GlobeNewswire

Novartis Adakveo® receives positive CHMP opinion for the prevention of recurrent vaso-occlusive crises in patients with sickle cell disease

Share
  • If approved, Adakveo would be the first targeted sickle cell disease therapy available for use in Europe

  • CHMP opinion supported by data showing Adakveo significantly reduced the rate of vaso-occlusive crises, with patients on Adakveo spending fewer days in hospital

  • Vaso-occlusive crises are sudden, unpredictable, and associated with an increased risk of organ damage and mortality1

Basel, July 24, 2020 — Novartis announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending conditional marketing authorization of Adakveo® (crizanlizumab) for the prevention of recurrent vaso-occlusive crises (VOCs), or pain crises, in patients with sickle cell disease aged 16 years and older. Adakveo can be given as an add-on therapy to hydroxyurea/hydroxycarbamide (HU/HC) or as monotherapy in patients for whom HU/HC is inappropriate or inadequate.

“Sickle cell disease is a lifelong and devastating condition that affects patients, families and communities,” said Professor Jo Howard, Professor in Haemoglobinopathies,
Guy's and St Thomas' NHS Foundation Trust in London. “Today’s positive opinion by CHMP means that we are one step closer to potentially having an important new medicine to treat thousands of vulnerable patients.”

If approved by the European Commission, Adakveo will be the first targeted medicine available in Europe for the prevention of VOCs in patients with sickle cell disease. Adakveo binds to P-selectin – a cell adhesion protein that plays a central role in the multicellular interactions that can lead to vaso-occlusion.2,3 Though considered a rare condition, tens of thousands of people in Europe have sickle cell disease.4,5

“The positive CHMP opinion for Adakveo underscores the potential of this new medicine to prevent recurrent sickle cell pain crises, which can affect all aspects of patients’ lives,” said Susanne Schaffert, PhD, President, Novartis Oncology. “Novartis is dedicated to innovation where there is significant unmet need, and we are grateful for the support we have received from the community of sickle cell patients, advocates and medical experts in Europe and around the world who continue to help us reimagine medicine for this devastating disease.” 

The CHMP opinion was based on results of the 52-week, randomized, placebo-controlled SUSTAIN trial, which showed that Adakveo significantly lowered the median annual rate of VOCs to 1.63 vs 2.98 compared to placebo (P=.010), equivalent to a 45% reduction. Reductions in the frequency of VOCs were observed among patients regardless of sickle cell disease genotype and/or hydroxyurea use.6

Additional results from the SUSTAIN study include:

  • A decrease in the median annual rate of days hospitalized to 4 vs 6.87 days when compared with placebo (a 42% reduction)
  • Median time to first VOC, 4.1 months for Adakveo vs 1.4 months for placebo                         

The European Commission reviews the CHMP recommendation and usually delivers its final decision in approximately two months. In addition, the Committee for Orphan Medicinal Products is currently reviewing the maintenance of the orphan designation of Adakveo. Adakveo is currently approved in the United States and seven other countries for reducing the frequency of vaso-occlusive crises in patients with sickle cell disease aged 16 years and older.

About Sickle Cell Disease
Sickle cell disease is one of the most common genetic blood disorders in the world.7 It is a chronic, lifelong, debilitating disease that can range in clinical severity.1 It affects the shape of the red blood cells and can make blood cells stickier than usual.8 When blood cells stick to one another they can form clusters in the bloodstream.9,10 These clusters can block and reduce the flow of blood and oxygen and can cause damage to the blood vessels and organs.1,11 When blood cell clusters get big enough, they can block and slow blood flow that can lead to unpredictable painful crises, also referred to as vaso-occlusive crises.1 Sickle cell pain crises disrupt patients’ lives physically, socially, and emotionally – and can worsen into acute and long-term complications.12

People living with sickle cell disease inherited two sickle cell genes from their parents.8 Those who have the sickle cell trait inherited one sickle cell gene and one normal gene.8 The sickle cell trait can be asymptomatic, but individuals with the disease can pass the trait on to their children.9 If both parents have the trait, individuals have a 25% chance of having sickle cell disease, a 50% chance of having sickle cell trait and a 25% chance of having two normal genes or of having neither sickle cell trait or sickle cell disease.13 A simple blood test can identify whether a person is a carrier of the sickle cell trait.13

Sickle cell disease impacts many different populations around the world, but disproportionately affects people from sub-Saharan Africa.7 It also is common among people with ancestry from South America, Central America, and India, as well as several Mediterranean countries, such as Italy and Turkey, and other populations.7

About Adakveo
Adakveo® (crizanlizumab) – previously known as SEG101 – is indicated for the prevention of recurrent VOCs in sickle cell patients aged 16 years and older. It can be given as an add-on therapy to HU/HC or as monotherapy in patients for whom HU/HC is inappropriate or inadequate. It is the first and only targeted biologic that works by binding to P-selectin, a cell adhesion protein that plays a central role in the multicellular interactions that can lead to vaso-occlusion in sickle cell disease.

By binding to P-selectin on the surface of the activated endothelium and platelets, Adakveo blocks interactions between endothelial cells, platelets, red blood cells, and leukocytes.

About SUSTAIN
SUSTAIN is a randomized, multicenter, placebo-controlled, double-blind study. A total of 198 sickle cell disease patients aged 16 to 63 years (inclusive; mean age 30.1±10.3 years), with any sickle cell disease genotype (including HbSS [71.2%], HbSC [16.2%], HbSbeta0‑thalassaemia [6.1%], HbSbeta+‑thalassaemia [5.1%], and others [1.5%]) and a history of between 2 and 10 VOCs in the previous 12 months (62.6% and 37.4% of the patients had 2‑4 or 5‑10 VOCs, respectively), were randomized 1:1:1 to Adakveo 5 mg/kg, Adakveo 2.5 mg/kg or placebo. The majority of patients were Black or African American (91.9%). Patients received Adakveo with (62.1%) or without (37.9%) HU/HC. Randomization was stratified by patients already receiving HU/HC (Y/N) and by number of VOCs in the previous 12 months (2 to 4, 5 to 10). Patients were allowed to take medicinal products to relieve pain (i.e. paracetamol, NSAIDs and opioids) and to receive occasional transfusions on an “as needed” basis. Patients participating in a chronic transfusion program (pre-planned series of transfusions for prophylactic purposes) were excluded from the study.

Treatment with Adakveo 5 mg/kg resulted in a 45.3% lower median annual rate of VOCs compared to placebo (Hodges‑Lehmann, median absolute difference of ‑1.01 compared with placebo, 95% CI [‑2.00, 0.00]), which was statistically significant (p=0.010). The median annual rates of uncomplicated VOCs (any VOCs as defined above, excluding acute chest syndrome, hepatic sequestration, splenic sequestration, or priapism) and days hospitalized were 62.9% and 41.8% lower in the Adakveo 5 mg/kg than in the placebo group, respectively. The VOCs occurring during the study were assessed by an independent review committee.

Important Safety Information
Adakveo may cause serious side effects, including infusion-related reactions. Infusion-related reactions may happen within 24 hours of receiving an infusion of Adakveo. Patients should tell their doctor or nurse immediately if they experience any of the following, which may be signs and symptoms of an infusion-related reaction, such as fever, chills or shivering, nausea, vomiting, tiredness, dizziness, sweating, hives, itching, or shortness of breath or wheezing. In the event of a severe reaction, crizanlizumab should be discontinued and appropriate therapy should be instituted.

The most common side effects (incidence > 10%) were arthralgia, nausea, back pain, pyrexia, and abdominal pain. Other side effects which may affect up to 1 in every 10 people are diarrhea, itching (including vulvovaginal itching), vomiting, muscle pain (myalgia), pain in the muscles or bones of the chest (musculoskeletal chest pain), sore throat (oropharyngeal pain), and redness or swelling and pain at the site of the infusion.

Adakveo may interfere with a laboratory test used to measure the number of platelets in the blood. Patients should tell their doctor or nurse that they are on treatment with Adakveo. It is recommended to run the tests as soon as possible (within 4 hours of blood collection) or use tubes containing citrate.

It is preferable to avoid the use of Adakveo during pregnancy and in woman of childbearing potential not using contraception.

Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “seek,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis
Novartis is reimagining medicine to improve and extend people’s lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. Novartis products reach nearly 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 110,000 people of more than 145 nationalities work at Novartis around the world. Find out more at
https://www.novartis.com.

Novartis is on Twitter. Sign up to follow @Novartis at https://twitter.com/novartisnews
For Novartis multimedia content, please visit https://www.novartis.com/news/media-library
For questions about the site or required registration, please contact media.relations@novartis.com

References
1. Steinberg M. Management of sickle cell disease. N Engl J Med. 1999;340(13):1021-1030.
2. Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010;376(9757):2018-2031.
3. Lawrence MB, Springer TA. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell. 1991;65(5):859-873.
4. European Medicines Agency. Crizanlizumab Orphan Designation. August 2012. Available from: https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3121034
5. Roberts I, de Montalambert M. Sickle Cell disease as a paradigm of immigration haematology: new challenges for hematologists in Europe. Haematologica. 2007;92(7):865-71.
6. Ataga KI, Kutlar A, Kanter J et al. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med. 2017;376(5):429-439
7. Jain D, Lothe A, Roshan C. Sickle cell disease: current challenges. Journal of Hematology & Thromboembolic Diseases. 2015 Nov 10. Doi: 10.4172/2329-8790.1000224.
8. Gallo A, Wilkie D, Suarez M, et al. Reproductive decisions in people with sickle cell disease or sickle cell trait. NIH Public Access. 2010;32(8):1073-1090.
9. Piel F, Steinberg M, Rees D. Sickle cell disease. N Engl J Med. 2017;376(16):1565.
10. Yawn B, Buchanan G, Afenyi-Annan A, et. Management of sickle cell disease summary of the 2014 evidence-based report by expert panel members. JAMA. 2014;312(10):1033-1048.
11. Gutsaeva D, Parkerson J, Yerigenahally S, et. Inhibition of cell adhesion by anti–P-selectin aptamer: a new potential therapeutic agent for sickle cell disease. Blood. 2011;117(2):727-735.
12. Adegbola M, Barnes D, Opollo J, et. Voices of adults living with sickle cell disease pain. J Natl Black Nurses Assoc. 2012;23(2):16-23.
13. NHLBI. What is sickle cell disease?. Last updated: August 2, 2016. Available from: http://www.nhlbi.nih.gov/health/health-topics/topics/sca.

# # #

Novartis Media Relations
E-mail: media.relations@novartis.com

Anja von Treskow
Novartis Global Media RelationsMichael Billings
+41 61 324 2279 (direct)Novartis Division Communications
+41 79 392 8697 (mobile)+1 862 778 8656 (direct)
anja.von_treskow@novartis.com+1 201 400 1854 (mobile)
michael.billings@novartis.com
Eric Althoff
Novartis External Communications
+1 646 438 4335
eric.althoff@novartis.com

Novartis Investor Relations
Central investor relations line: +41 61 324 7944
E-mail: investor.relations@novartis.com

CentralNorth America
Samir Shah+41 61 324 7944Sloan Simpson+1 862 778 5052
Thomas Hungerbuehler  +41 61 324 8425
Isabella Zinck+41 61 324 7188

About GlobeNewswire

GlobeNewswire
GlobeNewswire
One Liberty Plaza - 165 Broadway
NY 10006 New York

https://globenewswire.com

GlobeNewswire is one of the world's largest newswire distribution networks, specializing in the delivery of corporate press releases financial disclosures and multimedia content to the media, investment community, individual investors and the general public.

Subscribe to releases from GlobeNewswire

Subscribe to all the latest releases from GlobeNewswire by registering your e-mail address below. You can unsubscribe at any time.

Latest releases from GlobeNewswire

AND (Ticker: AND.AS) intends to rebrand the company22.9.2020 18:05:00 CESTPress release

Supporting the turnaround and the new strategic direction of the company Capelle aan den IJssel, the Netherlands, 22 September 2020 - AND is happy to announce that it intends to change the company name and refresh its branding in Q4 2020. This change is designed to highlight the company’s new strategic direction as well as support and strengthen the transformation into a subscription based provider of premium location aware content and services. As announced on August 12th, the turnaround strategy has already delivered 22% revenue growth in the first half of 2020. AND believes the new company name and branding will help to drive continued revenue growth and put location-intelligence squarely at the center of the company’s profile. Further announcements will follow in Q4 2020. Ends About AND AND is an innovative location-aware content and service provider. Our focus is to create and deliver market leading, relevant, innovative and tailored content which fosters a safer and more sustaina

Wolters Kluwer Completes Divestment of ComplyTrack22.9.2020 17:30:00 CESTPress release

Wolters Kluwer Completes Divestment of ComplyTrack September 22, 2020 - Wolters Kluwer announces today that it has completed the divestment of ComplyTrack to symplr, as originally announced on September 8, 2020. About Wolters Kluwer Wolters Kluwer (WKL) is a global leader in professional information, software solutions, and services for the healthcare; tax and accounting; governance, risk and compliance; and legal and regulatory sectors. We help our customers make critical decisions every day by providing expert solutions that combine deep domain knowledge with specialized technology and services. Wolters Kluwer reported 2019 annual revenues of €4.6 billion. The group serves customers in over 180 countries, maintains operations in over 40 countries, and employs approximately 19,000 people worldwide. The company is headquartered in Alphen aan den Rijn, the Netherlands. Wolters Kluwer shares are listed on Euronext Amsterdam (WKL) and are included in the AEX and Euronext 100 indices. Wolt

Joint Stock Company “Olainfarm” Extraordinary Shareholders Meeting on September 22, 2020 at 15.00  has not been held due to lack of quorum22.9.2020 14:20:00 CESTPress release

Joint Stock Company “Olainfarm” Extraordinary Shareholders Meeting on September 22, 2020 at 15.00 has not been held due to lack of quorum Joint Stock Company “Olainfarm” Management Board informs that for the Extraordinary Shareholders Meeting on September 22, 2020 at 15.00 pm shareholders who in total represented 3 877 425 voting shares or 27.53% of voting capital were registered, therefore shareholders' meeting did not take place due to lack of quorum. Olaine, September 22, 2020 Additional information: Jānis Dubrovskis Investor Relations Advisor of JSC Olainfarm Ph.: +371 29178878 janis.dubrovskis@olainfarm.com

RESOLUTIONS of the Annual General Meeting of Shareholders of JSC „Olainfarm” to be held on September 22, 202022.9.2020 13:05:00 CESTPress release

RESOLUTIONS of the Annual General Meeting of Shareholders of JSC „Olainfarm” to be held on September 22, 2020 Report of the Board on results of operations in 2019. Resolution: To take notice of the Report of the Board of the JSC “Olainfarm” on results of operations in 2019. Voting results: decision is taken with the required majority of votes. Report of the Council on results of operations in 2019. Resolution: To take notice of the Report of the Council of the JSC “Olainfarm” on results of operations in 2019. Voting results: decision is taken with the required majority of votes. Approval of the JSC “Olainfarm” Consolidated Annual Report for 2019. Resolution: To approve the Consolidated and Parent Company’s Annual Report of JSC „Olainfarm” for 2019 with profit in amount of EUR 22 239 000,00. Voting results: decision is taken with the required majority of votes. Distribution of profit of 2019. Resolution: 4.1. To pay dividends to the shareholders of the Joint Stock Company" Olainfarm " i

ProMIS Neurosciences to develop multivalent vaccine for Alzheimer’s disease22.9.2020 12:30:10 CESTPress release

Potential vaccine to incorporate ProMIS proprietary peptide antigens; early in vivo preclinical data demonstrate neuronal protection and improvement in cognitive deficits TORONTO and CAMBRIDGE, Mass., Sept. 22, 2020 (GLOBE NEWSWIRE) -- ProMIS Neurosciences, Inc. (TSX: PMN) (OTCQB: ARFXF), a biotechnology company focused on the discovery and development of antibody therapeutics targeting toxic oligomers implicated in the development of neurodegenerative diseases, announced today initiation of a program to construct and test a multivalent peptide vaccine for Alzheimer’s disease (AD). The critical first steps in vaccine development will be carried out by VIDO-InterVac, a global leader in vaccine research and development. Recent progress in the development of blood-based biomarkers for neurodegeneration is enabling increased screening to diagnose and identify individuals at risk of developing AD. A vaccine capable of inducing an effective antibody response against amyloid-beta toxic oligom

AIR Worldwide Releases Updated Multiple Peril Crop Insurance Model for China22.9.2020 12:11:10 CESTPress release

Boston, Sept. 22, 2020 (GLOBE NEWSWIRE) -- Catastrophe risk modeling firm AIR Worldwide (AIR) today announced that it released an updated Multiple Peril Crop Insurance (MPCI) Model for China to support probabilistic assessments for five newly modeled crop lines of business and a newly modeled sub-peril. This update also includes a new livestock module that adds six additional lines of business and two new sub-perils. AIR Worldwide is a Verisk (Nasdaq:VRSK) business. “In 2011, AIR leveraged its considerable experience and success in modeling MPCI portfolios in the United States to develop a model for mainland China. Since then, the model has been updated several times to keep it current with the fast-changing Chinese agricultural insurance market,” said Dr. Jeff Amthor, assistant vice president, AIR Worldwide. “The MPCI Model for China captures the severity, frequency, and location of drought, flood, wind, frost, and heat events nationwide, covering over 90% of the weather-related crop