Pfizer-BioNTech COVID-19 Vaccine. 

“Vaccination and getting a booster when eligible, along with other preventive measures like masking and avoiding large crowds and poorly ventilated spaces, remain our most effective methods for fighting COVID-19,” said Acting FDA Commissioner Janet Woodcock, M.D.

“As people gather indoors with family and friends for the holidays, we can’t let up on all the preventive public health measures that we have been taking during the pandemic. With both the delta and omicron variants continuing to spread, vaccination remains the best protection against COVID-19.” 

On Nov. 19, the FDA authorized the use of a single booster dose of the Pfizer-BioNTech COVID-19 Vaccine for administration to all individuals 18 years of age and older after completion of primary vaccination with any FDA-authorized or approved COVID-19 vaccine.

Today’s action expands the use of a single booster dose of the Pfizer-BioNTech COVID-19 Vaccine for administration to individuals 16 and 17 years of age at least six months after completion of a primary series of the Pfizer-BioNTech COVID-19 Vaccine.

The FDA-authorized Pfizer-BioNTech COVID-19 Vaccine and the FDA-approved Comirnaty (COVID-19 Vaccine, mRNA) are the only COVID-19 vaccines currently available for the 16- and 17- year-old age group.

Individuals who are 16 and 17 years of age should only receive the Pfizer-BioNTech COVID-19 Vaccine or Comirnaty as their booster dose.

“The Pfizer-BioNTech COVID-19 Vaccine has been available to individuals 16 years of age and older for nearly a year, and its benefits have been shown to clearly outweigh potential risks,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research.

“Since we first authorized the vaccine, new evidence indicates that vaccine effectiveness against COVID-19 is waning after the second dose of the vaccine for all adults and for those in the 16- and 17-year-old age group.

A single booster dose of the vaccine for those vaccinated at least six months prior will help provide continued protection against COVID-19 in this and older age groups.”

Data Supporting Effectiveness

The EUA for a single booster dose of the Pfizer-BioNTech COVID-19 Vaccine for individuals 16 and 17 years of age is based on the FDA’s previous analysis of immune response data that supported use of a booster dose in individuals 18 years of age and older. 

The FDA had analyzed the immune response data from approximately 200 participants, 18 through 55 years of age, who received a single booster dose approximately six months after their second dose.

The antibody response against the SARS-CoV-2 virus one month after a booster dose of the vaccine, when compared to the response one month after the two-dose primary series in the same individuals, demonstrated a booster response.

The FDA’s assessment of the effectiveness of a booster dose for individuals 16 and 17 years of age is based on these data.

Based on the available data for individuals 18 and older regarding effectiveness, the FDA has concluded that these data support extending the eligible booster age population to 16- and 17-year-olds. 

FDA Evaluation of Benefits and Risks

In the time since Pfizer initially submitted safety and effectiveness data on a single booster dose following the two-dose primary series to the FDA, additional real-world data have become available on the increasing number of cases of COVID-19 in the U.S. and on the risk of myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the outer lining of the heart) following vaccination with the Pfizer-BioNTech COVID-19 Vaccine.

These additional data enabled the FDA to reassess the benefits and risks of the use of the vaccine in a wider population.

The FDA has determined that the benefits of a single booster dose of the Pfizer-BioNTech COVID-19 Vaccine or Comirnaty outweigh the risks of myocarditis and pericarditis in individuals 16 and 17 years of age to provide continued protection against COVID-19 and the associated serious consequences that can occur including hospitalization and death.

Pfizer is conducting post-authorization/post-marketing studies to assess known serious risks of myocarditis and pericarditis.

In addition, the FDA and the Centers for Disease Control and Prevention have several systems in place to continually monitor COVID-19 vaccine safety and allow for the rapid detection and investigation of potential safety concerns.

The fact sheets for recipients and caregivers and for healthcare providers contain information about the potential side effects, as well as the risk of myocarditis and pericarditis.

The most commonly reported side effects by individuals who received a booster dose were pain, redness and swelling at the injection site, as well as fatigue, headache, muscle or joint pain and chills.

Of note, swollen lymph nodes in the underarm were observed more frequently following the booster dose than after the second dose of a two-dose primary series. 

The FDA did not hold a meeting of the Vaccines and Related Biological Products Advisory Committee on today’s action, as the agency previously convened the committee for extensive discussions regarding the use of booster doses of COVID-19 vaccines and, after review of Pfizer’s EUA request, the FDA concluded that the request does not raise questions that would benefit from additional discussion by committee members.

The FDA will be publicly posting documents regarding the agency’s decision on its website following authorization. 

The amendment to the EUA was granted to Pfizer Inc.”

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-expands-eligibility-pfizer-biontech-covid-19-booster-dose-16-and-17

FDA Issues Improvement Plan Focused on Modernizing Foodborne Illness Outbreak Responses

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FDA Issues Improvement Plan Focused on Modernizing Foodborne Illness Outbreak Responses

December 09, 2021: “The U.S. Food and Drug Administration has a longstanding commitment to strengthening food safety and better protecting consumers, as part of its public health agenda.

Today, we are taking an important step to build on this commitment with the release of the Foodborne Outbreak Response Improvement Plan.

This plan is designed to help the FDA and our partners enhance the speed, effectiveness, coordination and communication of foodborne outbreak investigations. We are confident that the actions outlined in this plan will in turn translate into activities focused on enhancing the prevention of outbreaks.

As part of our work implementing the FDA Food Safety Modernization Act (FSMA) and our New Era of Smarter Food Safety initiative, we have collaborated with experts in both the public and private sectors for input on additional ways to strengthen the agency’s outbreak response.

Input from the U.S. Department of Agriculture’s Food Safety Inspection Service (FSIS) and the Centers for Disease Control and Prevention, state health officials, industry and consumer foodborne outbreak experts, along with the input of FDA leadership and staff, was key to the development of our new improvement plan. 

The agency also contracted with the University of Minnesota’s School of Public Health to assess the FDA’s capacity to support, join, or lead multistate outbreak investigations and to provide recommendations in an independent report, which we are also making public today.

This report played an important role in the development of our new plan.

The Foodborne Outbreak Response Improvement Plan focuses on four specific priority areas in which improvements will have the most impact on outbreaks associated with human food. 

  • Tech-enabled product traceback – Engaging smarter ways to digitize and routinely receive information needed to streamline the traceback process, which are the steps we use to pinpoint the source of contaminated foods during investigations.

    These tactics include obtaining more complete voluntarily provided consumer purchase data to better specify critical traceback information, facilitating and expediting how the FDA receives data, and employing more advanced analytical methods and computational approaches.

    We will work to harmonize our efforts with our federal, state, local and territorial counterparts, as well with industry and others involved in traceback investigations. 
  • Root-cause investigations (RCIs) – Systematizing, expediting and sharing FDA RCIs. The plan focuses on adapting and strengthening protocols and procedures for conducting timely RCIs of foodborne illness outbreaks, standardizing criteria for producing FDA RCI reports, and expediting the release of investigation findings to industry and the public.
  • Strengthen analysis and dissemination of outbreak data – Working with the CDC, the USDA’s FSIS and other partners to identify reoccurring, emerging and persistent strains of pathogens.

    Specifically, we will facilitate improvements to sharing of data with the CDC as well as other regulatory partners to further increase transparency of outbreak investigations, increase public confidence in results, and facilitate improved collaboration on investigation activities. 
  • Operational improvements – Building on performance measures across the FDA’s foods program to better evaluate the timeliness and effectiveness of outbreak and regulatory investigation activities.

    The FDA is committed to using performance and outcome measures to assess progress of this improvement plan by updating stakeholders, posting updates on FDA.gov and through a public webinar in early 2022 to discuss how regulatory partners, industry and others can work together to achieve these goals.

We know that the 21st century has brought new challenges in identifying, investigating and controlling outbreaks of foodborne disease, but it has also brought new tools to meet those challenges.

We also recognize that today’s U.S. food system is large and decentralized, with a broad array of widely distributed products, which we must adapt to in order to help ensure the safety of these products.

That is why we are taking steps through this improvement plan to evolve our outbreak investigations to meet modern-day needs using the most modern-day tools available.

Our investigations must be faster, more streamlined and more effective to identify, pinpoint and remove contaminated food from the market and identify root-cause factors in the food system to prevent similar outbreaks in the future.

Our improvement plan sets out a clear pathway to achieving these important goals. We will continue to do everything we can to protect consumers from unsafe food.

Adding the Outbreak Response Improvement Plan to our arsenal, which includes FSMA and the New Era of Smarter Food Safety, will ultimately prevent illnesses and save lives; and that is what this work is all about for us.”

https://www.fda.gov/news-events/press-announcements/fda-issues-improvement-plan-focused-modernizing-foodborne-illness-outbreak-responses

WHO and Global Fund warn inequalities block progress towards ending AIDS, TB and malaria

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WHO and Global Fund warn inequalities block progress towards ending AIDS, TB and malaria

December 09, 2021: “Inequities have been widely acknowledged as barriers to achieving global and national goals and targets in HIV, TB and malaria programs.

However, the magnitude and extent of underlying health inequalities have remained poorly documented and understood.

Until those inequalities are better identified, and their consequences better understood, it will be hard for programmes to meet people’s real health needs.

Now, for the first time, a new report from the World Health Organization and the Global Fund to Fight AIDS, Tuberculosis and Malaria, systematically assesses the global State of inequality: HIV, tuberculosis and malaria.

The report represents an important step forward in understanding how inequalities are hindering the fight against the three diseases.

Using the latest available global data for 32 health indicators up to 186 countries, it shows that while national averages of HIV, TB and malaria indicators have generally improved in the past decade, the poorest, least educated and rural subgroups tend to remain at a disadvantage across most HIV, TB and malaria indicators.

“Although great strides have been made to expand health services and prevention efforts, we must focus more on reaching the poor, rural and least educated populations who bear the brunt of these diseases,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General.

The report shows, for example, that available data on HIV testing among men reveals a gap of at least 20 percentage points between the poorest and richest households in 27 out of 48 countries with the gap having increased over time.

Many families affected by tuberculosis spend a substantial amount of their income on expenses related to the disease – especially if the household is poor.

Data from 21 countries show that 20-92% of households spend at least a fifth of their income on TB-related costs. For malaria, the poorest, the least educated and rural groups reported lower levels of timely care-seeking for children under age 5 running a fever.

High sex-related inequalities are also quantified in the report. For HIV, in more than half of the countries, males reported higher condom use than females.

HIV testing was substantially higher in women than men in a fifth of countries.

“Pandemics thrive on inequalities and exacerbate inequities: we have learned this with HIV, TB and malaria, and we have seen it again with COVID-19,” said Peter Sands, Executive Director of the Global Fund.

“To tackle the inequities, we must go beyond simple notions of equal access or one-size-fits-all and deliberately create ‘compensating inequalities’ in service provision to focus resources on the most vulnerable.

Our new Strategy turbocharges that approach by placing people and communities front and center of the fight against HIV, TB, and malaria and by putting an even greater focus on removing human rights-related barriers to health services.”

Despite the challenges, the report shows cases where inequalities are low, or where the gaps are narrowing through faster improvements in intervention coverage among disadvantaged population subgroups.

Encouragingly, some countries reported higher insecticide-treated bednet ownership among the poorest households, demonstrating that malaria prevention efforts are targeting and benefiting disadvantaged groups.

The report also illustrates the impact of eliminating inequalities in improving national averages across HIV, TB and malaria.

For example, if countries improved the level of HIV testing of all pregnant women to that of the richest subgroup, the overall level of testing would increase from 40% to 64%.

The percentage of families facing catastrophic costs due to TB would decrease by at least 50% in half of countries (from a current weighted average of 61% to a potential average of 38%).

In the case of malaria, families seeking care for children under 5 years with fever, eliminating economic-related inequalities would mean a 26% improvement in the weighted average across 28 countries.

The report calls for the compilation of more and better data on inequalities. The WHO 2020 global assessment of country data and health information systems found that only half of the 133 study countries included data disaggregation in their published national health statistical reports.

It also calls for regular and dedicated monitoring of inequalities in the fight against HIV, TB and malaria, which should be complemented by other quantitative and qualitative studies.

WHO has developed a package of tools and resources on inequality monitoring and continues to support countries to develop their capacities in this area.

Since 2002, the Global Fund has disbursed more than US$50 billion across more than 155 countries to help communities most in need.

Through its Breaking Down Barriers initiative, the Global Fund has over the last years scaled up programs that remove human-rights related barriers to services – discrimination, gender inequality and violence, criminalization and socioeconomic marginalization.

work, coupled with increased investments in health services for the most under-served, will benefit the national average, bringing countries closer to achieving goals and targets.”

https://www.who.int/news/item/09-12-2021-who-and-global-fund-warn-inequalities-block-progress-towards-ending-aids-tb-and-malaria

Novartis announces positive results of Beovu in diabetic macular edema

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Novartis announces positive results of Beovu in diabetic macular edema

December 9, 2021: “Novartis announced the first interpretable results from year two (week 100) of the Phase III KESTREL study.

KESTREL assessed the safety and efficacy of Beovu® (brolucizumab) 6 mg in patients with visual impairment due to diabetic macular edema (DME). Results from year two confirmed the visual acuity gains, fluid reduction findings and safety profile from year one, while addressing the burden of frequent treatments for DME patients.

Results from year two of KESTREL were consistent with those seen at year one, including maintenance of best-corrected visual acuity (BCVA) and sustained reductions in central subfield thickness (CSFT)

Additionally, numerically fewer Beovu patients had intraocular fluid and/or sub-retinal fluid (IRF/SRF) versus patients treated with aflibercept.

CSFT is a key indicator of fluid in the retina, and fluid is a key marker of disease activity.

More than 40% of Beovu patients were maintained on 12-week dosing intervals, and 70% of patients who completed the first 12-week cycle after loading remained on 12-week dosing through year two, showing the potential for Beovu to offer fluid resolution in more DME patients with fewer injections versus aflibercept.

“With an average age at diagnosis of 48 years, DME primarily affects working-age adults, which means managing their vision, in addition to multiple comorbidities related to diabetes, may result in loss of work productivity and employment instability,” said Dr. David M Brown MD, Director of Research, Retina Consultants of Texas.

“The extended dosing and fluid resolution observed in year two of the KESTREL clinical trial suggest Beovu has the potential to help appropriate patients more conveniently and effectively manage their disease with dosing intervals every 12 weeks after an initial loading phase.”

Further details of year-two findings from the KESTREL trial, along with findings from KITE*, another pivotal Phase III trial of Beovu in DME, will be presented at upcoming medical congresses.

About the KESTREL year two safety results
In KESTREL (NCT03481634), rates of intraocular inflammation (IOI) were 4.2% for Beovu 6 mg, 5.3% for Beovu 3 mg and 1.1% for aflibercept; retinal vasculitis (RV) rates were 0.5% for Beovu 6 mg, 1.6% for Beovu 3 mg and 0% for aflibercept.

Rates of retinal vascular occlusion (RO) were 1.6% for both Beovu 6 mg and 3 mg versus 0.5% for aflibercept. The majority of IOI events were manageable and resolved without any clinical complications.

There were no vascular events reported in year two (weeks 52-100).

No new RV events were reported during year two of KESTREL.

Of the four new RO events reported during year two (two in Beovu 6 mg, one in Beovu 3 mg and one in aflibercept), none were associated with IOI or RV.

Brolucizumab 6 mg is the commercialized dose of Beovu in wet age-related macular degeneration (AMD).

Novartis is committed to bringing Beovu 6 mg to DME patients and has submitted data from KESTREL and KITE (NCT03481660), to global health authorities in H2 2021.

About the KESTREL and KITE clinical trials
KESTREL and KITE are global, randomized, double-masked, Phase III, two-year studies comparing the safety and efficacy of Beovu and aflibercept in the treatment of patients with visual impairment due to DME.

KESTREL and KITE involved 926 total patients in 36 countries. In the loading phase of both trials, patients in the Beovu arms were treated every six weeks for a total of five doses; patients in the aflibercept arms were treated every four weeks for a total of five doses, in line with its label at the start of the studies.

Following the loading phase, patients in the Beovu arms were subsequently treated every 12 weeks, with those demonstrating disease activity moved to dosing every eight weeks for the remainder of the study.

At week 72 of KITE, Beovu patients dosed every 12 weeks could be extended to dosing every 16 weeks, and patients dosed every eight weeks could be extended to every 12 weeks.

About diabetic macular edema (DME)
DME is a common microvascular complication in patients with diabetes that may have a debilitating impact on visual acuity, eventually leading to blindness. DME is the leading cause of blindness in adults in developed countries, affecting 12% of patients with type 1 diabetes and 28% of those with type 2 diabetes.

Consistently high blood sugar levels associated with diabetes can damage small blood vessels in the eye, causing them to leak fluid. This damage leads to an excess of vascular endothelial growth factor (VEGF).

VEGF is a protein that stimulates the growth of blood vessels.

At elevated levels in DME, VEGF stimulates the growth of abnormal, leaky blood vessels.

The resulting accumulation of fluid (known as edema) in the macula can lead to vision impairment or even vision loss.

The macula is the area of the retina responsible for sharp, central vision.

Early symptoms of DME include blurry or wavy central vision and distorted color perception, although the disease can also progress without symptoms at early stages.

About Beovu (brolucizumab) 6 mg
Beovu (brolucizumab, also known as RTH258) 6 mg is approved for the treatment of wet age-related macular degeneration (AMD) in more than 70 countries, including in the US, EU, UK, Japan, Canada and Australia.

Additional trials, which study the effects of brolucizumab in patients with wet AMD, diabetic macular edema (DME), and proliferative diabetic retinopathy (PDR), are currently ongoing.”

https://www.novartis.com/news/media-releases/novartis-announces-positive-results-from-year-two-phase-iii-trial-beovu-diabetic-macular-edema

England Journal of Published results reinforce safety profile of Dupixent

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England Journal of Published results reinforce safety profile of Dupixent

December 08 2021: “The New England Journal of Medicine has published positive results from a pivotal Dupixent® (dupilumab) clinical trial in children aged 6 to 11 years with uncontrolled moderate-to-severe asthma.

These data formed the basis for the FDA approval of Dupixent on October 20, 2021 as an add-on maintenance treatment of patients aged 6 to 11 years with moderate-to-severe asthma characterized by an eosinophilic phenotype or with oral corticosteroid-dependent asthma.

These published results showed Dupixent, when added to standard of care, significantly reduced severe asthma attacks and, within two weeks, rapidly improved lung function in populations with an eosinophilic phenotype, as indicated by elevated blood eosinophils, a certain type of white blood cell, and/or with elevated fractional exhaled nitric oxide (FeNO), an airway biomarker of inflammation that plays a major role in asthma.

“The publication of these Phase 3 results for Dupixent in the New England Journal of Medicine underscore their significance and potential clinical value for younger children with uncontrolled moderate-to-severe asthma,” says Leonard B. Bacharier, M.D., Professor of Pediatrics and Director of the Center for Pediatric Asthma Research, Monroe Carell Jr. Children’s Hospital at Vanderbilt University Medical Center in Nashville, Tennessee, and principal investigator of the trial.

“These data also further our understanding of how addressing type 2 inflammation, a biological process that underlies most cases of childhood asthma, can potentially improve symptoms and outcomes for children suffering from this common chronic disease.”

Asthma is one of the most common chronic diseases in children. Approximately 75,000 children aged 6 to 11 years live with the uncontrolled moderate-to-severe form of the disease in the U.S., and many more worldwide.

Despite treatment with current standard-of-care inhaled corticosteroids and bronchodilators, these children may continue to experience serious symptoms such as coughing, wheezing and difficulty breathing.

They also may require multiple courses of systemic corticosteroids that can carry significant safety risks.

The safety results from the trial were generally consistent with the known safety profile of Dupixent in patients aged 12 years and older with uncontrolled moderate-to-severe asthma, with the addition of helminth infections that were reported in 2.2% of Dupixent patients and 0.7% of placebo patients.

The overall rates of adverse events were 83% for Dupixent and 80% for placebo.

The most common adverse events that were more commonly observed with Dupixent compared to placebo were injection site reactions (18% Dupixent, 13% placebo), viral upper respiratory tract infections (12% Dupixent, 10% placebo) and eosinophilia (6% Dupixent, 1% placebo).

Dupixent is a fully human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways and is not an immunosuppressant.

IL-4 and IL-13 are key and central drivers of the type 2 inflammation that plays a major role in atopic dermatitis, asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP).

The results of this Phase 3 trial were also included in the European regulatory filing, and a decision from the European Medicines Agency in children with uncontrolled severe asthma is expected in Q1 2022.

About the LIBERTY ASTHMA VOYAGE trial

The Phase 3 randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of Dupixent (100 mg for children ≤30 kg or 200 mg for children >30 kg every two weeks) combined with standard-of-care asthma therapy in 408 children aged 6 to 11 years with uncontrolled moderate-to-severe asthma.

The primary endpoint was the annualized rate of severe asthma exacerbations over one year and the key secondary endpoint was the change from baseline in percentage of predicted pre-bronchodilator FEV1 (ppFEV1) at week 12.”

https://www.sanofi.com/en/media-room/press-releases/2021/2021-12-08-23-30-00-2348703

FDA Authorizes New Long-Acting Monoclonal Antibodies for Pre-exposure Prevention of COVID-19 in Certain Individuals

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FDA Authorizes New Long-Acting Monoclonal Antibodies for Pre-exposure Prevention of COVID-19 in Certain Individuals

December 08, 2021: “The U.S. FDA issued an emergency use authorization (EUA) for AstraZeneca’s Evusheld (tixagevimab co-packaged with cilgavimab and administered together) for the pre-exposure prophylaxis (prevention) of COVID-19 in certain adults and pediatric individuals (12 years of age and older weighing at least 40 kilograms [about 88 pounds]). 

The product is only authorized for those individuals who are not currently infected with the SARS-CoV-2 virus and who have not recently been exposed to an individual infected with SARS-CoV-2.

The authorization also requires that individuals either have: 

  • moderate to severely compromised immune systems due to a medical condition or due to taking immunosuppressive medications or treatments and may not mount an adequate immune response to COVID-19 vaccination (examples of such medical conditions or treatments can be found in the fact sheet for health care providers) or;
  • a history of severe adverse reactions to a COVID-19 vaccine and/or component(s) of those vaccines, therefore vaccination with an available COVID-19 vaccine, according to the approved or authorized schedule, is not recommended.

“Vaccines have proven to be the best defense available against COVID-19.

However, there are certain immune compromised individuals who may not mount an adequate immune response to COVID-19 vaccination, or those who have a history of severe adverse reactions to a COVID-19 vaccine and therefore cannot receive one and need an alternative prevention option,” said Patrizia Cavazzoni, M.D., director of the FDA’s Center for Drug Evaluation and Research.

“Today’s action authorizes the use of the combination of two monoclonal antibodies to reduce the risk of developing COVID-19 in these individuals.” 

One dose of Evusheld, administered as two separate consecutive intramuscular injections (one injection per monoclonal antibody, given in immediate succession), may be effective for pre-exposure prevention for six months.

Evusheld is not authorized for individuals for the treatment of COVID-19 or for post-exposure prevention of COVID-19. Patients should talk with their health care provider to determine whether Evusheld is an appropriate pre-exposure prevention option for them.

Pre-exposure prevention with Evusheld is not a substitute for vaccination in individuals for whom COVID-19 vaccination is recommended.

The FDA has approved one vaccine and authorized others to prevent COVID-19 and serious clinical outcomes associated with a COVID-19 infection, including hospitalization and death. The FDA urges the public to get vaccinated if eligible. Learn more about FDA-approved or -authorized COVID-19 vaccines.  

Monoclonal antibodies are laboratory-made proteins that mimic the immune system’s ability to fight off harmful pathogens such as viruses. Tixagevimab and cilgavimab are long-acting monoclonal antibodies that are specifically directed against the spike protein of SARS-CoV-2, designed to block the virus’ attachment and entry into human cells. Tixagevimab and cilgavimab bind to different, non-overlapping sites on the spike protein of the virus. 

The issuance of an EUA is different than an FDA approval. In determining whether to issue an EUA, the FDA evaluates the totality of available scientific evidence and carefully balances any known or potential risks with any known or potential benefits of the product.

Based on the FDA’s review of the totality of the scientific evidence available, the agency has determined that it is reasonable to believe that Evusheld may be effective for use as pre-exposure prevention in certain adults and pediatric individuals (12 years of age and older weighing at least 40 kilograms).

The agency has also determined that the known and potential benefits of Evusheld, when used consistent with the terms and conditions of the authorization, outweigh the known and potential risks of the product.

There are no adequate, approved and available alternatives to Evusheld for the pre-exposure prevention of COVID-19 in the authorized population. 

The primary data supporting this EUA for Evusheld are from PROVENT, a randomized, double-blind, placebo-controlled clinical trial in adults greater than age 59 or with a prespecified chronic medical condition or at increased risk of SARS-CoV-2 infection for other reasons who had not received a COVID-19 vaccine and did not have a history of SARS-CoV-2 infection or test positive for SARS-CoV-2 infection at the start of the trial.

The main outcome measured in the trial was whether a trial participant had a first case of COVID-19 after receiving Evusheld or placebo and before day 183 of the trial.

In this trial, 3,441 people received Evusheld and 1,731 received a placebo.

In the primary analysis, Evusheld recipients saw a 77% reduced risk of developing COVID-19 compared to those who received a placebo, a statistically significant difference.

In additional analyses, the reduction in risk of developing COVID-19 was maintained for Evusheld recipients through six months. The safety and effectiveness of Evusheld for use in the pre-exposure prevention of COVID-19 continue to be evaluated.

Under the EUA, fact sheets that provide important information about using Evusheld in pre-exposure prevention of COVID-19 as authorized must be made available to health care providers and to patients and caregivers.

These fact sheets include dosing instructions, potential side effects and drug interactions. 

Possible side effects of Evusheld include: hypersensitivity reactions (including anaphylaxis), bleeding at the injection site, headache, fatigue and cough.  

Serious cardiac adverse events were infrequent in PROVENT.

However, more trial participants had serious cardiac adverse events (such as myocardial infarction and heart failure) after receiving Evusheld compared to placebo.

These participants all had risk factors for cardiac disease or a history of cardiovascular disease before participating in the clinical trial.

It is not clear if Evusheld caused these cardiac adverse events. 

The FDA is working with sponsors of all currently authorized therapeutics to assess the activity against any global SARS-CoV-2 variant(s) of interest and is committed to communicating with the public as we learn more.

The EUA was issued to AstraZeneca.”

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-new-long-acting-monoclonal-antibodies-pre-exposure

Schistosomiasis and soil-transmitted helminthiases: treating millions of people, despite the pandemic

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Schistosomiasis and soil-transmitted helminthiases: treating millions of people, despite the pandemic

December 08, 2021: “Despite pandemic-related disruptions, a total of 76.9 million people received treatment for schistosomiasis in 2020, representing a global coverage of 31.9%, compared with 105 million treated in 2019 (coverage of 44.8%).

The latest data published by the World Health Organization (WHO) show that 28.6 million fewer people were treated for schistosomiasis (bilharzia) in 2020 than in 2019.

This 27% drop in the number of treatments delivered is largely due to the implementation of COVID-19 measures, including school closures.

“We commend the work of national programmes that were able to conduct treatment by observing COVID-19 safety protocols,” said Dr Amadou Garba-Djirmay, Medical Officer, WHO Department of Control of Neglected Tropical Diseases, who heads the global schistosomiasis elimination programme.

“Most interestingly, more than 90% of all treatment was delivered in countries of WHO’s Africa Region, which carries the greatest global burden of schistosomiasis.”

Treatment targeted at school-aged children decreased from 66.8% in 2019 to 44.9% in 2020.

In 2020, some countries with high numbers of people requiring treatment for schistosomiasis, such as the Democratic Republic of the Congo, Ethiopia, Ghana, and Yemen, did not implement large-scale treatment.

Soil-transmitted helminthiases

The number of school-aged children reached with deworming fell by 25% in 2020 to 342 million, from 455.7 million in 2019.

For preschool-aged children, coverage decreased by 42.9%, from 165.8 million in 2019 to 94.7 million in 2020.

“There was a dramatic decrease from 53.3 million preschool-aged children treated in 2019 to 7.4 million treated in 2020 in WHO’s African Region, and in the Eastern Mediterranean Region from 10 million in 2019 to 0.9 million in 2020,” said Dr Antonio Montresor, Medical Officer, who heads WHO’s global deworming programme.  

This decrease was less severe in other regions. For example, from 90.2 to 75.4 million in the South-East Asia Region and from 10.7 million to 10 million in the Western Pacific Region.

In many countries, deworming programmes were carried out to some extent in schools. This is probably due to the resilience of school programmes, which are supported by teachers, who were able to organize some deworming in class despite repeated closures of schools.

Treating women of reproductive age

Women of reproductive age are particularly vulnerable to the damage caused by soil-transmitted helminth and schistosome infections, which adversely affects not only the health of the women themselves but also that of their newborns.

WHO therefore recommends that countries endemic for schistosomiasis and soil-transmitted helminthiases optimize all contacts of women of reproductive age with health services in order to conduct deworming; for example, with antenatal and postnatal clinics for women, and human papillomavirus vaccination for adolescent girls.

Women and adolescent girls in these countries are particularly vulnerable to the damage caused by both diseases which includes anaemia, micronutrient deficits and female genital schistosomiasis.

The diseases

Schistosomiasis is an acute and chronic parasitic disease caused by trematode worms of the genus Schistosoma.

Infection occurs when larval forms of the parasite – released by freshwater snails – penetrate the skin during contact with infested water.

There are two major forms of schistosomiasis: intestinal and urogenital. Intestinal schistosomiasis usually results in diarrhoea and blood in the stool; enlargement of the liver and of the spleen and portal hypertension are common in advanced cases.

Urogenital schistosomiasis is characterized by the presence of blood in the urine. Chronic infection results in fibrosis of the bladder and ureter that can evolve to hydronephrosis and create conditions for bladder cancer.

In women, urogenital schistosomiasis may cause vaginal bleeding, pain during sexual intercourse and nodules in the vulva – now described as female genital schistosomiasis.

In men, urogenital schistosomiasis can induce disease in the seminal vesicles and prostate.

Soil-transmitted helminthiases are caused by a group of intestinal parasites comprising Ascaris lumbricoides (roundworms), Trichuris trichiura (whipworms), Necator americanus and Ancylostoma duodenale (hookworms) and are transmitted by faecal contamination of soil; they adversely affect nutritional status and impair cognitive processes.

Transmission occurs when eggs are passed in the faeces of infected people. Adult worms live in the intestine where they produce thousands of eggs each day.

In areas that lack adequate sanitation, these eggs contaminate the soil.”

https://www.who.int/news/item/08-12-2021-schistosomiasis-and-soil-transmitted-helminthiases-treating-millions-of-people-despite-the-pandemic

FDA Takes New Steps Aimed at Advancing Development of Individualized Medicines to Treat Genetic Diseases

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FDA Takes New Steps Aimed at Advancing Development of Individualized Medicines to Treat Genetic Diseases

December 07, 2021: “The following quote is attributed to Acting FDA Commissioner Janet Woodcock, M.D.“Progress in individualized medicines provides hope to patients with severely debilitating or life-threatening genetic diseases.

Advances in technology enable targeting a drug to an individual patient’s genes. Single-subject clinical trials—also called ‘N of 1’ trials—focus on evaluating investigational drug products developed for an individual patient.

This field is rapidly evolving, and antisense oligonucleotide drugs are the most advanced in this space.

However, many N of 1 trials are carried out by academic investigators who may not have much experience interacting with the FDA. Earlier this year, the FDA took initial steps to provide draft guidance to investigators carrying out this critical work.

Today, we are issuing additional draft guidance in this area.

Once finalized, this guidance will detail important clinical and production considerations to support applications for these types of clinical trials and drug development programs.

The FDA is hopeful these draft guidances, once finalized, will help promising drugs reach patients in a timely manner.

We are optimistic that the development of these individualized drug products may continue to change the landscape for treating rare diseases, and the FDA is committed to providing resources and guidance to those advancing these technologies to treat patients in need.”

Additional Information

  • Today, the FDA is issuing a draft guidance to provide recommendations for managing the administration of individualized investigational Antisense Oligonucleotide (ASO) drugs in a clinical trial and conducting clinical assessments of the safety and response during administration of the investigational ASO drug.

    The draft guidance describes important clinical considerations for investigational new drug application (IND) submissions to support initial and continued administration, dosing and clinical monitoring of an individual who is eligible to receive an individualized investigational ASO drug.
    The draft guidance is specifically tailored to the unique circumstances involving relatively few (typically one or two) individuals.
  • The FDA is also making available an additional draft guidance that provides recommendations regarding the chemistry, manufacturing and controls information that should be provided in an IND application for certain types of ASO drugs.

    This includes information regarding drug quality (e.g., chemical structure, manufacturing process and critical quality attributes) and manufacturing guidelines.”

https://www.fda.gov/news-events/press-announcements/fda-brief-fda-takes-new-steps-aimed-advancing-development-individualized-medicines-treat-genetic

Roche’s Actemra/RoActemra approved to treat patients with severe COVID-19

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Roche’s Actemra/RoActemra approved to treat patients with severe COVID-19

December 07, 2021: “Roche announced that the European Commission has extended the marketing authorisation for Actemra®/RoActemra® (tocilizumab) to include the treatment of COVID-19 in adults who are receiving systemic corticosteroids and require supplemental oxygen or mechanical ventilation.

This decision comes just hours after the recommendation by the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP), reflecting the urgent need for Actemra/RoActemra as a potential treatment option during the COVID-19 public health emergency.

“Actemra/RoActemra is the second Roche medicine to have received rapid European Commission approval in COVID-19 in recent weeks,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development.

“The totality of evidence shows that Actemra/RoActemra can benefit those suffering with severe COVID-19.

Together with vaccines, other treatments and testing, Actemra/RoActemra forms an important piece of the care puzzle as we confront new challenges of the pandemic in Europe and around the world.”

The decision from the European Commission follows an accelerated assessment by the EMA’s CHMP, which reviewed results from four studies of Actemra/RoActemra in over 5,500 patients with severe or critical COVID-19.

These include the Roche-led phase III COVACTA, EMPACTA and REMDACTA trials, and the University of Oxford’s Randomised Evaluation of COVID-19 Therapy (RECOVERY) study, which was supported by Roche.

Outside of the European Union, Actemra/RoActemra has been provisionally approved in Australia, authorised for emergency use in the United States and Ghana, and recommended by the World Health Organization (WHO) for the treatment of COVID-19.

Roche is working closely with regulatory bodies and other partners around the world on the next steps to bring this medicine to as many people as possible.

Following the recent emergence of the new SARS-CoV-2 variant of concern, Omicron (B.1.1.529), WHO has reported that interleukin 6 receptor blockers, such as Actemra/RoActemra, are expected to still be effective for managing patients with severe COVID-19.

In these exceptional times, we stand together with society, governments, healthcare providers and all those working towards the common goal of overcoming the COVID-19 pandemic.

About Actemra®/RoActemra® (tocilizumab) in COVID-19 clinical trials
Roche has evaluated Actemra/RoActemra in COVID-19 in three phase III randomised studies: COVACTA, EMPACTA and REMDACTA.

COVACTA was a global, randomised, double-blind, placebo-controlled phase III study (COVACTA, NCT04320615), which evaluated the safety and efficacy of intravenous Actemra/RoActemra plus standard of care in adult patients hospitalised with severe COVID-19 pneumonia compared to placebo plus standard of care.

The primary and secondary endpoints included clinical status, mortality, mechanical ventilation and intensive care unit (ICU) variables. Patients were followed for 60 days post-randomisation.

EMPACTA (Evaluating Minority Patients with Actemra) was a phase III, randomised, double-blind, placebo-controlled multicentre study (EMPACTA, NCT04372186) which evaluated the efficacy and safety of Actemra/RoActemra in the treatment of COVID-19 pneumonia among hospitalised patients that are often underrepresented in clinical trials.

The primary endpoint was the cumulative proportion of participants dying or requiring mechanical ventilation by Day 28. Secondary endpoints included: time to clinical failure (defined as the time to death), mechanical ventilation, ICU admission, or withdrawal (whichever occured first); mortality rate by Day 28; and time to hospital discharge or “ready for discharge.”

REMDACTA was a two-armed global phase III, randomised, double-blind, multicentre study (REMDACTA, NCT04409262) to evaluate the efficacy and safety of Actemra/RoActemra plus Veklury® (remdesivir), versus placebo plus Veklury in hospitalised patients with severe COVID-19 pneumonia receiving standard of care.

Veklury is an antiviral medicine that works to stop replication of SARS-CoV-2, the virus that causes COVID-19.

The REMDACTA trial was conducted in collaboration with Gilead Sciences, Inc.

The primary endpoint was improvement in time to hospital discharge by Day 28.

Key secondary endpoints included likelihood of death, likelihood of progression to mechanical ventilation or death, and clinical status. Clinical status was measured by the 7-category ordinal scale, which tracks patients’ clinical status based on the need for intensive care and/or ventilator use, as well as supplemental oxygen requirements.

Patients were followed for 60 days post-randomisation.

There have also been a number of clinical trials with an external third party as the sponsor exploring the efficacy and safety of Actemra/RoActemra for the treatment of patients hospitalised with COVID-19, including the University of Oxford’s RECOVERY study, which was supported by Roche.

RECOVERY was a phase III, randomised trial (NCT04381936), which evaluated whether multiple potential treatments, including Actemra/RoActemra, prevent death in hospitalised adult patients with severe COVID-19.

Results of a prospective meta-analysis of almost 11,000 patients across 27 clinical trials, published by researchers from the World Health Organization in The Journal of the American Medical Association, found that treatment of hospitalised patients with severe or critical COVID-19 with IL-6 receptor blockers, including Actemra/RoActemra, was associated with improved mortality and reduced progression to invasive mechanical ventilation or death compared with usual care or placebo.

The prospective meta-analysis included data on Actemra/RoActemra in COVID-19 from COVACTA, EMPACTA and REMDACTA, along with 16 additional third-party studies.

About Actemra®/RoActemra® (tocilizumab)
Actemra/RoActemra was the first approved anti-IL-6 receptor biologic and is available in both intravenous (IV) and subcutaneous (SC) formulations for the treatment of adult patients with moderate-to-severe active rheumatoid arthritis (RA).

Actemra/RoActemra can be used alone or with methotrexate (MTX) in adult RA patients who are intolerant to, or have failed to respond to, other disease-modifying anti-rheumatic drugs (DMARDs).

In Europe, RoActemra IV and SC are also approved for use in adult patients with severe, active and progressive RA who previously have not been treated with MTX.

Actemra/RoActemra IV and SC are also approved globally for polyarticular juvenile idiopathic arthritis (pJIA) and systemic juvenile idiopathic arthritis (sJIA) in children two years of age and older.

Actemra/RoActemra SC is approved globally for giant cell arteritis (GCA), and Actemra/RoActemra IV is approved for the treatment of chimeric antigen receptor (CAR) T-cell-induced severe or life-threatening cytokine release syndrome (CRS) in people two years of age and older.

Actemra/RoActemra was the first approved treatment for sJIA, GCA and CRS. Actemra SC is now approved in the United States for slowing the rate of decline in pulmonary function in adult patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD).

In addition to the above-mentioned indications, in Japan Actemra IV is also approved for the treatment of Castleman’s disease and adult Still’s disease, and the Actemra SC formulation is approved for Takayasu arteritis.

RoActemra is also approved in Europe for the treatment of COVID-19 in adults who are receiving systemic corticosteroids and require supplemental oxygen or mechanical ventilation.

Actemra/RoActemra is part of a co-development agreement with Chugai Pharmaceutical Co., Ltd and has been approved in Japan since April 2005. Actemra/RoActemra is approved in more than 110 countries worldwide.”

https://www.roche.com/media/releases/med-cor-2021-12-07.htm

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