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One Health is critical to addressing zoonotic public health threats and environmental issues

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March 21, 2022: “The complex links between human, animal and environmental health require coordinated multidisciplinary and multipronged collaboration to address the threats from zoonotic diseases, and the global public health community needs to act decisively now.

This can be done through One Health – an integrated, unifying approach that aims to sustainably balance and optimize the health of people, animals and ecosystems – which is key to addressing zoonotic public health threats, environmental issues and neglected tropical diseases (NTDs).

This is one of the main messages that surfaced from a webinar hosted by the World Health Organization (WHO) last Wednesday, with more than 800 people following live the discussions on Zoom.

The webinar formally launched the One Health companion document to the NTD road map for 2021-2030.

In their comments, both Bernadette Abela-Ridder, Veterinary epidemiologist, WHO Department of Control of Neglected Tropical Diseases, and Wendy Harrison, Chief Executive Officer, Schistosomiasis Control Initiative Foundation, commented on One Health and the objectives of the document.

Ending the neglect to attain the sustainable development goals.  One health: approach for action against neglected tropical diseases 20212030 aims to support the health community to achieve the 2030 targets through transdisciplinary, cross-cutting approaches that include:

  • building networks and increasing communication within and among sectors;
  • finding common ground to coordinate and identifying opportunities to get started;
  • recognizing that integration can take place at different levels, and will not be appropriate for everything;
  • distributing resources equitably, and investing in prevention at the source; and
  • leading change, while recognizing and encouraging individual contributions.


Unlocking political will to drive progress

Onyeka Erobu, Senior Health Advisor to Yvonne Aki-Sawyerr OBE, Mayor of Freetown, Sierra Leone

Onyeka shared how Freetown prioritized NTDs and the challenges they encountered applying One Health to address endemic zoonotic diseases.

Almost every district in Sierra Leone is endemic for at least two NTDs and the burden is high. Considering the Ebola outbreak in Sierra Leone during 2014-2016, One Health is not a new concept and many lessons have been learnt in how it can be applied.

Political commitment led to the establishment of the National One Health Platform in 2019, followed by the development of the National Strategic Plan for One Health.

Freetown is now focusing on integrated approaches for action against NTDs, demonstrating their impact beyond the health sector, and emphasizing the links between human, animal and environmental sectors for development in accordance with the Sustainable Development Goals.

For example, Freetown’s newly established multisectoral rabies control strategy goes beyond rabies interventions to include deworming, treatment of skin diseases and other animal health issues in dogs.

One Health financing to support sustainable change

Franck Berthe, Senior Livestock Specialist, World Bank, Washington DC, USA

Franck emphasized that NTDs and affected, marginalized communities are at the heart of the World Bank’s goals to end extreme poverty within a generation and boost shared prosperity.

He referred to the example of the Onchocerciasis Control Programme, funded by the World Bank in the early 1970s, which illustrated how financing a disease programme can benefit health and the environment.

He said that using a One Health approach can increase benefits tremendously compared to their costs, but sectors often compete for financing instead of having shared financing as a national investment.

In addition, funding can be diverted by outbreaks and events, leaving NTDs in a cycle of panic and neglect as attention is directed to other issues.

Franck added that to support sustainable change, the World Bank has included One Health in the 20th replenishment process of the International Development Association.

Environmental interventions for One Health

Lee Ching Ng, Director, National Environment Agency’s Environmental Health Institute, Singapore

Lee Ching explained how environmental interventions are used to mitigate the risks of vector-borne diseases in Singapore, where improved living conditions, piped drinking-water and waste management have significantly reduced the incidence of dengue and malaria.

However, environmental risk factors for dengue infections have persisted and are largely due to standing water sources such as containers (particularly in older buildings), while construction sites and vegetation, combined with a humid climate, offer perfect breeding grounds for mosquitoes.

In Singapore, these risks are being addressed through intersectoral collaboration to implement biological controls; and alert systems to detect changes in vector numbers.

Engaging the veterinary sector to strengthen surveillance

Harena Rasamoelina, Coordinator, SEGA One Health Network, Indian Ocean Commission, Mauritius

Harena discussed the ways in which the SEGA One Health Network supports disease surveillance in a network of countries of the Indian Ocean Commission comprising the Comoros, Madagascar, Mauritius, Reunion and the Seychelles.

This has enabled the establishment of a surveillance and response mechanism across sectors where health data are shared to strengthen capacity.

The network supports efforts to control and eliminate several NTDs, including rabies, taeniasis and cysticercosis, and arboviral diseases such as dengue and chikungunya. Other NTDs are included at the request of members forming part of the Indian Ocean Commission.

Harena highlighted the benefits of One Health approaches and the importance of involving communities.”

https://www.who.int/news/item/21-03-2022-one-health-is-critical-to-addressing-zoonotic-public-health-threats-and-environmental-issues

Sanofi moves forward with EUROAPI listing on Euronext Paris

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March 18 2022. Today marks a major milestone for EUROAPI, a leading European company dedicated to the development, production and marketing of active pharmaceutical ingredients* (API), as Sanofi’s Board of Directors unanimously proposed, on March 17th, to submit to its shareholders the distribution of circa 58% of the share capital of EUROAPI.

In addition to the previously proposed €3.33 cash dividend per Sanofi share, this additional extraordinary dividend, exclusively in kind, is subject to shareholders approval at Sanofi’s May 3, 2022 Ordinary and Extraordinary Shareholders’ Meeting.

If approved, the distribution will take place shortly after the listing of EUROAPI’s shares on the regulated market of Euronext Paris, subject to the approval of the French Autorité des Marchés Financiers (AMF) on EUROAPI’s French prospectus, which will be made available to the public ahead of Sanofi’s Shareholders’ Meeting.

Through this transaction, Sanofi is giving its shareholders the opportunity to take part in the success of a leading player in the API market with strong ambitions to become a global champion on a growing and dynamic market, and due to be listed on the regulated market of Euronext Paris.

In connection with the proposed spin-off, French Tech Souveraineté has agreed to purchase
12% in EUROAPI shares from Sanofi for up to €150 million, with the acquisition price to be determined based upon the thirty day volume weighted average trading price (“VWAP”) of EUROAPI’s shares on Euronext Paris, starting on the first day of trading.

As a result, French Tech Souveraineté will become a long-term reference shareholder of EUROAPI and will be represented by two non-executive members on EUROAPI’s Board of Directors, including Benjamin Paternot and another member to be determined.

French Tech Souveraineté’s investment is subject to approval of the spin-off by Sanofi’s shareholders and other customary conditions.

Post transaction, Sanofi confirms that it will hold circa 30% of the share capital and voting rights of EUROAPI and will remain a long-term strategic partner, supporting EUROAPI’s growth ambitions as an independent company over the coming years.

In addition to its highly diversified customer base of approximately 530 customers, EUROAPI benefits from a strong and long-term customer relationship with Sanofi, which represented nearly half of EUROAPI’s revenues in 2021.

In line with its “Play to Win” strategy aiming at simplifying its operations, Sanofi announced in February 2020 its ambition to create a new world leader in APIs to secure significant manufacturing and supply capacities that are critical for patients in Europe and beyond, in a context of increasing shortage of medicines essential to patient care.

In 2021, Sanofi announced several critical steps in this journey with the unveiling of the creation of EUROAPI and the appointment of Karl Rotthier as its CEO in January, the appointment of Viviane Monges as Chair of the Supervisory Board in July and the finalization of the carve-out in December 2021.

Despite volatile market conditions, Sanofi has decided to move forward with the listing process of EUROAPI.

As an independent stand-alone company, EUROAPI will be able to fully unlock its growth potential, offering the best alignment of strategy, value creation and financial objectives for all of Sanofi’s shareholders.

With a diversified technology portfolio, EUROAPI is positioned as the world’s leading manufacturer of small molecule API (including complex chemical synthesis molecules, biochemical molecules from fermentation and highly potent molecules).

It was the world’s second largest manufacturer of APIs (including both small and large molecules such as peptides and oligonucleotides) in 2021 and number seven in the global CDMO (Contract Development and Manufacturing Organization) market in 2020.

EUROAPI develops, manufactures, markets and distributes APIs and intermediates used in the formulation of medicines for human and veterinary use, both from originators and generics, through its API Solutions business and CDMO activities.

Drawing on more than 150 years of experience in the growing API market, EUROAPI has a network of six production sites, all of which are located in Europe, and delivers around 200 APIs to approximately 530 customers in over 80 countries.

The company will be able to rely on the expertise of around 3,350 employees and expects to achieve consolidated sales of around EUR 1 billion in the year ending December 31, 2022.”

https://www.sanofi.com/en/media-room/press-releases/2022/2022-03-18-12-48-38-2405963

FDA, Reagan-Udall Foundation to Hold Important Public Workshop to Discuss Naloxone Access

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March 17, 2022: “The FDA will host a virtual public workshop on Mar. 29, to discuss critical questions around access to naloxone, a drug used to reverse opioid overdoses.

The workshop is a collaboration with the Reagan-Udall Foundation for the FDA.

“An integral part of our efforts to combat opioid-related drug overdose is making naloxone more readily available and accessible,” said Patrizia Cavazzoni, M.D., director of the FDA’s Center for Drug Evaluation and Research.

“We will continue to work with other federal, state and local officials as well as health care providers, patients and community-based organizations across the country to explore innovative and meaningful approaches that place naloxone in the hands of those who need it most.”

The workshop will provide an in-depth discussion to review the current landscape of naloxone availability, address perceived barriers to naloxone access, including current misperceptions, and address questions posed by various groups on this subject.

In addition to exploring these diverse topics, various stakeholders, including harm-reduction specialists, physicians, pharmacists and regulators will also share their experiences in addressing the availability of naloxone for opioid overdose. 

Naloxone remains a critical tool for individuals, families, first responders and communities to help reduce opioid overdose deaths.

The FDA has taken a number of steps over the last several years to support increased availability and awareness of naloxone products, including encouraging manufacturers to pursue approval of over-the-counter naloxone products, requiring drug manufacturers for all opioid pain relievers and medicines to treat opioid use disorder to add new recommendations about naloxone to the prescribing information, and extending the expiration date of naloxone nasal spray from 24 months to 36 months. 

The workshop further underscores the agency’s ongoing commitment to gain valuable insight from various stakeholders to increase access and availability to this potentially lifesaving treatment.”

https://www.fda.gov/news-events/press-announcements/fda-reagan-udall-foundation-hold-important-public-workshop-discuss-naloxone-access

Sanofi & Seagen collaborates for multiple novel antibody-drug conjugates

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March 16, 2022. Sanofi and Seagen Inc. announced an exclusive collaboration agreement to design, develop, and commercialize antibody-drug conjugates (ADCs) for up to three cancer targets.

The collaboration will utilize Sanofi’s proprietary monoclonal antibody (mAb) technology and Seagen’s proprietary ADC technology.

ADCs are antibodies engineered to deliver potent anti-cancer drugs to tumor cells expressing a specific protein and Sanofi currently has one ADC in development.

John Reed, M.D., Ph.D.
Global Head of Research and Development, Sanofi
“This collaboration will enable the synergistic combination of molecules and platforms to produce candidate medicines with the potential of bringing renewed hope to cancer patients and their families. 

We look forward to joining forces with Seagen to collaboratively design and develop promising medicines by advancing antibody-drug conjugate science.”

Clay Siegall, Ph.D.
President and Chief Executive Officer, Seagen
“We are excited to be working with Sanofi, a global biopharmaceutical leader, to identify new ways to potentially address unmet medical needs of cancer patients. 

Jointly developing novel ADCs by combining antibodies from Sanofi with Seagen’s proprietary ADC technology, aligns with our strategic priorities to expand the global potential of our pipeline with new first- or best-in-class programs.”

Under the terms of the collaboration, Seagen and Sanofi will co-fund global development activities and share equally in any future profits.

In addition, Sanofi will make an undisclosed payment to Seagen for each of the three targets as they are selected. The first target under the collaboration has already been designated.”

https://www.sanofi.com/en/media-room/press-releases/2022/2022-03-16-11-18-19-2404147

AZ reaches settlement agreement resolving patent litigation related to Ultomiris

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March 17, 2022: “Alexion, AstraZeneca’s Rare Disease group, has entered into a settlement agreement with Chugai Pharmaceutical Co., Ltd. (Chugai), resolving all patent disputes between the two companies related to Ultomiris (ravulizumab).

In accordance with the settlement agreement, Alexion and Chugai have taken steps to withdraw patent infringement proceedings filed with US District Court for the District of Delaware and Tokyo District Court. 

Marc Dunoyer, Chief Executive Officer, Alexion, said: “With this settlement, we will continue to advance our Ultomiris development programmes in new indications and focus on our mission to transform the lives of people affected by rare diseases.”

Financial considerations
Under the terms of the agreement, Alexion will make a single payment of $775m in the second quarter of 2022, for which a charge will be recognised through the non-core P&L in the first quarter of 2022.

No further amounts are payable by either party. The settlement does not impact AstraZeneca’s financial guidance for 2022.

Notes

Ultomiris patent proceedings
US
In November 2018, Chugai filed a lawsuit against Alexion in the Delaware District Court alleging that Ultomiris infringes US patent No. 9,890,377 held by Chugai.

Upon issuance of US patent No. 10,472,623 in November 2019, Chugai filed a second lawsuit in the same court alleging that Ultomiris also infringes that patent.

The two lawsuits were consolidated in December 2019.

Japan
In December 2018, Chugai filed a lawsuit in the Tokyo District Court against Alexion Pharma GK alleging that Ultomiris infringed two Japanese patents (Japanese Patent No. 4954326 and No. 641743) held by Chugai. Chugai’s complaint sought unspecified damages and certain injunctive relief.

Also beginning in 2016, Alexion had challenged the validity of four of Chugai’s Japanese patents.

The IP High Court in Japan had found these patents invalid. Chugai filed a correction of these patents with the Japanese Patent Office.

The Japanese Patent Office found the corrected patents invalid, and Chugai appealed the Patent Office’s decision to the IP High Court in Japan.  

Europe
Beginning in 2016, Alexion challenged the validity of five of Chugai’s European patents.

One patent was maintained by the Opposition Division of the European Patent Office while four were revoked.

Three of the five decisions by the Opposition Division have been appealed to the Boards of Appeal for the European Patent Office.

Ultomiris
Ultomiris (ravulizumab), the first and only long-acting C5 complement inhibitor, offers immediate, complete, and sustained complement inhibition.

The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system.

When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. 

Ultomiris is administered intravenously every eight weeks or, for paediatric patients less than 20kg, every four weeks, following a loading dose. 

Ultomiris is approved in the US for the treatment of adults and children (one month of age and older) with PNH; in the EU for adults, as well as for children (with a body weight of 10kg or above) and adolescents with PNH who experience haemolysis with clinical symptom(s) indicative of high disease activity, as well as for individuals who are clinically stable after having been treated with Soliris for at least the past six months; and in Japan as a treatment for adults with PNH.

It is also approved in the US for aHUS to inhibit complement-mediated thrombotic microangiopathy in adult and paediatric (one month of age and older) patients, in the EU for the treatment of adults and children with a body weight of at least 10kg with aHUS, as well as in Japan for adults and children with aHUS.”

https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2022/astrazeneca-reaches-settlement-agreement-resolving-patent-litigation-related-to-ultomiris.html

AZ launches global R&D Postdoctoral Challenge to accelerate scientific discovery and diversity

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March 17, 2022: “AstraZeneca launched a global R&D Postdoctoral Challenge to help accelerate ideas to transform the treatment of some of the world’s most complex diseases.

The challenge, launched at EXPO 2020 Dubai, invites final year MD and/or PhD students and postdoctoral researchers from across the world to propose their innovative ideas to help accelerate drug discovery and development across AstraZeneca’s core disease areas.

Successful candidates will be awarded a fully funded postdoctoral research position and join the vibrant scientific community within AstraZeneca.

Working alongside a leading university, the researchers will also receive access to in-house expertise, compounds, novel tools and technologies and mentoring support to develop their ideas and innovate.

Prof. Sir Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “The events of the past two years clearly show the need to push the boundaries of medical science has never been more urgent.

Rapid progress in disease understanding, as well as scientific and technological advances are genuinely changing our expectations of what is possible.

We are delighted to launch the R&D Postdoctoral Challenge to support the next generation of science leaders and help them translate their ideas into meaningful benefits for patients.”

Shortlisted applicants will have the chance to pitch their research ideas to a panel consisting of AstraZeneca and external life science leaders in October, with the selection of finalists decided later in the year.

Proposals will be reviewed based on scientific merit, and potential to create real impact for patients, society and healthcare systems.

Further information on the R&D Postdoctoral Challenge, including entry criteria and details on how to submit innovative research proposals, can be found at: https://openinnovation.astrazeneca.com/rd-postdoctoral-challenge.html.

The R&D Postdoctoral Challenge forms part of AstraZeneca’s Early Talent programmes, nurturing the science leaders of tomorrow and encouraging diversity of thought within an environment that enables science to thrive.

AstraZeneca’s global R&D footprint and productivity
In 2021 AstraZeneca invested $8 billion in R&D, around 21% of the Company’s turnover, in order to continue to discover and develop medicines which transform the lives of patients.

The Company has three world class strategic R&D centres including The Discovery Centre (DISC) in Cambridge in the UK, one in Gaithersburg, Maryland in the greater Washington, D.C. region of the US, and another in Gothenburg in Sweden, as well as further hubs across the world.

It has integrated R&D teams and accelerated decision-making processes, using its unique scientific capabilities, to deliver one of the most productive pipelines in the industry.

Since 2005, AstraZeneca has achieved an almost six-fold improvement in the proportion of its pipeline molecules that have advanced from preclinical investigation to completion of Phase III clinical trials – from 4% to 23%.

This improvement moves AstraZeneca well above the current industry average success rate of 14% in the 2018-2020 timeframe.1

Of the Company’s 80,000 employees, more than 13,000 work exclusively in R&D. In 2021, its scientists published a total of 871 manuscripts, with 196 in high impact peer-review journals (impact factor greater than or equal to 15 according to Reuters five-year rating), compared to one in 2010.”

https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2022/astrazeneca-launches-global-rd-postdoctoral-challenge-to-accelerate-scientific-discovery-and-diversity.html

FDA Approves First Generic of Symbicort to Treat Asthma and COPD

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March 15, 2022: “The U.S. FDA approved the first generic of Symbicort (budesonide and formoterol fumarate dihydrate) Inhalation Aerosol for the treatment of two common pulmonary health conditions: asthma in patients six years of age and older; and the maintenance treatment of airflow obstruction and reducing exacerbations for patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

This complex generic drug-device combination product, which is a metered-dose inhaler, should not be used to treat acute asthma attacks.

“Today’s approval of the first generic for one of the most commonly prescribed complex drug-device combination products to treat asthma and COPD is another step forward in our commitment to bring generic copies of complex drugs to the market, which can improve quality of life and help reduce the cost of treatment,” said Sally Choe, Ph.D., director of the Office of Generic Drugs in the FDA Center for Drug Evaluation and Research.

“This reflects the FDA’s continued efforts to increase competition and access to quality, safe, effective and affordable medicines for patients and consumers.” 

Asthma impacts 25 million people, more than five million of whom are children, while COPD afflicts more than 16 million, according to the National Heart, Lung, and Blood Institute.

Asthma is a chronic, long-term condition that affects the airways in the lungs, which can be worsened by physical activity and most often starts during childhood.

It can cause wheezing (a whistling sound when breathing), shortness of breath, and coughing. COPD, which includes emphysema and chronic bronchitis, is a long-term, chronic disease that causes airflow blockage and makes it difficult to breathe. 

This drug-device combination product is a metered-dose inhaler (MDI), which contains both budesonide (a corticosteroid that reduces inflammation) and formoterol (a long-acting bronchodilator that relaxes muscles in the airways to improve breathing).

Two inhalations, two times a day (usually morning and night, about 12 hours apart), treat both diseases by preventing symptoms, such as wheezing for those with asthma, and by helping with better breathing, for those with COPD.

The inhaler is approved for two strengths (160/4.5 mcg/actuation and 80/4.5 mcg/actuation).

The most common side effects associated with budesonide and formoterol fumarate dihydrate oral inhalation aerosol for those with asthma are nasopharyngitis (swelling of nasal passages and back of throat), headache, upper respiratory tract infection, pharyngolaryngeal (nose and mouth) pain, sinusitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and oral candidiasis (thrush).

For those with COPD, the most common side effects are nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection.

The FDA regularly takes steps to help guide industry through the development process for generic drug products, including combination products, such as MDIs, that consist of a drug and a device.

To further facilitate generic drug development, and to assist the generic pharmaceutical industry in this process, the FDA publishes product-specific guidances (PSGs) describing the agency’s current thinking and expectations on how to develop generic drug products that are therapeutically equivalent to their brand name counterparts.

In June 2015, FDA published a PSG for budesonide and formoterol fumarate dihydrate inhalation aerosol.

The FDA requires sponsors to submit appropriate data and information to demonstrate that complex generic drug-device combination products meet the agency’s rigorous approval standards.

These standards ensure that generic drug products are as safe and effective as their brand name equivalents and meet the same high quality standards.

Complex products are medical products where uncertainty concerning the approval pathway or possible alternative approaches to product development can benefit from early scientific engagement, such as products with complex active ingredients and drug-device combination products.

Since drug-device combination products can be more challenging to develop, fewer exist, resulting in less market competition.

Addressing the challenges related to complex generics, and promoting more generic competition to these medicines, is a key part of the FDA’s Drug Competition Action Plan, and the agency’s efforts to promote patient access and more affordable medicines.

The FDA granted approval of this generic budesonide and formoterol fumarate dihydrate inhalation aerosol to Mylan Pharmaceuticals, Inc.”

https://www.fda.gov/news-events/press-announcements/fda-approves-first-generic-symbicort-treat-asthma-and-copd

Abivax reports promising results in rheumatoid arthritis

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March 10, 2022: “Abivax SA, a clinical-stage biotechnology company developing novel therapies that modulate the immune system to treat chronic inflammatory diseases, viral infections, and cancer, reports promising results from its phase 2a maintenance trial in rheumatoid arthritis (RA) after one year of continued daily treatment with 50mg ABX464.

Prof. Paul Emery, M.D., FMedSci, Versus Arthritis Professor of Rheumatology, Director of the Leeds Musculoskeletal Biomedical Research Centre, Leeds Teaching Hospitals Trust, Leeds Institute of Rheumatic and Musculoskeletal Medicine, UK, commented: 

“The high levels of maintained response rates within this phase 2a maintenance trial with ABX464 in rheumatoid arthritis patients, especially when it comes to ACR50 and ACR70 responses, look very promising.

The molecule also demonstrated a good safety profile, and no serious infections were observed.

Along with its very different mode of action and clinical profile, ABX464 has the potential to play an important role in the future management of rheumatoid arthritis patients.”

Prof. William Robinson, M.D., Ph.D., Chief of Division of Immunology and Rheumatology, Stanford University, US, added: “Patients suffering from chronic inflammatory diseases, such as RA, often struggle to find a suitable treatment that remains efficacious over time.

These maintenance data are very encouraging and demonstrate a potential long-term efficacy and tolerability of ABX464 for the treatment of RA, even in patients who previously did not respond or stopped responding to available therapies.”

Prof. Hartmut J. Ehrlich, M.D., CEO of Abivax, said: “These results clearly support the continued clinical development of ABX464 for the treatment of RA.

Furthermore, they are consistent with the data generated in our phase 2a and 2b ulcerative colitis trials and suggest that ABX464 has the capacity to address a broad range of chronic inflammatory indications, a disease field with a persistent high medical need and with millions of patients waiting for new, safe drugs with durable efficacy.”

After the 12-week randomized, placebo-controlled ABX464 phase 2a induction study in 60 RA patients, 67% of the patients (40/60) enrolled in the open-label extension maintenance study to receive 50mg ABX464 orally once a day for an additional 52 weeks.

58% of the patients (23/40) suffering from moderate to severe active RA completed 52 weeks of chronic treatment with ABX464.

Efficacy of 50mg once daily ABX464 was assessed by the DAS28-CRP remission (DAS28-CRP < 2.62) and the ACR20/50/70 rates:

At week 52*Full analysis set
(n=40)
(non-responder imputation)
Observed cases
(n=23)
Remission
As per DAS28-CRP < 2.6
13 (33%)13 (57%)
Low Disease Activity
As per DAS28-CRP < 3.2
17 (43%)17 (74%)
ACR2023 (58%)23 (100%)
ACR5019 (48%)19 (83%)
ACR7012 (30%)12 (52%)

            * Results based on a soft lock database review

57% of the patients (13/23) were in remission at week 52, assessed by the DAS28-CRP (< 2.6), corresponding to 33% (13/40) using the full analysis set (FAS).

All 23 patients (100%) who completed 52 weeks of treatment achieved at least an ACR20 response, which translates into 58% (23/40) in the FAS.

It is remarkable, that according to the observed cases population, 83% (19/23) and 52% (12/23) achieved even an ACR50 and ACR70 response respectively, corresponding to 48% (19/40) and 30% (12/40) according to the FAS.

17 patients discontinued the study during the first year of maintenance treatment due to either mild to moderate adverse events or worsening RA.

ABX464 was safe and the nature of the adverse events is consistent with what has been observed in more than 1,000 subjects who have so far been treated in other clinical trials with ABX464 across different indications.

At present, some UC patients have been continuously treated for four years.

ABX464 phase 2a induction and maintenance studies in rheumatoid arthritis

The placebo-controlled clinical phase 2a study was designed to evaluate the safety, tolerability and preliminary efficacy of two oral dose-levels of ABX464 administered once daily (50mg or 100mg), in combination with methotrexate (MTX).

60 patients who had an inadequate response to MTX and/or to one or more anti-tumor necrosis factor alpha (TNFα) biological therapeutics participated in this randomized and double-blind trial.

The study was conducted in 21 study centers across four European countries (France, Belgium, Poland and Hungary).

After the end of the 12-week induction study, 40 patients continued their treatment in the maintenance study with a once-daily oral dosing of 50mg ABX464.

In June 2021, Abivax communicated the results of the induction phase of its phase 2a clinical study of ABX464 administered in combination with methotrexate (MTX) for the treatment of active moderate to severe RA.

The primary endpoint of this study, safety and tolerability, was met with 50mg ABX464 once daily, demonstrating a good safety and tolerability profile in the overall patient population during the 12-week induction phase.

Epidemiology and market size in rheumatoid arthritis
In 2021, there were an estimated 3.8M diagnosed cases of rheumatoid arthritis in G7 countries (US, France, Germany, Italy, Spain, UK and Japan).

The total market size in RA is currently USD 22.3B annually, based on 2021 pharmaceutical sales estimates for rheumatoid arthritis in these countries.”

https://www.abivax.com/press-releases/

Sanofi provides update on Phase 2 study evaluating amcenestrant in breast cancer

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March 14, 2022: “The Phase 2 AMEERA-3 clinical trial evaluating amcenestrant, an investigational optimized oral selective estrogen receptor degrader (SERD), did not meet its primary endpoint of improving progression-free survival (PFS) as assessed by an independent central review.

The trial evaluated amcenestrant as monotherapy compared to endocrine treatment of physician’s choice in patients with locally advanced or metastatic estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer who progressed on or after hormonal therapies.

No new safety signals were identified and the safety profile of amcenestrant in AMEERA-3 was consistent with earlier studies.

John Reed, MD, PhD
Head of Research and Development at Sanofi
“This Phase 2 trial evaluated amcenestrant as a monotherapy in a patient population with advanced disease where limited treatment options remain. 

While we are disappointed with the AMEERA-3 results, we continue to investigate amcenestrant in patients with earlier stages of breast cancer with different tumor profiles and where different standard of care treatments are used.”

Sanofi will continue to assess data from the AMEERA-3 trial and work with investigators on the publication of the full results. The ongoing clinical trial program for amcenestrant continues as planned, including AMEERA-5 and AMEERA-6.

Amcenestrant is an optimized oral SERD that binds to the estrogen receptors (ER) in breast cancer cells to inhibit their normal function and trigger degradation so they can no longer be used by tumor cells to grow.

Amcenestrant is currently under clinical investigation and its safety and efficacy have not been evaluated by any regulatory authority.

About the AMEERA-3 trial

AMEERA-3 was an open-label, Phase 2 randomized trial evaluating the efficacy and safety of amcenestrant as a monotherapy compared to single-agent endocrine treatment of the physician’s choice in patients with ER+, HER2- locally advanced or metastatic breast cancer with prior exposure to hormonal therapies.

The primary objective of AMEERA-3 was to determine whether amcenestrant improved PFS assessed by an independent central review compared to endocrine monotherapy.

The key secondary efficacy endpoint was overall survival and other secondary endpoints were objective response rate, disease control rate, clinical benefit rate and duration of response.

The study also compared the overall safety profile in the two treatment arms and evaluated health-related quality of life in the two treatment arms based on patient-reported outcomes.

About the amcenestrant clinical program

The comprehensive development program for amcenestrant has been designed to evaluate its potential as an oral endocrine backbone therapy across treatment lines, including: as a single agent in second-line or later lines of treatment of ER+/HER2- metastatic breast cancer (MBC) (AMEERA-3), in combination with palbociclib in the first-line treatment of ER+/HER2- MBC (AMEERA-5), and to explore its potential in early-stage breast cancer patients in the adjuvant setting (AMEERA-6).

Initiated in late 2020, the Phase 3 AMEERA-5 clinical trial is now fully enrolled.

The Phase 3 AMEERA-6 trial, in partnership with the Breast International Group (BIG), the European Organization for Research and Treatment of Cancer (EORTC), and the Alliance Foundation Trials (AFT) is now enrolling.”

Update on US regulatory review of Fasenra in chronic rhinosinusitis with nasal polyps

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 March 14, 2022: “The US FDA has issued a complete response letter (CRL) regarding the sBLA for Fasenra (benralizumab) for patients with inadequately controlled chronic rhinosinusitis with nasal polyps (CRSwNP).

The sBLA submitted to the FDA by AstraZeneca included data from the OSTRO Phase III trial, which met both co-primary endpoints with a safety profile consistent with the known profile of the medicine.

The CRL requested additional clinical data and the Company is working closely with the FDA regarding next steps.

The Company remains committed to bringing Fasenra to patients with CRSwNP and a second Phase III trial, ORCHID, in this indication is ongoing.

Fasenra is currently approved as an add-on maintenance treatment for severe eosinophilic asthma in the US, EU, Japan and other countries and is approved for self-administration in the US, EU and other countries.

The FDA granted Orphan Drug Designation (ODD) for Fasenra for eosinophilic granulomatosis with polyangiitis in 2018, and hypereosinophilic syndrome and eosinophilic esophagitis (EoE) in 2019.

In November 2021, the FDA also granted ODD for Fasenra for eosinophilic gastroenteritis (EGE) and eosinophilic gastritis (EG), and a Fast Track Designation for the treatment of EG with or without EGE in the US.”

FDA Orders Philips Respironics to Notify Patients Regarding Recall of Certain Breathing Assistance Machines

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March 10, 2022: “The U.S. FDA issued a notification order to Philips Respironics requiring the company to notify patients and others of the company’s June 14, 2021, recall of certain Philips Respironics ventilators, continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP) machines, and the unreasonable risk of substantial harm to the public health posed by the degradation of the polyester-based polyurethane (PE-PUR) sound abatement foam used in those products.

The FDA has determined that this order is necessary to eliminate the unreasonable risk of harm posed by the recalled products, because the company’s notification efforts to date have been inadequate

The FDA has heard the frustration expressed by patients and durable medical equipment suppliers who are unaware of the recall and have received insufficient information on their next steps regarding the recall process,” said Jeff Shuren, M.D., J.D., director of the FDA’s Center for Devices and Radiological Health.

“Taking this action today enables the FDA to mandate that Philips Respironics improve its communication about the recall and the serious risk posed by the foam used in the recalled products with patients and the public and to ensure that individuals who rely on these essential devices are receiving the important information they need from the company.”  

The FDA is ordering Philips Respironics to notify all device users, durable medical equipment (DME) suppliers, distributors, retailers, and health care providers who prescribe the products about the recall and the health risks posed by the foam used in the recalled products.

The order also directs Philips to maintain language to patients regarding the risk of using ozone cleaners on the recalled devices on their main webpage for the recall, and to provide instructions for device users to register their devices on the Philips website. 

Along with these actions, the FDA recommends additional measures Philips can take to better communicate with the public regarding the recall.

Specifically, the FDA recommends that Philips provide monthly updates to device users who register their devices on the Philips website that include information on expected time for replacement and current rate of replacement of recalled devices.

The FDA also recommends that Philips provide detailed information to device users, DME suppliers, distributors, retailers, and healthcare providers on the replacement process. 

In June 2021, Philips Respironics initiated a recall of certain ventilators, CPAP and BiPAP machines due to potential health risks related to PE-PUR sound abatement foam used in those devices.

This particular foam may break down and can result in serious injury, which can be life-threatening, cause permanent impairment and/or require medical intervention to prevent permanent injury to users. 

Since the initiation of the recall, the FDA has engaged with Philips on several fronts about the effectiveness of its communications with the public regarding the recall and the risks presented by the recalled products and has expressed concern that it is likely a significant portion of patients and consumers using the recalled products are unaware of the health risks presented by those products. “

The FDA is issuing this order under section 518(a) of the Federal Food, Drug, and Cosmetic Act. Under this authority, the FDA may order a manufacturer to provide notification if the FDA determines that a device presents an “unreasonable risk of substantial harm to the public health” and such notification is necessary to “eliminate the unreasonable risk of such harm and no more practical means are available [under the Federal Food, Drug, and Cosmetic Act] to eliminate such risk.”

The FDA may order that adequate notification be provided to device users, health care providers who prescribe or use the device, and any other person who should receive notification to eliminate such risk. 

The order directs Philips to provide the notification described in the order within 45 days of its issuance.”

https://www.fda.gov/news-events/press-announcements/fda-orders-philips-respironics-notify-patients-regarding-recall-certain-breathing-assistance

Pfizer Initiates Phase 2/3 Study of Novel COVID-19 Oral Treatment in Pediatric Participants

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March 09, 2022: “Pfizer Inc. announced that it has initiated a Phase 2/3 study, EPIC-PEDS (Evaluation of Protease Inhibition for COVID-19 in Pediatric Patients), to evaluate the safety, pharmacokinetics, and efficacy of Pfizer’s PAXLOVID™ (nirmatrelvir [PF-07321332] tablets and ritonavir tablets) in non-hospitalized, symptomatic, pediatric participants with a confirmed diagnosis of COVID-19 who are at risk of progression to severe disease.

“Since the beginning of the pandemic, more than 11 million children under the age of 18 in the United States alone have tested positive for COVID-19, representing nearly 18% of reported cases and leading to more than 100,000 hospital admissions.

There is a significant unmet need for outpatient treatments that can be taken by children and adolescents to help prevent progression to severe illness, including hospitalization or death,” said Mikael Dolsten, Chief Scientific Officer and President, Worldwide Research, Development and Medical, Pfizer.

“PAXLOVID is already authorized or approved in many countries around the world, with more than 1.5 million treatment courses delivered thus far and 30 million expected by July to help combat this devastating disease.

We are proud to expand studies of our novel COVID-19 treatment to include pediatric participants to further evaluate the safety and efficacy of this treatment in this important population.”

The Phase 2/3 trial is an open-label, multi-center, single-arm study in approximately 140 pediatric participants under 18 years of age.

Initial enrollment features two cohorts; Cohort 1 includes participants aged 6 to 17 weighing at least 40 kg [88 lbs], and Cohort 2 includes those aged 6 to 17 weighing more than 20 kg [44 lbs] and less than 40 kg [88 lbs].

  • Participants enrolled in Cohort 1 will receive PAXLOVID (nirmatrelvir/ritonavir 300 mg/100 mg) orally twice daily for five days (10 doses total), the current authorized dosing for pediatric patients 12 years of age and older weighing at least 40kg.
  • Participants enrolled in Cohort 2 will receive PAXLOVID (nirmatrelvir/ritonavir 150 mg/100 mg) orally twice daily for five days (10 doses total).

Pfizer is also working to develop an age-appropriate formulation for three additional planned cohorts of younger than 6 years old and will enroll the trial to include these younger age groups as data from Cohorts 1 and 2 and the new formulation are available.

An independent Data Monitoring Committee (DMC) will review safety data of participants in each cohort.

Data from the Phase 2/3 study of non-hospitalized, high-risk adults with COVID-19 showed PAXLOVID reduced risk of hospitalization or death by 89% (within three days of symptom onset) and 88% (within five days of symptom onset) from any cause compared to placebo, with no deaths observed in the treatment group.

Treatment-emergent adverse events were comparable between PAXLOVID (23%) and placebo (24%), most of which were mild in intensity.

The safety and effectiveness of PAXLOVID have not yet been directly established in pediatric patients.

Although other PAXLOVID clinical trials did not include participants under the age of 18, the FDA authorized PAXLOVID for emergency use in pediatric patients 12 years of age and older weighing at least 40 kg [88lbs] as pharmacokinetic-pharmacodynamic (PK/PD) modeling determined that the authorized adult dosing regimen would result in comparable blood concentration levels of PAXLOVID in this population and the adults with similar body weight who were included in the EPIC-HR trial.

Data from the EPIC-PEDS study will provide further support for the dose recommendations in this population, as well as potentially expand the indication to younger age groups and lower weights.

PAXLOVID is currently authorized or approved in more than 50 countries across the globe.

Please see Full Emergency Use Authorization (EUA) Prescribing Information available at www.fda.gov and www.COVID19oralRx.com.

Our Commitment to Equitable Access

Pfizer is committed to working toward equitable access to PAXLOVID for all people, aiming to deliver safe and effective antiviral therapeutics as soon as possible and at an affordable price.

During the pandemic, Pfizer will offer its oral therapy through a tiered pricing approach, pending country authorization or approval, based on the income level of each country to promote equity of access across the globe.

High and upper-middle income countries will pay more than lower income countries.

Pfizer continues to invest to support the manufacturing and distribution of PAXLOVID, including exploring potential contract manufacturing options.

As a result of these efforts, Pfizer has raised its production projections, with the ability to produce up to 120 million courses of treatment by the end of 2022, pending global demand.

The company has initiated bilateral outreach to more than 100 countries around the world and has entered into agreements with multiple countries.

Additionally, Pfizer has signed a voluntary license agreement with the Medicines Patent Pool (MPP) for its oral treatment to help expand access, pending country regulatory authorization or approval, in 95 low- and middle-income countries that account for approximately 53% of the world’s population.

About PAXLOVID™ (nirmatrelvir [PF-07321332] tablets and ritonavir tablets)

PAXLOVID is a SARS-CoV-2 main protease (Mpro) inhibitor (also known as SARS-CoV-2 3CL protease inhibitor) therapy.

It was developed to be administered orally so that it can be prescribed at the first sign of infection or, pending clinical success of the rest of the EPIC development program and subject to regulatory authorization, at first awareness of an exposure – potentially helping patients avoid severe illness (which can lead to hospitalization and death) or avoid disease development following contact with a household member who contracts COVID-19.

Nirmatrelvir [PF-07321332], which originated in Pfizer laboratories, is designed to block the activity of the Mpro, an enzyme that the coronavirus needs to replicate.

Co-administration with a low dose of ritonavir helps slow the metabolism, or breakdown, of nirmatrelvir in order for it to remain active in the body for longer periods of time at higher concentrations to help combat the virus.

Nirmatrelvir is designed to inhibit viral replication at a stage known as proteolysis, which occurs before viral RNA replication.

In preclinical studies, nirmatrelvir did not demonstrate evidence of mutagenic DNA interactions.

Current variants of concern can be resistant to treatments that work by binding to the spike protein found on the surface of the SARS-CoV-2 virus.

PAXLOVID, however, works intracellularly by binding to the highly conserved Mpro of the SARS-CoV-2 virus to inhibit viral replication.

Nirmatrelvir has shown consistent in vitro antiviral activity against earlier and current variants of concern (i.e., Alpha, Beta, Delta, Gamma, Lambda, Mu, and Omicron).

PAXLOVID is generally administered at a dose of 300 mg (two 150 mg tablets) of nirmatrelvir with one 100 mg tablet of ritonavir, given twice-daily for five days.

One carton contains five blister packs of PAXLOVID, as co-packaged nirmatrelvir tablets with ritonavir tablets, providing all required doses for a full five-day treatment course.

About the EPIC Development Program

The EPIC (Evaluation of Protease Inhibition for COVID-19) Phase 2/3 development program for PAXLOVID consists of four clinical trials spanning a broad spectrum of participants, including adults who have been exposed to the virus through household contacts, adults at both standard risk and high risk of progressing to severe illness, and children under the age of 18 at risk of progressing to severe disease.​

In July 2021, Pfizer initiated the first of these trials, known as EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients), a randomized, double-blind study of non-hospitalized adults with COVID-19, who are at high risk of progressing to severe illness.

At the recommendation of an independent Data Monitoring Committee and in consultation with the U.S. FDA, Pfizer ceased further enrollment into the study in early November 2021 due to the overwhelming efficacy demonstrated in these results.

Findings from the EPIC-HR final analysis were published online in The New England Journal of Medicineon February 16, 2022.

In August 2021, Pfizer began the Phase 2/3 EPIC-SR (Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients) study to evaluate efficacy and safety in adults with a confirmed diagnosis of SARS-CoV-2 infection who are at standard risk (i.e., low risk of hospitalization or death).

Interim data from this study have been reported. Pfizer is currently expanding the population of the ongoing EPIC-SR study by approximately 800 participants and expects to share results later this year.

In September 2021, Pfizer initiated the Phase 2/3 EPIC-PEP (Evaluation of Protease Inhibition for COVID-19 in Post-Exposure Prophylaxis) study to evaluate efficacy and safety in adults exposed to SARS-CoV-2 by a household member. This trial is also ongoing, and Pfizer expects to share results later this year.”

https://www.pfizer.com/news/press-release/press-release-detail/pfizer-initiates-phase-23-study-novel-covid-19-oral