Press Release: Novartis analysis shows crizanlizumab (SEG101) increased the number of patients free of sickle cell pain crises vs placebo during SUSTAIN study

Novartis International AG / Novartis analysis shows crizanlizumab

(SEG101) increased the number of patients free of sickle cell pain

crises vs placebo during SUSTAIN study. Processed and transmitted by

West Corporation. The issuer is solely responsible for the content of

this announcement.

-- Data published in the American Journal of Hematology show more than twice

as many patients taking crizanlizumab did not experience a

disease-related pain crisis (also called vaso-occlusive crisis, or VOC)

vs placebo

-- VOCs are the most common, painful complication of sickle cell disease and

the main reason patients seek medical care in hospitals

-- Discussions with health authorities continue; FDA filing anticipated in

2019

Basel, October 9, 2018 - Results from a post hoc analysis of the Phase

II SUSTAIN study of crizanlizumab, a humanized anti-P-selectin

monoclonal antibody being investigated for the treatment of sickle cell

disease (SCD), have been published in the American Journal of

Hematology. The analysis showed that more patients treated with

crizanlizumab did not experience a vaso-occlusive crisis (VOC) vs those

treated with placebo (35.8% vs 16.9%), specifically patients with a

history of 2-10 VOCs in the previous year.

VOCs are a painful complication of SCD and the main reason why patients

seek medical care in hospitals[1],[2]. VOCs, which are triggered by

multi-cell adhesion, are associated with increased morbidity and

mortality, and can result in stroke, as well as organ damage or

failure[3],[4]. Currently, treatment options for VOCs are limited[5].

"The unpredictable, intense painful crises that patients with sickle

cell disease experience are the hallmark of the disease and the primary

cause of hospitalizations in this patient population," said Abdullah

Kutlar, MD, Director, Sickle Cell Center at the Medical College of

Georgia, Augusta University, Augusta, Georgia, and primary author of the

SUSTAIN analysis. "I am encouraged that results from this post hoc

analysis of SUSTAIN study data found that crizanlizumab could

substantially delay or prevent these crises, which also may mean less

organ damage in the long run."

The post hoc analysis reviewed 52-week results from 132 patients,

including 67 treated with crizanlizumab 5 mg/kg and 65 who received

placebo. All evaluated patients had a history of at least 2 VOCs in the

year prior to the study, with 62.9% (n=83) having experienced 2-4 events

and 37.1% (n=49) with 5-10 events. The most common genotype in SCD,

homozygous hemoglobin S (HbSS), was identified in most SUSTAIN patients

(n=94; 71.2%), and patients with this genotype were evenly distributed

between study arms.

The analysis found that treatment with crizanlizumab may prevent VOCs,

both in patients who had 2-4 and 5-10 disease-related pain events in the

year prior to the study, as well as those with HbSS.

Of the subgroups evaluated, a considerable number of patients across

multiple subgroups treated with crizanlizumab did not experience a VOC

compared with those treated with placebo, including:

-- Those with 2-4 events in the year prior to participating in the study (17

out of 42 patients or 40.5% vs 10 out of 41 patients, or 24.4%)

-- Those with 5-10 events in the year prior to participating in the study (7

out of 25 patients or 28.0% vs 1 out of 24 patients, or 4.2%)

-- Those with the HbSS genotype (15 out of 47 patients or 31.9% vs 8 out of

47 patients, or 17.0%)

-- Those also with concomitant use of hydroxyurea (14 out of 42 patients

33.3% vs 7 out of 40 patients, or 17.5%)

No new safety concerns emerged in the post hoc analysis as adverse

events attributed to treatment were similar between the crizanlizumab

and placebo arms across all subgroups.

"The insights gained from this analysis and others from the SUSTAIN

study, strengthen our belief that crizanlizumab may become an important

new therapeutic option for sickle cell patients who continue to need

step changes in medical innovation," said Samit Hirawat, MD, Head,

Novartis Oncology Global Drug Development. "This is another example of

what we mean when we say we are reimagining medicine."

About the SUSTAIN trial

The Phase II SUSTAIN trial was a multicenter, multinational, randomized,

placebo-controlled, double-blind,12-month study to assess safety and

efficacy of the anti-P-selectin antibody crizanlizumab with or without

concomitant use of hydroxyurea therapy in sickle cell disease patients

with sickle cell-related pain crises. Primary results were published in

The New England Journal of Medicine and showed that crizanlizumab

reduced the median annual rate of sickle cell pain crises (SCPCs) by

45.3% compared to placebo (1.63 vs 2.98, p=0.010) in patients with or

without hydroxyurea therapy[6].

Adverse events that occurred in 10% or more of the patients in either

active-treatment group (2.5 mg/kg; 5 mg/kg) and at a frequency that was

at least twice as high as that in the placebo group were arthralgia,

diarrhea, pruritus, vomiting, and chest pain. There were no apparent

increases in infections with crizanlizumab treatment[6].

About crizanlizumab (SEG101)

Crizanlizumab (SEG101) is a humanized anti-P-selectin monoclonal

antibody being investigated for the prevention of vaso-occlusive crises

(VOCs) in patients with sickle cell disease (SCD)[6]. Crizanlizumab

binds a molecule called P-selectin on the surface of endothelial cells

and platelets in the blood vessels, causing a blockade of P-selectin[6].

P-selectin is one of the major drivers of the vaso-occlusive process[6].

Results from the Phase II SUSTAIN study demonstrated that crizanlizumab

reduced the median annual rate of VOCs that lead to a healthcare visit

compared to placebo in patients with SCD regardless of whether or not

they were taking hydroxyurea[6].

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," "expect," "anticipate,"

"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; our ability to obtain or maintain proprietary intellectual

property protection; the particular prescribing preferences of

physicians and patients; general political and economic conditions;

safety, quality 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 1 billion people globally

and we are finding innovative ways to expand access to our latest

treatments. About 125 000 people of more than 140 nationalities work at

Novartis around the world. Find out more at www.novartis.com.

Novartis is on Twitter. Sign up to follow @Novartis at

http://twitter.com/novartis

For Novartis multimedia content, please visit

www.novartis.com/news/media-library

For questions about the site or required registration, please contact

media.relations@novartis.com

References

[1] Puri L, Nottage KA, Hankins JS, et al. State of the art management

of acute vaso-occlusive pain in sickle cell disease. Paediatr Drugs.

2018;(1)20:29-42.

[2] Gutsaeva D, Parkerson J, Yerigenahally S, et al. Inhibition of

cell adhesion by anti-P-selectin aptamer: a new potential therapeutic

agent for sickle cell disease. Blood. 2011;117(2):727-735.

[3] Ballas SK, Gupta K, Adams-Graves P. Sickle cell pain: a critical

reappraisal. Blood. 2012:120(18):3647-3656

[4] Piel F, Steinberg M, Rees D. Sickle cell disease. N Engl J Med.

2017;376(16):1561-1573.

(MORE TO FOLLOW) Dow Jones Newswires

October 09, 2018 16:30 ET (20:30 GMT)