Stem Cell Clinic

Janssen Announces Health Canada Approval of DARZALEX* SC, a New Subcutaneous Formulation for the Treatment of Patients with Multiple Myeloma – Canada…

DARZALEX SC reduces administration time from hours to minutes and demonstrates consistent efficacy with a reduction in administration-related reactions compared to intravenous DARZALEX (daratumumab)

TORONTO, Aug. 4, 2020 /CNW/ - The Janssen Pharmaceutical Companies of Johnson & Johnson announced today that Health Canada has approved DARZALEX SC (daratumumab), a new subcutaneous formulation of daratumumab.1 DARZALEX SC is approved in four regimens across five indications in patients with multiple myeloma, most notably newly diagnosed, transplant-ineligible patients as well as relapsed or refractory patients. As a fixed-dose formulation, DARZALEX SC can be administered over approximately three to five minutes, significantly less time than intravenous (IV) DARZALEX, which is administered over hours.2 DARZALEX SC is the only subcutaneous CD38-directed antibody approved in the treatment of multiple myeloma.

In the Phase 3 COLUMBA study published in The Lancet, DARZALEX SC demonstrated a consistent overall response rate (ORR) and pharmacokinetics and a similar safety profile compared with IV DARZALEXin patients with relapsed or refractory multiple myeloma. In addition, there was a nearly two-thirds reduction in systemic administration-related reactions (ARRs) for DARZALEX SC compared to IV DARZALEX(13 per cent vs. 34 per cent, respectively).3

"DARZALEX has become a backbone therapy in the treatment of multiple myeloma, supported by a robust body of evidence in both the frontline and relapsed and refractory settings," says Dr. Darrell White, Hematologist, Queen Elizabeth II Health Sciences Centre, Halifax. "With this new subcutaneous formulation, not only is treatment much more convenient for patients, but it will also play a very important role in reducing wait times and the burden on our busy healthcare system, especially during this time."

The approval is based on data from the Phase 3 COLUMBA and Phase 2 PLEIADES studies.4,5In the COLUMBA study, the ORR was non-inferior for patients taking DARZALEX SC as monotherapy compared to those taking IV DARZALEXas monotherapy (41 per cent vs. 37 per cent, respectively).6 Additionally, in the Phase 2 PLEIADES study evaluating the efficacy and safety of DARZALEXSC in combination therapies, objective responses were demonstrated in combination with bortezomib, melphalan and prednisone (D-VMP) in newly diagnosed transplant ineligible patients. In addition, objective responses were demonstrated in combination with lenalidomide and dexamethasone (D-Rd) in relapsed or refractory patients who received one prior line of therapy.7In a pooled safety population of 490 patients who received DARZALEXSC as monotherapy or in combination, the ARR rate was 11 per cent.8

DARZALEX SC is approved in all current IV indicationsincluding (1) in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant, (2) in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy, (3) in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy, and (4) as monotherapy, in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.9

Active discussions are ongoing with public insurers to determine how DARZALEX SC can be made accessible for both relapsed or refractory patients as well as newly diagnosed, transplant ineligible patients.

"This approval exemplifies Janssen's mission and commitment to bringing together passion, science and ingenuity to advance novel solutions for patients," said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, LLC.

About the COLUMBA Study The randomised, open-label, multicenter Phase 3 COLUMBA study included 522 patients (median age of 67 years) with multiple myeloma who had received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or whose disease was refractory to both a PI and an ImiD. In the arm that received DARZALEX SC (n=263), patients received a fixed dose of DARZALEX SC 1,800 milligrams (mg), co-formulated with recombinant human hyaluronidase PH20 (rHuPH20) 2,000 Units per milliliter (U/mL), subcutaneously weekly for Cycles 1 2, every two weeks for Cycles 3 6 and every four weeks for Cycle 7 and thereafter. In the IV DARZALEXarm (n=259), patients received DARZALEXfor IV infusion 16 milligrams per kilogram (mg/kg) weekly for Cycles 1 2, every two weeks for Cycles 3 6 and every four weeks for Cycle 7 and thereafter. Each cycle was 28 days. In the arm that received DARZALEX SC, it was given in a fixed volume of 15 mL over three to five minutes; the median injection time was five minutes. In the arm that received the IV administration, the median durations of the first, second and subsequent IV DARZALEXinfusions were 7.0, 4.3 and 3.4 hours, respectively. Patients in both arms continued treatment until disease progression or unacceptable toxicity.10,11

About the PLEIADES Study The non-randomised, open-label, parallel assignment Phase 2 PLEIADES study included adults with multiple myeloma, including 67 patients with newly diagnosed multiple myeloma who were treated with 1,800 mg of DARZALEX SC in combination with bortezomib, melphalan, and prednisone (D-VMP) and 65 patients with relapsed or refractory disease who were treated with 1,800 mg of DARZALEX SC plus lenalidomide and dexamethasone (D-Rd). The primary endpoint for the D-VMP and D- Rd cohorts was overall response rate.12

About DARZALEXand DARZALEX SCDARZALEX is the first CD38-directed monoclonal antibody (mAb) approved to treat multiple myeloma and in 2020, DARZALEX SC (daratumumab) follows as the only subcutaneous CD38-directed antibody approved to treat patients with multiple myeloma.13It binds to CD38,a surface protein highly expressed across multiple myeloma cells.14 DARZALEX induces tumor cell death through cell lysis via multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).15DARZALEX has also demonstrated immunomodulatory effects such as increasing CD4+ and CD8+ T-cells counts, which may contribute to clinical response.16

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize DARZALEX. Janssen Inc. commercializes DARZALEX and DARZALEX SC in Canada. For full Prescribing Information and more information about DARZALEX and DARZALEX SC, please visit http://www.janssen.com/canada.

About Multiple MyelomaMultiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.17 When damaged, these plasma cells rapidly spread and replace normal cells with tumors in the bone marrow. In 2020, it is estimated that 3,400 Canadians will be diagnosed with multiple myeloma and there will be 1,600 deaths associated with the disease.18 While some patients with multiple myeloma have no symptoms in the early stages, patients are diagnosed due to symptoms that can include bone disease or pain, anemia, calcium elevation, and kidney problems.19

About the Janssen Pharmaceutical Companies of Johnson & Johnson At Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.

Learn more at http://www.janssen.com/canada. Follow us at @JanssenCanada. Janssen Inc. is a member of the Janssen Pharmaceutical Companies of Johnson & Johnson.

*All trademark rights used under license. **Dr. White was not compensated for any media work. He has been compensated as a consultant.

Cautions Concerning Forward-Looking StatementsThis press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding DARZALEX SC. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Inc., any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 29, 2019, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in the company's most recently filed Quarterly Report on Form 10-Q, and the company's subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at http://www.sec.gov, http://www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

References:

1

[DARZALEX SC Product Monograph, Janssen Inc., July 29, 2020]

2

[DARZALEX SC Product Monograph, Janssen Inc., July 29, 2020]

3

Mateos MV, et al. Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial [published online ahead of print March 23, 2020]. Lancet Haematol doi.org/10.1016/S2352-3026(20)30070-3.

4

Mateos M-V et al. Efficacy and Safety of the Randomized, Open-Label, Non-inferiority, Phase 3 Study of Subcutaneous (SC) Versus Intravenous (IV) Daratumumab (DARA) Administration in Patients (pts) With Relapsed or Refractory Multiple Myeloma (RRMM): COLUMBA. 2019 American Society of Clinical Oncology Annual Meeting. June 2019.

5

Janssen Research & Development, LLC. A Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 [cited July 5, 2019]. Available at: https://clinicaltrials.gov/ct2/show/NCT03412565. Identifier: NCT03412565.

6

Mateos MV, et al. Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial [published online ahead of print March 23, 2020]. Lancet Haematol doi.org/10.1016/S2352-3026(20)30070-3.

7

Chari A, M. J., McCarthy H, et al Subcutaneous daratumumab plus standard treatment regimens in patients with multiple myeloma across lines of therapy: PLEIADES study update. Poster presented at: 61st American Society of Hematology (ASH) Annual Meeting. Orlando, FL.

8

[DARZALEX SC Product Monograph, Janssen Inc., July 29, 2020]

9

[DARZALEX SC Product Monograph, Janssen Inc.,July 29, 2020]

10

[DARZALEX SC Product Monograph, Janssen Inc., July 29, 2020]

11

Mateos MV, et al. Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial [published online ahead of print March 23, 2020]. Lancet Haematol doi.org/10.1016/S2352-3026(20)30070-3.

12

Janssen Research & Development, LLC. A Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 [cited July 5, 2019]. Available at: https://clinicaltrials.gov/ct2/show/NCT03412565. Identifier: NCT03412565.

13

Janssen Research & Development, LLC. A Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 [cited July 5, 2019]. Available at: https://clinicaltrials.gov/ct2/show/NCT03412565. Identifier: NCT03412565.

14

[DARZALEX SC Product Monograph, Janssen Inc., July 29, 2020]

15

[DARZALEX SC Product Monograph, Janssen Inc., July 29, 2020]

16

[DARZALEX SC Product Monograph, Janssen Inc., July 29, 2020]

17

Kumar, SK et al. Risk of progression and survival in multiple myeloma relapsing after therapywith IMiDs and bortezomib: a multicenter international myeloma working group study. Leukemia. 2012 Jan; 26(1):149-57.

18

Canadian Cancer Society. "Signs and Symptoms of Multiple Myeloma." Available at: https://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/statistics/?region=on.Accessed June 2020.

19

Canadian Cancer Society. "Signs and Symptoms of Multiple Myeloma." Available at: http://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/signs-and-symptoms/?region=on.Accessed June 2020.

SOURCE Janssen Inc.

For further information: Media Contact: Janssen Inc., Jennifer McCormack, Office: (416) 382-5121; Investor Contact: Jennifer McIntyre, Office: (732) 524-3922

http://www.janssen.ca/

Read the original post:
Janssen Announces Health Canada Approval of DARZALEX* SC, a New Subcutaneous Formulation for the Treatment of Patients with Multiple Myeloma - Canada...

Sernova Enters into Exclusive Worldwide License Agreement with University of Miami for Therapeutic Cell Immune Protection Technologies -…

Sernova expands its intellectual property portfolio and capabilities to develop first-in-class cell therapy solutions for type 1 diabetes and other chronic diseases that eliminate the need for life-long immunosuppression drugs

LONDON, ONTARIO - August 4, 2020 - Sernova Corp. (TSXV:SVA) (OTC:SEOVF) (FSE:PSH), a clinical-stage regenerative medicine company developing a 'functional cure' for type 1 diabetes and other chronic diseases, announced today it has entered into an exclusive, worldwide license with the University of Miami at Coral Gables, Florida, for the commercial rights to novel conformal coating immune protection technologies. The technologies were developed by Dr. Alice Tomei, Dr. Jeffrey Hubbell, and Aaron Stock (Graduate Student). Dr. Tomei is a leading international expert in immunoprotection and diabetes immunoengineering, of the renowned Diabetes Research Institute (DRI), a designated Center of Excellence at the University of Miami Miller School of Medicine. Dr. Hubbell is the Eugene Bell Professor of Tissue Engineering at the University of Chicago and leading international researcher in immunoengineering.

This exclusive worldwide license agreement is important to Sernova because it broadens the technology scope of Sernova's immune protection conformal coating technologies and related intellectual property. Furthermore, it adds to a series of recent strategic acquisitions and collaborations for the Company and builds on our goal of protecting Sernova's therapeutic cells or tissues transplanted into Sernova's Cell Pouch(TM) from a detrimental auto-immune system response while eliminating the need for immunosuppressive drugs in treated patients.

"Sernova is further advancing development of its novel Cell Pouch System(TM) as a therapeutic platform to provide cell therapy solutions to patients with chronic diseases, such as type 1 diabetes, without the current need for life-long immunosuppressive drugs. We believe, with the addition of local immune protection, our breakthrough technologies will have the potential to significantly expand access to and the availability of therapeutic solutions to millions of people as a 'functional cure' for the chronic diseases from which they are suffering," said Dr. Philip Toleikis, President and CEO of Sernova Corp.

Dr. Toleikis continued, "As we continue to advance our first-in-class technologies, we have diligently selected complementary technologies developed by recognized experts in the field such as those by Dr. Tomei and colleagues to add to our Cell Pouch(TM) platform. With the continued expansion of our regenerative medicine therapeutics platform, we are positioning the Company at the forefront in the development of safe, functional regenerative medicine therapeutics."

Dr. Alice Tomei, the Director of the Islet Immunoengineering Laboratory at DRI stated, "Following my postdoctoral training in Dr. Hubbell's laboratory at Ecole Polytechnique Federale de Lausanne, Switzerland, I joined the University of Miami where I have focussed my academic career in the pursuit and development of novel cellular immune protection technologies to advance the field of cell therapy. With Sernova's goal of a 'functional cure' for diabetes, supported by its positive preclinical and more recent, emerging clinical safety and efficacy data from the University Chicago clinical trial, I am excited to contribute to the addition of local immune protection technologies provided by conformal coatings as the next important step towards this ultimate goal."

ABOUT SERNOVA CORP.

Sernova Corp is developing regenerative medicine therapeutic solutions using a medical device (Cell Pouch(TM)) and immune protected therapeutic cells/tissues (i.e., human donor cells, corrected human cells and stem cell-derived cells) to improve the treatment and quality of life of people with chronic metabolic diseases such as insulin-dependent diabetes, blood disorders including hemophilia, and other diseases treated through cellular production of proteins or hormones missing or in short supply within the body. For more information, please visit http://www.sernova.com.

ABOUT SERNOVA'S CELL POUCH(TM) SYSTEM

The Cell Pouch(TM), as part of the Cell Pouch(TM) System, is a novel, proprietary, scalable, implantable macro- encapsulation device solution designed for the long-term survival and function of therapeutic cells. The device upon implantation is designed to incorporate with tissue, forming highly vascularized tissue chambers for the transplantation and function of therapeutic cells, which then release proteins and hormones as required to treat disease. The Cell Pouch(TM), along with therapeutic cells, has been shown to provide long-term safety and efficacy in small and large animal models of diabetes and has been proven to provide a biologically compatible environment for insulin-producing cells in humans in a Canadian first-in-human study. Sernova is currently conducting a Phase I/II study at the University of Chicago.

FOR FURTHER INFORMATION, PLEASE CONTACT:

Dominic Gray

Sernova Corp.

Tel: (519) 858-5126

dominic.gray@sernova.com

http://www.sernova.com

FORWARD-LOOKING INFORMATION

This release contains statements that, to the extent they are not recitations of historical facts, may constitute "forward-looking statements" that involve various risks, uncertainties, and assumptions, including, without limitation, statements regarding the prospects, plans, and objectives of the Company. Wherever possible, but not always, words such as "expects", "plans", "anticipates", "believes", "intends", "estimates", "projects", "potential for" and similar expressions, or that events or conditions "will", "would", "may", "could" or "should" occur are used to identify forward-looking statements. These statements reflect management's beliefs with respect to future events and are based on information currently available to management on the date such statements were made. Many factors could cause Sernova's actual results, performances or achievements to not be as anticipated, estimated or intended or to differ materially from those expressed or implied by the forward-looking statements contained in this news release. Such factors could include, but are not limited to, the Company's ability to secure additional financing and licensing arrangements on reasonable terms, or at all; ability to conduct all required preclinical and clinical studies for the Company's Cell Pouch System and/or related technologies, including the timing and results of those trials; ability to obtain all necessary regulatory approvals, or on a timely basis; ability to in-license additional complementary technologies; ability to execute its business strategy and successfully compete in the market; and the inherent risks associated with the development of biotechnology combination products generally. Many of the factors are beyond our control, including those caused by, related to, or impacted by the novel coronavirus pandemic. Investors should consult the Company's quarterly and annual filings available on http://www.sedar.com for additional information on risks and uncertainties relating to the forward-looking statements. Sernova expressly disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

More:
Sernova Enters into Exclusive Worldwide License Agreement with University of Miami for Therapeutic Cell Immune Protection Technologies -...

Fighting for a life unlimited with the Cystic Fibrosis Trust – Health Europa

Founded in 1964, the UKs Cystic Fibrosis Trust offers support and resources to patients affected by cystic fibrosis (CF), as well as funding research into treatments and the search for a cure for CF; and ensuring that CF patients can receive appropriate care and therapy. Cystic Fibrosis Trust Director of Research Dr Lucy Allen tells HEQ about the Trusts research strategy and the implications of precision treatment.

The Cystic Fibrosis Trust is the only UK charity dedicated to fighting for a life unlimited for everyone affected by CF. Cystic fibrosis is a genetic condition that affects the lungs, digestive system and other organs. It is caused by a faulty gene that controls the movement of salt and water in and out of cells, causing a buildup of thick, sticky mucus. There are more than 10,500 people living with CF in the UK; and one in 25 of us carries the faulty gene that causes it, usually without knowing. Living with CF means hours of nebulisers, physiotherapy and up to 60 tablets a day, just to stay healthy. Only half of those born with CF today are expected to live past 47 years.

Medication, physiotherapy and general health all must be considered when planning the simplest activity and being unwell can often interfere with work and education but we are fighting to overcome all those hurdles and are achieving great things through our investment in an exciting and dynamic portfolio of research and innovation. The Cystic Fibrosis Trust is the biggest charity funder of research specifically for the benefit of people with CF in the UK. New research is vital for discovering the next transformational breakthrough that will help deliver our vision of a life unlimited for all people affected by CF.

We have also established a groundbreaking Clinical Trials Accelerator Platform (CTAP) a UK-wide initiative bringing together cystic fibrosis (CF) centres, to increase participation and improve access to and delivery of high impact CF clinical trials. CTAP works with the CF community and informs them of relevant clinical trials and how they can take part in them, which is a crucial step in ensuring we get more new CF therapies and technologies to the market.

Much of this work is supported by the UK Cystic Fibrosis Registry: a secure centralised database, sponsored and managed by the Cystic Fibrosis Trust. The Registry records health data on consenting people with cystic fibrosis (CF) in England, Wales, Scotland and Northern Ireland. CF care teams enter data at every specialist centre and clinic across the UK, with over 99% of people with CF consenting to their data being submitted.

We also provide support to CF clinical teams in the NHS and support the continuous improvement of care that is provided across the UK, which is a fundamental role of the Cystic Fibrosis Trust. We also support and attract new talent into the field of CF care. The Trust provides up-to-date information, support and advice that enables even more people with CF to make the right choices for them at all stages of their lives; and our high impact campaigns for change are helping to influence key people in government and industry. Ultimately, we want everyone with CF to be in control of their own lives, and not have their conditions in control of them.

Our five-year research strategy, called putting the person into personalised medicine, was published in 2018. It sets out how our research investments will focus on research to deliver treatment and care that is tailored to everyone with cystic fibrosis (CF).

Cystic fibrosis is caused by mutations in the CFTR gene. Some effective treatments for people with specific mutations, known as precision medicines, have now been developed; and arrangements for access to the latest of these drugs, Kaftrio, are currently under discussion. For the latest updates on these ongoing discussions, please see the Life Saving Drugs area of our website at http://www.cysticfibrosis.org.uk.

These treatments could have a dramatic impact on the lives of people with CF (and have begun doing so already) by improving their life expectancy, reducing the number of lung infections and improving their quality of life. However, the era of precision medicines brings new challenges which the research strategy aims to help solve. The impact of taking these precision medicines will be different for everyone with cystic fibrosis. For example, older people with CF may have more lung damage, or complications such as CF-related diabetes (CFRD). This means that the way that their CF is managed will be unique to them, and treatments will need to reflect this. Were funding research to look at how treatments can be personalised to everyone with cystic fibrosis.

The development of precision medicines for people with CF is a huge leap forwards, but there are several reasons we shouldnt be complacent. More research is needed to determine whether CFTR modulators may be beneficial for more genotypes than they are currently approved for. To address this, we are working hard to assess whether people with other, rarer genotypes may also benefit from these drugs. Studies such as HIT-CF and research within the UK Cystic Fibrosis Innovation Hub will be important to determine this.

There is also room for improvement in the drugs that are licensed: by tweaking the drug design we could improve how they work and reduce the side effects, creating the next generation of precision medicines. To achieve this, we also need to continue lab-based biomedical research to increase our understanding of how the CFTR protein works and how it goes wrong in cystic fibrosis, and novel ways to restore its function.

Its also important to keep the interest of the drug companies involved, working with and supported by CTAP where appropriate, as they may decide to work on easier (and more profitable) disease areas if we dont. Importantly, we are still looking to develop drugs that would work for anyone with CF, whatever their genotype. This would be of particular benefit to people with rare mutations or those for whom the current drugs dont work or cause side effects.

In June of this year, we heard the exciting announcement from the European Medicines Agency (EMA) that they had found the CF drug Kaftrio safe and effective, meaning it can now progress towards being prescribed across Europe. Kaftrio is a triple-combination therapy made up of three different compounds, tezacaftor and ivacaftor (which together make up Symkevi) combined with elexacaftor.

Initially, Kaftrio is licensed for children and adults aged over 12 who have two copies of the F508del mutation, the most common CF causing mutation of the CFTR gene, or one copy of F508del and one copy of a minimal function mutation. The details of which precise genotypes the latter group covers is still to be confirmed. In addition, clinicians will be able to prescribe Kaftrio for certain patients with other rare mutations that are covered by the US Food and Drug Administrations (FDA) licensing decisions. We also expect that following completion of clinical trials, the drug licensing will expand availability to children under 12. Trials are actively being conducted in six- to 11-year-olds and the next step will be to conduct trials in children under six years old.

In clinical trials for Kaftrio, people with two copies of the F508del mutation had a 10% increase in lung function compared to treatment with Symkevi, and people with a single copy of F508del had more than a 14% increase in lung function compared to treatment with the placebo.

In England, NHS England have agreed a deal with the drugs manufacturer Vertex to facilitate access to Kaftrio from the first day the European licence is granted, which is expected to be later this summer or early autumn. Similarly, in Wales, the Health Minister also recently announced that a deal had been agreed for Kaftrio. We are continuing to work with all key stakeholders to ensure access to everyone in the UK who could benefit. In the first instance, that is seeking more information and updates about negotiations and access in Scotland, Northern Ireland, and the crown dependencies of Jersey, Guernsey, and the Isle of Man. We are also working to understand the mutations covered in the NHS England and NHS Wales deals and what flexibility clinicians will have in prescribing Kaftrio for people with rare or other mutations.

We are working with the UK Cystic Fibrosis Medical Association to support plans for rollout to ensure everyone can start Kaftrio as fast as clinically possible and we also support the UK CF Registry, which will continue its valuable work in monitoring the effectiveness of this drug, among many others.

At least three companies, including AbbVie, Proteostasis Therapeutics and Vertex Pharmaceuticals, are developing other potential triple combination therapies. Through our Clinical Trials Accelerator Platform, we are actively working to support the ongoing HIT-CF Europe research project which aims to provide better treatments for people with rare CF mutations who are currently ineligible for Kaftrio.

An important role for the CF Trust is to push the boundaries, demonstrating leadership and innovation to ensure research is excellent, timely and relevant. The ongoing development of our flagship research programmes, which include Strategic Research Centres, the Innovation Hub in CF Lung Health, the CF Syndicate in Antimicrobial Resistance, investments in digital health and CTAP, has enabled us to create a unique platform, placing the Trust in a strong position to facilitate research which addresses some of the key challenges that will confront healthcare over the next decade.

As the general population gets older, they start to become affected by a range of different diseases and conditions. The same will be true for people with cystic fibrosis. We know that people with CF may also be affected by conditions like cancer, diabetes, heart disease and social wellbeing, and perhaps in different ways to those who dont have cystic fibrosis. It is important to explore and better understand these multiple long term conditions, also a current priority for UK government, and to reduce their impact.

Rather than using drugs to correct the function of the CFTR protein, another area of research underway is looking to correct the CFTR gene itself, either by delivering healthy, non-mutated copies of the gene using gene therapy, or by correcting the existing damaged copy of the gene using gene editing. If this cutting-edge research is successful, future gene editing treatments for CF could either do on the job repairs to the cells that line the surface of the lungs, or the CF gene could be edited in cells in the lab and then corrected cells could be delivered back into the lungs. Whilst good progress is being made towards genetic-based treatments it is unlikely this will be available as a standard treatment for people with CF for many years. However, if they do become available, they could make a significant difference to everyone, irrespective of their genetic mutation.

People with CF can have a range of different lung infections, and its important to know which infections are present and how to treat them. Current post-licensing drug studies on the first of the CFTR modulators Ivacaftor showed that while people taking this modulator drug have fewer flare-ups of poor lung health and fewer infections, people are still susceptible to some infection, highlighting the importance of continuing investment in research to treat and understand lung infections in CF.

The earlier the infections are detected, the better chance there is of effectively treating them. Understanding how the bugs (bacteria, viruses and fungi) work can help researchers to identify possible druggable targets Increasingly these bugs are becoming resistant to antimicrobial therapies used to treat infections which means that better understanding and overcoming antimicrobial resistance is a key priority for CF, just as it is for public health globally.

As the lungs get more damaged, for many with CF a lung transplant may become the only treatment option, but there are sadly not enough donor lungs readily available. Researchers are investigating whether a combination of stem cell technology and gene editing could replace damaged lung cells, regenerating the lungs and providing an alternative to lung transplant.

The Cystic Fibrosis Trust supports a balanced portfolio of research, conducted within universities, private companies, hospitals and other healthcare settings around the world. The impact of the COVID-19 pandemic on Trust-funded research studies will vary on an individual study-by-study basis, and any true negative or positive impact is likely to emerge over time. As part of an ongoing dialogue with our grantees, we have put measures in place to try and protect both the research and the researchers we fund from the financial impact of COVID-19. We have encouraged all grantees to make use of the government-initiated financial support schemes where appropriate. We are also receiving regular updates on how or whether the pandemic has affected their ability to complete their research studies in a timely way.

COVID-19 has impacted on every area of life for many around the globe and has caused great deal of anxiety for many people with cystic fibrosis. In fact, many of the CF community will have been shielding to protect themselves from the risk of infection.

At the CF Trust, we are doing all we can to try and support people with CF and their families through this unprecedented time:

The UK Cystic Fibrosis Innovation Hub based at Cambridge University is a groundbreaking strategic partnership between the Cystic Fibrosis Trust and the University of Cambridge. Its aim is to harness multidisciplinary world class research to accelerate progress towards preventing lung damage in CF and subsequent loss of lung function. Its a five-year programme that began in 2018. The CF Trust aims to raise 5 million over the next five years for the Innovation Hub, which the University of Cambridge has already committed to match pound for pound to 5 million. In addition, the Innovation Hub has secured a physical presence for CF research in the new Heart and Lung Research Institute (HLRI) located close to Royal Papworth Hospital.

Increasingly CF bacterial infections are becoming resistant to these antibiotics, known as antimicrobial resistance or AMR, and it can become harder and harder to treat them. There is increasing concern worldwide about AMR; the UK Government has recently appointed the former Chief Medical Officer Dame Sally Davies as its Special Envoy on AMR, to raise its profile in the G7 and G20. Researchers within the Innovation Hub are designing new antibiotics to tackle AMR and to treat these serious CF infections from a first-principles approach. They are applying world-leading and cutting-edge methods to investigate the transmission of infection, and the biology of what makes Pseudomonas aeruginosa and Mycobacterium abscessus, two of the most aggressive bacterial infections in the CF lung, grow and survive.

They are aiming to combine all their approaches to design new, more effective antibiotics to deliver a shorter, more efficient eradication of bacteria and treatments that are harder for bacteria to develop resistance to. As many infections develop AMR, treating infections across the population is a world-wide health concern. Innovations made in tackling AMR in CF will also be applicable to solving AMR for all those with drug-resistant infections.

Dr Lucy Allen Director of Research Cystic Fibrosis Trust http://www.cysticfibrosis.org.uk

This article is from issue 14 of Health Europa. Clickhere to get your free subscription today.

Read more from the original source:
Fighting for a life unlimited with the Cystic Fibrosis Trust - Health Europa