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Coronavirus (COVID-19) Update: Daily Roundup June 26, 2020

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Coronavirus (COVID-19) Update: Daily Roundup June 26, 2020

June 26, 2020: “The U.S. Food and Drug Administration announced the following actions taken in its ongoing response effort to the COVID-19 pandemic:

  • As part of FDA’s effort to protect consumers, the agency issued a warning letter to one company for selling fraudulent COVID-19 products.

    The company, Curativa Bay Corporation, offers Hypochlorous Skin Spray, a topical hypochlorous acid-containing product for sale in the United States with misleading claims that the product can mitigate, prevent, treat, diagnose, or cure COVID-19 in people.

    Related News: https://lifepronow.com/blog/2020/06/26/coronavirus-covid-19-update-daily-roundup-june-25-2020/

    There are currently no FDA-approved products to prevent or treat COVID-19. Consumers concerned about COVID-19 should consult with their health care provider.
  • FDA updated the templates for laboratories and commercial manufacturers to help facilitate submission of Emergency Use Authorization (EUA) requests for serology tests.

    The updates clarify FDA’s previous recommendations for demonstrating clinical performance and presenting validation data; the updates also provide new recommendations for validation of point-of-care tests.
  • Testing updates:
    • To date, there are 153 currently authorized tests under EUAs; these include 129 molecular tests, 23 antibody tests, and 1 antigen test.

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-daily-roundup-june-26-2020

FDA provides Biologics License Application for Abicipar pegol

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FDA provides Biologics License Application for Abicipar pegol
June 26, 2020: “Allergan, an AbbVie Company, and Molecular Partners Receive Complete Response Letter from FDA on Biologics License Application for Abicipar pegol

Allergan, an AbbVie Company and Molecular Partners, a clinical-stage biotechnology company developing a new class of custom-built protein therapeutics known as DARPin® therapeutics announced that the U.S.FDA has issued a Complete Response Letter to the Biologics License Application for Abicipar pegol, a novel, investigational DARPin® therapy for patients with neovascular (wet) age-related macular degeneration (nAMD).

The letter from the FDA indicates that the rate of intraocular inflammation observed following administration of Abicipar pegol 2mg/0.05 mL results in an unfavorable benefit-risk ratio in the treatment of neovascular (wet) age-related macular degeneration (AMD). 

AbbVie plans to meet with the FDA to discuss their comments and determine next steps.

“We continue to believe in the need for treatment options that provide patients with reliable vision gains and less frequent dosing for the treatment of nAMD,” said Michael R. Robinson, M.D., Vice President, Global Therapeutic Area Head, Ophthalmology, AbbVie. “We are committed to working with the FDA to determine the appropriate next steps for Abicipar pegol.”

The global need for eye health services is projected to increase dramatically in the coming decades, posing a considerable challenge to healthcare systems.

‘Through building a strong, active pipeline, which is focused on significant unmet needs in eye care, AbbVie is committed to developing and delivering sustainable solutions that make a remarkable impact on people’s lives.

DARPin®
DARPin® molecules are derived from naturally occurring binding proteins that consist of repeat sequences with capping structures at each end of the protein. DARPin® molecules have three key properties that have made them an important investigational class of binding protein for researchers: high binding affinity, low molecular weight and customizable applications.

These three properties make DARPin® molecules candidates for a broad range of therapeutic applications and are currently being investigated in therapeutic categories such as ophthalmology, oncology and immuno-oncology.

Allergan and Molecular Partners are committed to advancing patient care through the development of molecules such as Abicipar.

Allergan Eye Care
As a leader in eye care, Allergan has discovered, developed, and delivered some of the most innovative products in the industry for more than 70 years.

Allergan has launched over 125 eye care products and invested billions of dollars in new treatments for the most prevalent eye conditions including glaucoma, ocular surface disease, and retinal diseases such as diabetic macular edema and retinal vein occlusion.

Our eye care pipeline includes over a dozen additional agents for multiple ocular conditions.”

https://news.abbvie.com/news/press-releases/allergan-an-abbvie-company-and-molecular-partners-receive-complete-response-letter-from-fda-on-biologics-license-application-for-abicipar-pegol.htm

Novartis receives positive CHMP opinion for new Xolair® indication to treat chronic rhinosinusitis

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Novartis receives positive CHMP opinion for new Xolair® indication to treat chronic rhinosinusitis

Jun 26, 2020: “Novartis announced that the European Medicines Agency’s  Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the approval of Xolair® (omalizumab) as an add-on therapy with intranasal corticosteroids (INC) for the treatment of adults (18 years and above) with severe chronic rhinosinusitis with nasal polyps (CRSwNP), for whom therapy with INC does not provide adequate disease control.

If approved, omalizumab will be the first treatment for nasal polyps specifically targeting and blocking immunoglobulin E (IgE), which helps to reduce the size of nasal polyps (as defined by Nasal Polyps Score; NPS) and improve symptoms.

The European Commission reviews the CHMP recommendation and usually delivers its final decision within two months.

Related News: Novartis ligelizumab (QGE031) more effective than Xolair®(omalizumab) at inhibiting immunoglobulin E pathway responsible for chronic spontaneous urticaria

https://lifepronow.com/blog/2019/12/19/novartis-provides-update-on-fevipiprant-luster-phase-iii-studies-in-patients-with-uncontrolled-gina-4-5-asthma/

“Patients with chronic rhinosinusitis with nasal polyps suffer from persistent symptoms, such as nasal congestion, facial pain, loss of sense of smell and taste, difficulty breathing and sleep problems, which can significantly impair their quality of life.

Unfortunately, many patients continue to experience symptoms despite standard-of-care, and multiple sinus surgeries,” said Professor Philippe Gevaert, Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium.

“Omalizumab is specifically designed to block immunoglobulin E, which is a key driver in the inflammatory pathway; if approved, it will provide patients, for whom intranasal corticosteroids do not provide adequate disease control, with a treatment option that has been shown to improve both symptoms and quality of life.”

The CHMP positive opinion is based on results from the Phase III POLYP 1 and 2 studies, which were published in the Journal of Allergy and Clinical Immunology in June 2020.

These replicate studies demonstrated that patients treated with omalizumab achieved statistically significant improvements in mean NPS (POLYP 1: -1.08; p<0.0001, POLYP 2: ‑0.90; p=0.014) and daily Nasal Congestion Score (NCS; POLYP 1: -0.89; p=0.0004, POLYP 2: -0.70; p=0.0017) compared to placebo at Week 24 (co-primary endpoints).

All patients received INC (mometasone nasal spray) as background therapy. In both studies, patients treated with omalizumab demonstrated significant improvements in NPS and NCS as early as first assessment (Week 4), compared to placebo1.

Among secondary endpoints, improvements were observed in the Sino-Nasal Outcome Test‑22 (SNOT-22; a health-related quality of life assessment), the University of Pennsylvania Smell Identification Test (UPSIT), the Total Nasal Symptom Score (TNSS) and in sense of smell.

Additionally, reductions in post-nasal drip (posterior rhinorrhea) and runny nose (anterior rhinorrhea) were seen.

In the studies, omalizumab was generally well tolerated and its safety profile was consistent with the previous studies.

“Novartis has a mission to reimagine and advance the care of respiratory patients by developing innovative treatment options that treat the disease, reduce symptoms and improve quality of life,” said Linda Armstrong, MD, Respiratory Development Unit Head, Novartis Pharmaceuticals.

“This CHMP positive opinion builds on the established efficacy and safety profile of omalizumab, which has over 1.3 million patient years of exposure and the potential to become an additional treatment option in the EU for patients with severe chronic rhinosinusitis with nasal polyps.”

Novartis is committed to bringing omalizumab to patients with severe CRSwNP and additional regulatory filings are currently underway in multiple countries, including the US and Switzerland.

Xolair (omalizumab)
Xolair (omalizumab) is the only approved anti-immunoglobulin E (IgE) antibody treatment specifically designed to target and block IgE.

By reducing free IgE, down-regulating high-affinity IgE receptors and limiting mast cell degranulation, Xolair minimizes the release of mediators throughout the allergic inflammatory cascade.”
https://www.novartis.com/news/media-releases/novartis-receives-positive-chmp-opinion-new-xolair-indication-treat-severe-chronic-rhinosinusitis-nasal-polyps

Novartis Cosentyx® gains positive CHMP opinion for pediatric psoriasis

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Novartis Cosentyx® gains positive CHMP opinion for pediatric psoriasis
Jun 26, 2020: “Novartis, a leader in immuno-dermatology and rheumatology, announced the Committee for Medicinal Products for Human Use (CHMP) of the EMA has adopted a positive opinion for Cosentyx® (secukinumab) for the treatment of moderate-to-severe plaque psoriasis in children and adolescents aged 6 to <18 years.

“Psoriasis affects children much deeper than just the skin and can lead to deterioration of quality of life, potentially having a lasting impact on this vulnerable patient population,” said Todd Fox, Global Head of Medical Affairs Immunology, Hepatology and Dermatology at Novartis.

“This is our second positive CHMP opinion for Cosentyx this year alone, following on from recent EC approval in nr-axSpA.

The latest positive opinion is an important step forward in our commitment to reimagining care for children with psoriasis, giving them freedom to enjoy full and active lives.”

Novartis PREVENT data show Cosentyx® for relief in axial spondyloarthritis
Novartis Cosentyx® gains fourth indication in EU with first-in-class approval in axial spondyloarthritis spectrum

The positive CHMP opinion is based on two Phase III international studies in children and adolescents aged 6 to <18 years, one open‑label, two-arm, parallel‑group, multicentre study with moderate-to-severe plaque psoriasis and one randomized, double-blind, placebo and etanercept-controlled study with severe plaque psoriasis.

The studies showed both low-dose (75–150 mg) and high-dose (75–300 mg) of Cosentyx were highly efficacious in rapidly improving skin symptoms and quality of life, with a favorable safety profile up to 52 weeks.

In children with moderate-to-severe plaque psoriasis, the low dose of Cosentyx provided fast and strong skin clearance, with 93% achieving Psoriasis Area Severity Index (PASI) 75 as early as Week 12, 69% achieving PASI 90 at Week 12 and 88% at Week 24, 59.5%% achieving completely clear skin (PASI 100) by Week 12 and 67% by Week 24.

In patients with severe psoriasis, the low dose of Cosentyx ensured sustained skin clearance through Week 52, with PASI 90 achieved in 75% of patients.

Differences in PASI 75 in patients with severe psoriasis treated with Cosentyx were seen as early as Week 4 and in patients with moderate-to-severe psoriasis as early as Week 2.

Half of children with moderate-to-severe plaque psoriasis treated with low dose of Cosentyx reported complete relief from symptom burden of psoriasis on their quality of life by as early as Week 12, as measured by Children’s Dermatology Life Quality Index (CDLQI) 0/1 responses.

In children with severe plaque psoriasis treated with low dose of Cosentyx, 44.7% reported complete relief by Week 12, with 60.6% by Week 52.

Cosentyx safety profile of both the low dose and high dose is comparable and consistent with the established adult psoriasis indication. No new safety signals were observed in children.

Phase III data in moderate-to-severe plaque psoriasis were presented as a late breaking abstract at the 2020 American Academy of Dermatology Virtual Meeting Experience (AAD VMX) in June 2020.”

https://www.novartis.com/news/media-releases/novartis-cosentyx-gains-positive-chmp-opinion-pediatric-psoriasis-reinforcing-established-efficacy-and-safety-profile

What is Phase-I Clinical Trial?

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What is Phase-I Clinical Trial?
“As we all know in clinical trials are mainly conducted in five phases viz. Phase I, Phase II, Phase III and Phase IV. 
Phase I in clinical trials primarily aim to determine the safety, tolerability and pharmacokinetics (PK) of investigational product.

The Phase I trials are normally conducted in the following sequence: single ascending dose, multiple ascending doses, an examination of the preliminary effect of the food on exposure, and any potential drug-drug interaction, with assessments to determine the effect of gender, age, bioavailability and bioequivalence performed as required.

Formerly Phase I trials were referred to as “first-in-man studies” but the field generally moved to the gender-neutral language phrase “first-in-humans” in the 1990s; These trials are the first stage of testing in human subjects.

During phase I of a clinical trial, investigators spend several months looking at the effects of the medication on about 20 to 80 people who have no underlying health conditions.

In addition to evaluating safety and ideal dosage, investigators also look at the best way to administer the drug, such as orally, intravenously, or topically.

According to the FDA, approximately 70 percent Trusted Source of medications move on to phase II.

Phase I trials usually include dose-ranging, also called dose escalation studies, so that the best and safest dose can be found and to discover the point at which a compound is extremely poisonous to administer.

The tested range of doses will habitually be a fraction[quantify] of the dose that caused harm in animal testing.

Phase I trials can be further divided into Single ascending dose (Phase Ia) and Multiple ascending doses (Phase Ib)

Single ascending dose (Phase Ia)

A small group of subjects/healthy volunteers receive a single dose of study drug while being observed and tested for a period of time to confirm safety and characterize the PK of the study drug, where safety and PK assessments are done for a predefined time.

How Single Ascending dose studies (SAD) are designed for the Clinical Trials 

The SAD study follows the following steps –

Initially a small number of healthy volunteers (usually n~3 to 5) are dosed with one particular dose (x1)

If there are no adverse events and the PK data are roughly in line with predicted safe values: the dose (x2) is escalated, either within the same group or a further group of healthy subjects who are then given the higher dose (x2).

Dose escalation continues till the maximum dose was attained as per protocol unless a predefined maximum exposure is reached or unacceptable side effects were apparent.

Dose escalation proceeds according to the protocol assuming strict safety and PK criteria are met.

If unacceptable toxicity is observed in any of the three participants, an additional number of volunteers, are treated at the same dose

TIt is maintained until pre-calculated thresholds of pharmacokinetic efficacy are achieved, or unacceptable side effects begin to occur (where the medication is claimed to have exceeded the maximum tolerated dosage [MTD])

If anIf there is an additional unacceptable toxicity, the dose escalation will be terminated and this dose, or perhaps the previous dose, will be considered as the maximum tolerated dose.

This particular design assumes that when approximately 1/3 of the subjects report unacceptable toxicity, the maximally tolerated dose occurs. There are variations to this design but the majority are similar.

In addition to the above, the dose escalation may be discontinued (or proceeded more cautiously than planned) if there is evidence of a supra-proportional dose-to-exposure relationship, i.e. exposures at higher dose levels become difficult to predict.

Single ascending dose (Phase Ia)

A small group of subjects/healthy volunteers receive a single dose of study drug while being observed and tested for a period of time to confirm safety and characterize the Pk of the study drug, where safety and PK assessments are done for a predefined time.

How Single Ascending dose studies (SAD) are designed for Clinical Trials 

The SAD study follows the below steps –

Initially a small number of healthy volunteers (usually n~3 to 5) are dosed with one particular dose (x1)

If there are no adverse events and the PK data are roughly in line with predicted safe values: the dose (x2) is escalated, either within the same group or a further group of healthy subjects who are then given the higher dose (x2).

Dose escalation continues until the maximum dose was attained as per protocol unless a predefined maximum exposure is reached or unacceptable side effects were apparent.

Dose escalation proceeds according to the protocol assuming strict safety and PK criteria are met.

If unacceptable toxicity is observed in any of the three participants, an additional number of volunteers, are treated at the same dose

This is continued until pre-calculated pharmacokinetic safety levels are reached, or intolerable side effects start showing up (at which point the drug is said to have reached the maximum tolerated dose [MTD])

If an additional unacceptable toxicity is observed, then the dose escalation is terminated and that dose, or perhaps the previous dose, is considered as the maximum tolerated dose.

This particular design assumes that the maximally tolerated dose occurs when approximately 1/3rd of the subjects report unacceptable toxicity. Variations to this design do exist, but most are similar ones.

Apart from the above, the dose escalation can be discontinued (or proceed more cautiously than planned) if there is evidence of a supra-proportional relationship between dose and exposure, i.e. exposures at higher dose levels become difficult to predict. Usually, these make the Phase 1a studies.

https://www.linkedin.com/pulse/single-ascending-dose-multiple-amlan-kumar-pradhan/

Benefits of Single Ascending dose study  

Benefits of SAD studies mainly include sequential groups in a parallel design for the maximum exposure or have a crossover design to provide more information on dose linearity.

Studies are regularly placebo controlled to determine whether effects observed are due to the study drug or environmental conditions, and are often conducted in a single (subject) blinded manner to allow informed decision on dose escalation, with safety and PK data being accessible for investigator review. 

Multiple ascending dose (Phase Ib)

Multiple ascending dose studies investigate the pharmacokinetics and pharmacodynamics (PK and PD) of multiple doses of the drug, looking at safety and tolerability. (in nutshell Mad studies check for safety/tolerability and PK/PD)

How Multiple Ascending dose studies (SAD) are designed for Clinical Trials 

The MAD study follows the below steps –       

The dose levels and dosing intervals (i.e., time between successive doses) are selected based on the prediction from the single dose study data (safe dose/MTD).

The dose is consequently escalated for further groups, up to a predetermined level.

Dose levels and dosing frequency are chosen in order to achieve therapeutic drug levels within human systemic (blood) circulation which is maintained at steady state for several days to allow appropriate safety parameters to be monitored.

This involves enrolment of healthy volunteers or patients depending on the results from the SAD studies or can be an extension of SAD study as well.

A group of healthy volunteer/patients receive multiple low doses of the drug, while samples (of blood and other fluids) are collected at various time points and analysed to obtain information on ‘how drug is processed within the body.”

Blood samples are collected and analysed from study participants to allow the determination of PK profiles and a improved understanding of how the drug is processed by the body; with multiple dosing, a important part of the PK analysis is to identify if accumulation of the drug occurs.

Benefits of Multiple Ascending dose study 

Most recently, to minimize the costs of product production and time to market, the above designs have been merged into single modular protocols that provide sufficient dosing periods that allow for analysis of safety and/or PK results before continuation of the trial, i.e., we may have SAD and MAD in the same research design. Sometimes it also includes an assessment of food effect. Usually, that is the practice being followed in clinical trials now.

conclusion

Apart from identifying the pharmacokinetic and pharmacodynamics natures of the trial molecule, the SAD and MAD study designs also highlight on safety and tolerability of the subjects participating in the Clinical Trials.

They also help in identifying the intolerable side effects of any drug molecule at a particular dose level and define maximum tolerated dose.”

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/what-clinical-trials-are/phases-of-clinical-trials#phase1

FDA approves pembrolizumab for cutaneous squamous cell carcinoma

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FDA approves pembrolizumab for cutaneous squamous cell carcinoma
June 24, 2020: The Food and Drug Administration approved pembrolizumab (KEYTRUDA) for patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation.

Efficacy was investigated in KEYNOTE-629 (NCT03284424), a multicenter, multi-cohort, non-randomized, open-label trial.

The trial excluded patients who had previously received therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody and those with autoimmune disease or a medical condition that required immunosuppression.

Patients received pembrolizumab 200 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or a maximum of 24 months.

Assessment of tumor status was performed every 6 weeks during the first year and every 9 weeks during the second year.

The major efficacy outcome measures were objective response rate (ORR) and response duration as assessed by blinded independent central review according to RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The ORR was 34% (95% CI: 24, 44) and median response duration was not reached (range: 2.7, 13.1+ months).

Related News: FDA Approves Merck’s KEYTRUDA® (pembrolizumab) for Use at an Additional Recommended Dose of 400 mg Every Six Weeks for All Approved Adult Indications

Merck’s Checkpoint Inhibitor Keytruda (pembrolizumab) Hits Another Mark in Breast Cancer
KEYTRUDA® plus LENVIMA® Combination Demonstrated Meaningful Tumor Response Rates in Unresectable Hepatocellular Carcinoma and Advanced Renal Cell Carcinoma

Adverse reactions occurring in patients with cSCC enrolled in KEYNOTE-629 were similar to those occurring in patients who received pembrolizumab as a single agent in other clinical trials.

The most common adverse reactions to pembrolizumab are fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain.

Pembrolizumab is associated with immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions.

Efficacy and safety of pembrolizumab using a dosage of 400 mg every 6 weeks for cSCC was primarily based on the modeling of dose/exposure efficacy and safety relationships and observed pharmacokinetic data in patients with melanoma.

The recommended pembrolizumab doses for cSCC are 200 mg every 3 weeks or 400 mg every 6 weeks.

View full prescribing information for KEYTRUDA.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email [email protected].

For information on the COVID-19 pandemic, see the following resources:

Coronavirus (COVID-19) Update: Daily Roundup June 25, 2020

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Coronavirus (COVID-19) Update: Daily Roundup June 25, 2020

June 25, 2020: “The U.S. Food and Drug Administration announced the following actions taken in its ongoing response effort to the COVID-19 pandemic:

  • A new FDA Voices, titled Partnering with the European Union and Global Regulators on COVID-19, explains how the FDA and the European Union, including the latter’s European Medicines Agency, have long leveraged each other’s expertise and experience to promote the safety, effectiveness, and quality of medical products to advance the health of our respective citizens.

    Now, our work, built together over more than a decade, has paved the way for a multitude of critical collaborations on many scientific and regulatory fronts as part of our response to the global COVID-19 public health crisis.
  • FDA’s list of Emergency Use Authorizations (EUAs) for Ventilators and Ventilator Accessories has been updated, adding the AustinP51 (resuscitator) to Appendix B of the ventilator EUA.

    The AustinP51 is a portable emergency-use resuscitator designed to provide either continuous or intermittent ventilatory support for patients requiring mechanical ventilation through volume control.

    The AustinP51 emergency-use system (EURS) is for use by professionals qualified and trained in the use of general ventilation equipment, or who are specifically trained on the AustinP51 system.

    This EURS is intended for use in healthcare settings to treat adults during the COVID-19 pandemic.

    Related News https://lifepronow.com/blog/2020/06/26/coronavirus-covid-19-update-daily-roundup-june-24-2020/
  • Testing updates:
    • To date, there are 150 currently-authorized tests under EUAs; these include 126 molecular tests, 23 antibody tests, and 1 antigen test.

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-daily-roundup-june-25-2020

Novartis Resolves Legacy FCPA Investigations

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Novartis Resolves Legacy FCPA Investigations
 June 25, 2020: “Novartis has reached settlements with the US Department of Justice (DOJ) and the US Securities and Exchange Commission (SEC) resolving all Foreign Corrupt Practices Act (FCPA) investigations into historical conduct by the Company and its subsidiaries.

As part of the settlements, Novartis and certain of its current and former subsidiaries will pay USD 233.9 million to the DOJ and USD 112.8 million to the SEC.

To resolve the DOJ investigation, Novartis Hellas S.A.C.I. has entered into a deferred prosecution agreement (“Novartis Hellas DPA”) pertaining to inappropriate economic benefits provided to Greek healthcare professionals from 2012 to 2015 in connection with the ophthalmology product Lucentis.

The Novartis Hellas DPA also covers books and records issues pertaining to the Lucentis conduct and to conduct related to a 2009 epidemiological study.

Today’s resolutions contain no allegations relating to any bribery of Greek politicians, which is consistent with what Novartis found in its own internal investigation.

With today’s agreements, all outstanding FCPA investigations into Novartis are now closed.

Alcon Pte Ltd, a former Novartis subsidiary, has entered into a separate deferred prosecution agreement with the DOJ (“Alcon DPA”) pertaining to inappropriate economic benefits provided to Vietnamese healthcare professionals and books and records violations from 2011 to 2014 in Vietnam. This conduct related to a consultancy program run by a distributor in Vietnam.

To resolve the SEC investigation, Novartis AG has reached an agreement pertaining to internal controls and books and records violations in Greece, Vietnam and South Korea.

The violations in Greece pertain to the Lucentis-related conduct covered in the Novartis Hellas DPA as well as controls issues with Novartis Hellas post-approval studies identified by internal review in 2012 and resolved by 2013. In Vietnam, the violations relate to the activities involving an Alcon distributor that are the subject of the Alcon DPA.

And in South Korea, the violations relate to conduct for which Novartis has already taken responsibility in South Korea, where the Company is in the final stages of resolving these issues with the local authorities.

Finally, the SEC agreement addresses certain internal controls and books and records issues related to Alcon China’s placement of surgical devices.

As recognized by the DOJ and SEC, Novartis and its subsidiaries, current and former, fully cooperated with these investigations and have already implemented appropriate remedial measures.

Shannon Thyme Klinger, Group General Counsel of Novartis, said: “We are pleased that all outstanding FCPA investigations into the company are now closed.

Today’s settlements represent another milestone in our commitment to resolving legacy compliance issues and ensuring that Novartis truly lives its values.

We have implemented and continue to implement initiatives to ensure we operate with the same high ethical values wherever we do business, and we remain focused on building trust with society.”

Since the time periods at issue in these legacy investigations, Novartis has made significant changes to enhance its approach to ethics, risk, and compliance.

The Company has strengthened its governance by adopting principles-based compliance policies, reinforced its speak-up culture so associates can more effectively raise concerns about potential misconduct, and combined its risk management and compliance functions to enable more effective risk management and mitigation efforts.
https://www.novartis.com/news/media-releases/novartis-resolves-legacy-fcpa-investigations

Roche’s Rozlytrek recommended by NICE for cancer

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Roche’s Rozlytrek recommended by NICE for cancer
June 25, 2020: “Entrectinib (Rozlytrek, Roche), a revolutionary treatment for a range of cancers, is the second histology independent drug to be recommended by NICE for use on the Cancer Drugs Fund (CDF).

As a histology independent treatment, entrectinib targets all solid tumours that have a certain genetic mutation (a neurotrophic tyrosine receptor kinase (NTRK) gene fusion), regardless of where the cancer originated in the body.

This is particularly beneficial to patients with some rare types of cancer where the treatments are currently limited.

The final draft decision is set to benefit adults and children 12 years and older, with advanced NTRK fusion-positive solid tumours, who have no satisfactory treatment options. Eligible patients will have access to entrectinib through the CDF once the marketing authorisation has been granted. 

Meindert Boysen, deputy chief executive and director of the centre for health technology evaluation at NICE, said: “Today’s decision is another positive step forward for cancer care driven by genomics. Treatments like entrectinib, have the potential to revolutionise how we treat cancers by targeting a genetic mutation that activates tumour growth irrespective of the solid tumour’s location.

“While the evidence suggests that solid tumours with NTRK gene fusions shrink in response to entrectinib, further trial data is needed. We are therefore pleased that, because of the joint working between NICE, NHS England and NHS Improvement and the company, adults and children 12 years and older will be able to access entrectinib on the CDF while more data is collected to address any clinical uncertainties.”

Professor Peter Johnson, NHS clinical director for cancer said: “As well as helping cancer patients to continue to get essential care during the coronavirus pandemic, the NHS has been working to bring new treatments onto the front line of patient care. 

“This is the latest deal that the NHS has struck, working together with Roche, to help hundreds of cancer patients every year who will now be able to have this important molecular targeted treatment.”

Between 600–700 people have solid tumours with NTRK gene fusions. A proportion of these people, who have no satisfactory treatment options, will be eligible for treatment within the first year that it is available on the CDF.

Earlier this year, NICE also recommended histology independent treatment, larotrectinib (Vitrakvi, Bayer), for a similar patient group on the CDF.”

https://www.nice.org.uk/news/article/cancer-patients-to-benefit-from-new-histology-independent-treatment

Kymab wins Supreme Court case against Regeneron

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Kymab wins Supreme Court case against Regeneron

June 24, 2020:”Kymab, a clinical-stage biopharmaceutical company developing fully human monoclonal antibody therapeutics, is pleased to announce that the Supreme Court of the United Kingdom has held that all of the claims of two patents (European Patents EP(UK) 1 360 287 and EP(UK) 2 264 163, the ‘Murphy patents’) owned by Regeneron Pharmaceuticals Inc that were asserted against Kymab are invalid.

The Court’s decision upholds the February 2016 decision of the High Court trial judge, Mr. Justice Henry Carr to revoke the claims and reverses the Appeal Court’s determination that they were valid. 

A five-member panel of the Supreme Court heard arguments on the 11th and 12th of February 2020 and announced their decision today, 24th of June 2020. It was held that the relevant claims of the Murphy patents were invalid for insufficiency because they did not enable the ordinary skilled person to work the claimed invention across the breadth of the claims, in line with established jurisprudence of the UK courts and European Patent Office.

The Supreme Court noted that Kymab’s ability to create transgenic mice with the entire human antibody variable region depended upon Kymab’s own inventions made separately after the priority date of the Murphy patents.

“We are grateful that the Court has recognized the shortcomings of the Regeneron patents and reinforced the established law that requires that an invention is adequately enabled across its scope”, said Simon Sturge, Chief Executive Officer of Kymab. He added, “Kymab’s IntelliSelect® platforms continue to generate best‑in‑class, fully human monoclonal antibodies, underpinned by our extensive IP estate.”

“This case raised fundamentally important questions of patent law relevant to a wide variety of innovative life science companies in the UK” said Dr. Penny Gilbert, partner at Powell Gilbert LLP.

“The Supreme Court has confirmed that patents should not be available for inventions that are not adequately enabled. Kymab has shown tremendous resilience in defending this case since Regeneron commenced proceedings in September 2013 and we are pleased to have helped them achieve this great result.”

The Murphy patents sought to cover genetically modified mice containing chimeric human-mouse antibody genes and the human antibodies made using such mice.

The European Patent Office had previously upheld the patents but had not considered evidence that was available to the UK Courts.

Counterparts of the Murphy patents have also been litigated by third parties in the US where an equivalent Murphy patent was found to be invalid. 

Kymab’s patent estate provides protection in the United States, Europe, Japan and other globally important commercial markets for human antibody therapeutics.

Kymab’s patents cover human antibodies produced using transgenic platforms that employ chimeric human-mouse antibody genes. In September 2019 and January 2020, Regeneron filed requests at the US Patent Office’s PTAB (Patent Trial & Appeal Board) seeking Inter Partes Review (IPR) proceedings against 5 of Kymab’s US patents.

The PTAB rejected all 5 petitions filed by Regeneron leaving each patent and their claims in full force in the US. Regeneron filed oppositions against Kymab’s Japanese patents, but these patents were upheld in unappealable decisions by the Japanese Patent Office.

In August 2019 the Australian Patent Office (IP Australia) rejected on all grounds an opposition by Regeneron against Kymab’s patent protecting therapeutic antibodies produced from transgenic mouse platforms.

Regeneron appealed to the Australian Federal Court, but in May 2020 Regeneron agreed to dis­continue its appeal and Kymab’s Australian patent is now upheld and in force.”
https://www.kymab.com/news-and-events/news/2020/jun/24/kymab-wins-supreme-court-case-against-regeneron/

Breztri Aerosphere reduced rate of COPD exacerbations in Phase III ETHOS trial

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Breztri Aerosphere reduced rate of COPD exacerbations in Phase III ETHOS trial
June 24, 2020: “AstraZeneca’s triple-combination therapy Breztri Aerosphere (budesonide/glycopyrronium/formoterol fumarate) significantly cut the rate of moderate or severe exacerbations compared with two dual-combination therapies in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).

Full results from the positive Phase III ETHOS trial showed AstraZeneca’s triple-combination therapy Breztri Aerosphere (budesonide/glycopyrronium/formoterol fumarate) demonstrated a statistically significant reduction in the rate of moderate or severe exacerbations compared with two dual-combination therapies in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).

Compared with Bevespi Aerosphere (glycopyrronium/formoterol fumarate), Breztri Aerosphere achieved a 24% reduction (p<0.001) in exacerbations. Breztri Aerosphere achieved a 13% reduction (p=0.003) compared with PT009 (budesonide/formoterol fumarate).

The dual-combination therapies used as comparators in the trial represent recommended therapeutic classes for the treatment of COPD.

In a key secondary endpoint, Breztri Aerosphere showed a 46% reduction in the risk of all-cause mortality compared with Bevespi Aerosphere (unadjusted p=0.01).

The results were published in the New England Journal of Medicine and simultaneously presented at the American Thoracic Society virtual Scientific Symposium, Clinical Trial Results in Pulmonary Medicine.3 AstraZeneca will continue to review these data with health authorities.

Klaus Rabe, Professor of Pulmonary Medicine at the University of Kiel, Director of the Department of Pneumology at Clinic Grosshansdorf, Germany, and Lead Investigator of the ETHOS trial, said: “The Phase III ETHOS trial results are important and demonstrate the benefit of Breztri Aerosphere in reducing the rate of exacerbations in this progressive disease. The findings also show that reducing risk of all-cause mortality is achievable and could transform treatment goals in chronic obstructive pulmonary disease.”

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “Chronic obstructive pulmonary disease is the third leading cause of death worldwide and exacerbations can contribute to an increase in mortality in these patients.

The results of the Phase III ETHOS trial support the strong clinical profile of Breztri Aerosphere in reducing exacerbation rates compared with dual-combination therapies.

We are excited to have the data on all-cause mortality, which is a key consideration for COPD management.”

The safety and tolerability of Breztri Aerosphere were consistent with the known profiles of the dual comparators. 

In the trial, the most frequently reported adverse events were nasopharyngitis, COPD and upper respiratory tract infection. The incidence of confirmed pneumonia was 4.2% with Breztri Aerosphere, 2.3% with Bevespi Aerosphere and 4.5% with PT009.

These results are based on Breztri Aerosphere at the standard dose of budesonide (budesonide/glycopyrronium/formoterol fumarate 320/14.4/9.6mcg), an inhaled corticosteroid (ICS). In the trial, Breztri Aerosphere at half the dose of budesonide (budesonide/glycopyrronium/formoterol fumarate 160/14.4/9.6mcg) also demonstrated a statistically significant reduction in the rate of moderate or severe exacerbations compared with Bevespi Aerosphere (glycopyrronium/formoterol fumarate 14.4/9.6mcg) and PT009 (budesonide/formoterol fumarate 320/9.6mcg).

Breztri Aerosphere is approved in Japan and China for patients with COPD. It is under regulatory review in the US and EU.”
https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/breztri-aerosphere-significantly-reduced-rate-of-moderate-or-severe-copd-exacerbations-in-phase-iii-ethos-trial.html

Coronavirus (COVID-19) Update: Daily Roundup June 24, 2020

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Coronavirus (COVID-19) Update: Daily Roundup June 24, 2020

June 24, 2020: “The U.S. Food and Drug Administration announced the following actions taken in its ongoing response effort to the COVID-19 pandemic:

  • Today, FDA launched the first “FDA Insight” podcast, featuring FDA Commissioner Stephen Hahn, M.D., and FDA Deputy Commissioner for Medical and Scientific Affairs Anand Shah, M.D., discussing FDA’s COVID-19 efforts, including the drug development process for a COVID-19 treatment.

    Future FDA Insight podcasts will feature Hahn, Shah, and other FDA leaders’ insights into issues facing the agency — including the COVID-19 pandemic and other emerging topics.
  • FDA Commissioner Stephen Hahn, M.D., spoke at the German Marshall Fund’s Brussels ForumExternal Link Disclaimer 2020.

    This 15th edition of the forum, live-streamed/posted on YouTubeExternal Link Disclaimer, featured a 25-minute conversation with Dr. Hahn, moderated by Axios Health Care Editor Sam Baker.
  • Today, U.S. Secretary of Agriculture Sonny Perdue and FDA Commissioner Stephen Hahn, M.D., issued the following joint USDA-FDA statement regarding food export restrictions pertaining to COVID-19:The United States understands the concerns of consumers here domestically and around the world who want to know that producers, processors and regulators are taking every necessary precaution to prioritize food safety especially during these challenging times.

    However, efforts by some countries to restrict global food exports related to COVID-19 transmission are not consistent with the known science of transmission.

    There is no evidence that people can contract COVID-19 from food or from food packaging. The U.S. food safety system, overseen by our agencies, is the global leader in ensuring the safety of our food products, including product for export.
  • Testing updates:

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-daily-roundup-june-24-2020

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