Novartis announces data showing Jakavi® (ruxolitinib) more effective than best available therapy in acute graft-versus-host disease

• Data from Phase III REACH2 study, published in The New England Journal of Medicine, demonstrate Jakavi can improve outcomes for patients with acute graft-versus-host disease (GvHD) who do not respond to first-line steroid treatment¹
   
• Results show 62% overall response rate with Jakavi at Day 28, the primary endpoint of the study, compared to 39% for best available therapy¹
   
• GvHD is a serious and common complication of allogeneic stem cell transplants with a one-year death rate as high as 80% in its acute form^2-4

Basel, April 22, 2020 — Data from the Phase III REACH2 study published today in The New England Journal of Medicine show Jakavi^® (ruxolitinib) improves outcomes across a range of efficacy measures in patients with steroid-refractory acute graft-versus-host disease (GvHD) compared to best available therapy (BAT). The results of REACH2, the first Phase III study in acute GvHD to have met its primary endpoint, reinforce findings of the previously reported Phase II REACH1 study. The new data was also selected for presentation at the Presidential Symposium of the European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting, to be held 30 August to 2 September in Madrid.

In REACH2, patients treated with Jakavi experienced significantly greater overall response rate (ORR) vs. BAT (62% vs. 39%; p<0.001) at Day 28, the primary endpoint of the study. For the key secondary endpoint, patients treated with Jakavi maintained significantly higher durable ORR (40% vs. 22%; p<0.001) at eight weeks. Additionally, Jakavi was associated with longer median failure free survival (FFS) than BAT (5.0 months vs. 1.0 months; hazard ratio 0.46, 95% CI, 0.35 to 0.60), and showed a positive trend with other secondary endpoints, including duration of response¹.

"Patients with acute graft-versus-host disease face life-threatening challenges with limited treatment options, particularly for the nearly half of individuals who do not respond to initial steroid therapy,” said Robert Zeiser, University Hospital Freiburg, Department of Haematology, Oncology and Stem Cell Transplantation, Freiburg, Germany. "These new data from REACH2 showing superiority of Jakavi over current standard-of-care therapies add to a growing body of evidence on how targeting the JAK pathway can be an effective strategy in this difficult-to-treat condition.”

No new safety signals were observed in REACH2, and adverse events (AEs) attributable to treatment were consistent with the known safety profile of Jakavi. The most common AEs were thrombocytopenia, anemia and cytomegalovirus infection. While 38% and 9% of patients required Jakavi and BAT dose modifications, respectively, the number of patients who discontinued treatment due to AEs was low (11% and 5%, respectively)¹.

"Compelling results from REACH2, the first successful randomized Phase III trial in patients with steroid-refractory acute graft-versus-host-disease, give us confidence in the potential of Jakavi to confront this difficult condition," said John Tsai, Head Global Drug Development and Chief Medical Officer, Novartis. "We look forward to initiating discussions with ex-US regulatory authorities.”

In 2019, the US Food and Drug Administration approved ruxolitinib (marketed by Incyte Corporation in the U.S. as Jakafi^®) for the treatment of steroid-refractory acute GvHD in adult and pediatric patients 12 years and older based on results of the single arm Phase II REACH1 trial⁵. The Phase III REACH3 study in patients with steroid-refractory chronic GvHD is ongoing and results are expected in the second half of this year.

About Jakavi^® (ruxolitinib)
Jakavi (ruxolitinib) is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases. Jakavi is approved by the European Commission for the treatment of adult patients with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea and for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (MF) (also known as chronic idiopathic MF), post-polycythemia vera MF or post-essential thrombocythemia MF. Jakavi is approved in 101 countries for patients with MF, including EU countries, Switzerland, Canada, Japan and in more than 75 countries for patients with PV, including EU countries, Switzerland, Japan and Canada. The exact indication for Jakavi varies by country. Additional worldwide regulatory filings are underway in MF and PV.

Novartis licensed ruxolitinib from Incyte Corporation for development and commercialization outside the United States. Ruxolitinib is marketed in the United States by Incyte Corporation as Jakafi^® for patients with PV who have had an inadequate response to or are intolerant of hydroxyurea, for patients with intermediate or high-risk MF, and steroid-refractory acute GvHD in adult and pediatric patients 12 years and older⁵.

The recommended starting dose of Jakavi in PV is 10 mg given orally twice daily. The recommended starting dose of Jakavi in MF is 15 mg given orally twice daily for patients with a platelet count between 100,000 cubic millimeters (mm) and 200,000 mm, and 20 mg twice daily for patients with a platelet count of >200,000 mm. Doses may be titrated based on safety and efficacy. There is limited information to recommend a starting dose for MF and PV patients with platelet counts between 50,000/mm and <100,000/mm. The maximum recommended starting dose in these patients is 5 mg twice daily, and patients should be titrated cautiously⁵.

Jakavi is a registered trademark of Novartis AG in countries outside the United States. Jakafi is a registered trademark of Incyte Corporation. The safety and efficacy profile of Jakavi has not yet been established outside of its approved indications.

Jakavi Important Safety Information for Treatment of Myelofibrosis (MF) and Polycythemia Vera (PV)
Jakavi can cause serious side effects, including a decrease in blood cell count and infections. Complete blood count monitoring is recommended. Dose reduction or interruption may be required in patients with any hepatic impairment or severe renal impairment or in patients developing hematologic adverse reactions such as thrombocytopenia, anemia and neutropenia. Dose reductions are also recommended when Jakavi is co-administered with strong CYP3A4 inhibitors or fluconazole. Use of Jakavi during pregnancy is not recommended, and women should avoid becoming pregnant during Jakavi therapy. Women taking Jakavi should not breast feed. Progressive multifocal leukoencephalopathy (PML) has been reported. Physicians should be alert for neuropsychiatric symptoms suggestive of PML. Hepatitis B viral load (HBV-DNA titer) increases have been reported in patients with chronic HBV infections. Patients with chronic HBV infection should be treated and monitored according to clinical guidelines. Non-melanoma skin cancer (NMSC) has been reported in Jakavi treated patients. Periodic skin examination is recommended. Very common adverse reactions in MF (>10%) include urinary tract infections, anemia, thrombocytopenia, neutropenia, hypercholesterolemia, dizziness, headache, alanine aminotransferase increased, aspartate aminotransferase increased, bruising and weight gain. Common adverse reactions in MF (1 to 10%) include herpes zoster and flatulence. Uncommon adverse reactions in MF include tuberculosis. Very common adverse reactions in PV (>10%) include anemia, thrombocytopenia, hypercholesterolemia, hypertriglyceridemia, dizziness, alanine aminotransferase increased and aspartate aminotransferase increased. Common adverse reactions in PV (1 to 10%) include urinary tract infections, herpes zoster, weight gain, constipation and hypertension.

Please see full Prescribing Information available at www.jakavi.com.

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.

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References

1. Robert Zeiser, M.D., et al. Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease. New England Journal of Medicine. 2020.
2. Von Dalowski F, et al. Mesenchymal Stromal Cells for Treatment of Acute Steroid-Refractory Graft Versus Host Disease: Clinical Responses and Long-Term Outcome. Stem Cells, 2016 34(2): 357-366. doi.org/10.1002/stem.2224 
3. Shapira MY, et al. Regional intra-arterial steroid treatment in 120 patients with steroid-resistant or -dependent GvHD. Bone Marrow Transplant. 2017 52(10): 1416-1422. doi.org/10.1038/bmt.2017.120
4. Pidala J, et al. Mycophenolate mofetil for the management of steroid-refractory acute graft vs host disease. Bone Marrow Transplant. 2010 45(5): 919-924. doi.org/10.1038/bmt.2009.252
5. Jakavi^® (ruxolitinib) tablets: EU Summary of Product Characteristics. Novartis; Mar 2015.

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