On February 8, 2022 Incyte (Nasdaq:INCY) reported that 2021 fourth quarter financial results, provides 2022 financial guidance and a status update on the Company’s clinical development portfolio (Press release, Incyte, FEB 8, 2022, View Source [SID1234607849]).
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"2021 was a year of important accomplishments for Incyte. Growth of product and royalty revenues was strong, led by robust demand for Jakafi (ruxolitinib), continued uptake of Pemazyre (pemigatinib) in the U.S., and a rapidly growing royalty revenue stream. Throughout the year, we significantly expanded our commercial portfolio with several new approvals, including Pemazyre (pemigatinib) in cholangiocarcinoma (CCA) in Europe and Japan; Minjuvi (tafasitamab) in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in Europe; and, in the U.S., both Jakafi in steroid-refractory chronic graft-versus-host disease (GVHD) and Opzelura (ruxolitinib) cream in atopic dermatitis," said Hervé Hoppenot, Chief Executive Officer, Incyte. "Our launch of Opzelura has been very successful thus far. Nearly 19,000 patients were treated in the fourth quarter and feedback from both dermatologists and patients has been very positive. Importantly, we have also made significant progress towards ensuring optimal patient access to Opzelura."
Portfolio Updates
MPNs and GVHD – key highlights
Axatilimab (anti-CSF-1R monoclonal antibody) in chronic GVHD: In December, updated positive data from the Phase 1/2 trial evaluating axatilimab as a monotherapy in patients with recurrent or refractory chronic GVHD despite two or more prior lines of therapy were presented at ASH (Free ASH Whitepaper). A 68% overall response rate and broad clinical benefit across multiple organs were observed at doses being assessed in the pivotal AGAVE-201 trial. Additional trials of axatilimab are planned in patients with steroid-refractory chronic GVHD, including a Phase 2 trial in combination with a JAK inhibitor.
LIMBER (Leadership In MPNs BEyond Ruxolitinib) program: The new drug application (NDA) for once-daily ruxolitinib (QD) is on track for submission in the first half of this year. Two Phase 3 trials of ruxolitinib in combination with parsaclisib as a first-line therapy for patients with MF and as a therapy for MF patients with a suboptimal response to ruxolitinib monotherapy are both underway. Combination trials of ruxolitinib with INCB57643 (BET) and INCB00928 (ALK2) are in preparation with initial data expected later this year.
Indication and status
QD ruxolitinib
(JAK1/JAK2)
Myelofibrosis, polycythemia vera and GVHD: clinical pharmacology studies
ruxolitinib + parsaclisib
(JAK1/JAK2 + PI3Kδ)
Myelofibrosis: Phase 3 (first-line therapy) (LIMBER‑313)
Myelofibrosis: Phase 3 (suboptimal responders to ruxolitinib) (LIMBER‑304)
ruxolitinib + INCB57643
(JAK1/JAK2 + BET)
Myelofibrosis: Phase 2 in preparation
ruxolitinib + INCB00928
(JAK1/JAK2 + ALK2)
Myelofibrosis: Phase 2 in preparation
ruxolitinib + CK08041
(JAK1/JAK2 + CB-Tregs)
Myelofibrosis: PoC in preparation
itacitinib (JAK1)
Treatment-naïve chronic GVHD: Phase 2/3 (GRAVITAS‑309)
axatilimab (anti-CSF-1R)2
Chronic GVHD (third-line plus therapy): Pivotal Phase 2 (AGAVE-201)
1 Development collaboration with Cellenkos, Inc.
2 Clinical development of axatilimab in GVHD conducted in collaboration with Syndax Pharmaceuticals.
Other Hematology/Oncology – key highlights
Parsaclisib in warm autoimmune hemolytic anemia (wAIHA): Following positive Phase 2 results, a Phase 3 randomized trial evaluating the efficacy and safety of parsaclisib in adults with wAIHA has been initiated. There are currently no FDA approved treatments for wAIHA in the United States, and there are approximately 1 in 8,000 patients living with wAIHA, of which 30% are treatable.
Parsaclisib in non-Hodgkin lymphomas: In January, Incyte announced the withdrawal of the New Drug Application (NDA) in the United States for parsaclisib for the treatment of patients with relapsed or refractory follicular lymphoma (FL), marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL). The decision to withdraw the NDA followed discussions with U.S. Food and Drug Administration (FDA) regarding confirmatory studies that Incyte determined cannot be completed within a reasonable period to support an accelerated approval. The withdrawal of the NDA is a business decision and is not related to any changes in either the efficacy or safety of parsaclisib. The decision impacts only the FL, MZL and MCL indications in the U.S., and does not affect other ongoing clinical trials in the U.S. or other countries. An MAA submission for parsaclisib in MZL is under review with the EMA.
Indication and status1
pemigatinib
(FGFR1/2/3)
CCA: Phase 3 (FIGHT‑302)
Myeloid/lymphoid neoplasms (MLN): Phase 2 (FIGHT‑203)
Glioblastoma: Phase 2 in preparation
NSCLC: Phase 2 in preparation
tafasitamab
(CD19)2
Relapsed or refractory DLBCL: Phase 2 (L-MIND); Phase 3 (B-MIND)
First-line DLBCL: Phase 3 (frontMIND)
Relapsed or refractory FL and Relapsed or refractory MZL: Phase 3 (inMIND)
Relapsed or refractory B-cell malignancies: PoC (topMIND) with parsaclisib (PI3Kδ)
Relapsed or refractory B-cell malignancies: PoC with lenalidomide and plamotamab in preparation3
parsaclisib
(PI3Kδ)
Autoimmune hemolytic anemia: Phase 3 (PATHWAY)
retifanlimab
(PD‑1)4
SCAC: Phase 3 (POD1UM‑303)
MSI-high endometrial cancer: Phase 2 (POD1UM‑101, POD1UM‑204)
Merkel cell carcinoma: Phase 2 (POD1UM‑201)
NSCLC: Phase 3 (POD1UM‑304)
1 CCA = cholangiocarcinoma; DLBCL = diffuse large B-cell lymphoma; SCAC = squamous cell anal carcinoma; FL = follicular lymphoma; MZL = marginal zone lymphoma; MCL = mantle cell lymphoma; CLL = chronic lymphocytic leukemia
2 Development of tafasitamab in collaboration with MorphoSys.
3 Clinical collaboration with MorphoSys and Xencor, Inc. to investigate the combination of tafasitamab plus lenalidomide in combination with Xencor’s CD20xCD3 XmAb bispecific antibody, plamotamab.
4 Retifanlimab licensed from MacroGenics.
Inflammation and Autoimmunity (IAI) – key highlights
Dermatology
Opzelura launch in AD in the U.S.: In October, Incyte launched its first dermatology product with the FDA approval of Opzelura, a novel cream formulation of Incyte’s selective JAK1/JAK2 inhibitor ruxolitinib, in AD. Nearly 19,000 new patients started Opzelura in the fourth quarter and feedback from dermatologists and patients has been very positive with efficacy, and in particular the rapid onset and itch reduction, as a top reason for prescribing.
Ruxolitinib cream in vitiligo in the U.S. and Europe: In December, Incyte announced the FDA accepted for Priority Review the supplemental New Drug Application (sNDA) for ruxolitinib cream 1.5% (Opzelura) as a potential treatment for adolescents and adults (age ≥12 years) with vitiligo. The Prescription Drug User Fee Act (PDUFA) target action date is April 18, 2022. The Marketing Authorization Application (MAA) is under review at the European Medicines Agency (EMA). Vitiligo represents the second substantial opportunity for Opzelura, an indication where there are no approved therapies for repigmentation. There are over 1.5 million patients living with vitiligo in the United States and over 2 million in Europe.
Ruxolitinib cream in pediatric AD: A Phase 3 randomized trial (TRuE-AD3) evaluating the efficacy and safety of ruxolitinib cream in children ages two to twelve years old with AD is currently ongoing.
Ruxolitinib cream in chronic hand eczema (CHE): Incyte continues to expand the development of ruxolitinib cream into new indications as part of its life cycle management strategy. A Phase 3 trial evaluating ruxolitinib cream in chronic hand eczema is being initiated.
INCB54707 (JAK1) in multiple dermatology indications: Incyte’s growing dermatology portfolio includes INCB54707, a JAK1 specific inhibitor, which is being evaluated across multiple indications. Phase 2 trials are currently ongoing in vitiligo, hidradenitis suppurativa and prurigo nodularis, with data in vitiligo and hidradenitis suppurativa expected later this year.
Indication and status
ruxolitinib cream1
(JAK1/JAK2)
Atopic dermatitis: Phase 3 pediatric study (TRuE-AD3)
Vitiligo: Phase 3 (TRuE-V1, TRuE-V2, primary endpoint met in both studies); sNDA under Priority Review and MAA under review
Chronic hand eczema: Phase 3 (TRuE-CHE1) being initiated
INCB54707 (JAK1)
Hidradenitis suppurativa: Phase 2b
Vitiligo: Phase 2
Prurigo nodularis: Phase 2
1 Novartis’ rights for ruxolitinib outside of the United States under our Collaboration and License Agreement with Novartis do not include topical administration.
Discovery and early development – key highlights
Incyte’s portfolio of other earlier-stage clinical candidates is summarized below.
Oral PD-L1 Program: In November, Incyte presented data from a Phase 1 study evaluating INCB86550, the first in a series of oral PD-L1 inhibitors in the clinic. INCB86550 is the first oral PD-L1 inhibitor to demonstrate clinical efficacy. Early data were presented for INCB99280 and INCB99318, two other oral PD-L1 inhibitors which are also in the clinic.
MCLA-145 (CD137/PD-L1 bispecific antibody): In January, Incyte announced the decision to opt-out of the continued development of MCLA-145 as part of its ongoing portfolio prioritization and capital allocation review. Incyte will continue to collaborate with Merus and leverage their platform to develop a pipeline of novel agents, as the Company continues to hold worldwide development and commercialization rights to up to ten additional programs.
Modality
Candidates
Small molecules
INCB81776 (AXL/MER), epacadostat (IDO1), INCB86550 (PD-L1), INCB99280 (PD-L1), INCB99318 (PD-L1), INCB106385 (A2A/A2B)
Monoclonal antibodies1
INCAGN1876 (GITR), INCAGN2385 (LAG‑3), INCAGN1949 (OX40), INCAGN2390 (TIM‑3), INCA00186 (CD73)
1 Discovery collaboration with Agenus.
Partnered – key highlights
Baricitinib in alopecia areata (AA): Regulatory applications for baricitinib as a treatment for alopecia areata have been submitted in the U.S., Europe and Japan. Submissions were based on results from two pivotal Phase 3 trials (BRAVE-AA1 and BRAVE-AA2), which found once-daily baricitinib 4-mg was superior to placebo in achieving significant scalp hair regrowth as early as 24 weeks in adults with severe AA as defined by ≥50% scalp hair loss at baseline. Baricitinib has the potential to be a first-in-disease treatment for the millions of adults worldwide living with AA.
Baricitinib in AD in the U.S.: In January, Incyte and Lilly provided a regulatory update on the sNDA for baricitinib in AD. Based on ongoing discussions with the FDA, Lilly announced that alignment on the indicated population had not yet been reached and given the FDA’s position, there would be the possibility of a Complete Response Letter (CRL).
Baricitinib in systemic lupus erythematosus (SLE): In January, Incyte and Lilly announced the discontinuation of the Phase 3 development program for baricitinib in SLE based on top-line efficacy results from two pivotal Phase 3 trials (SLE-BRAVE-I and –II). The primary endpoint of SRI-4 response was reached in SLE-BRAVE-I but was not reached in SLE-BRAVE-II and key secondary endpoints were not met in either study.
Indication and status
ruxolitinib (JAK1/JAK2)1
Acute and chronic GVHD: MAA and J-NDA under review
baricitinib (JAK1/JAK2)2
Atopic dermatitis: Phase 3 (BREEZE-AD); approved in EU and Japan
Severe alopecia areata: Phase 3 (BRAVE-AA1, BRAVE-AA2); Submissions in U.S., EU, and Japan
capmatinib (MET)3
NSCLC (with MET exon 14 skipping mutations): Approved as Tabrecta in U.S. and Japan; MAA under review
1 Jakavi (ruxolitinib) licensed to Novartis ex-US.
2 Worldwide rights to baricitinib licensed to Lilly: approved as Olumiant in multiple territories globally for certain patients with moderate-to-severe rheumatoid arthritis; approved as Olumiant in EU and Japan for certain patients with atopic dermatitis.
3 Worldwide rights to capmatinib licensed to Novartis.
2021 Fourth Quarter and Year-End Financial Results
The financial measures presented in this press release for the quarter and year ended December 31, 2021 and 2020 have been prepared by the Company in accordance with U.S. Generally Accepted Accounting Principles ("GAAP"), unless otherwise identified as a Non-GAAP financial measure. Management believes that Non-GAAP information is useful for investors, when considered in conjunction with Incyte’s GAAP disclosures. Management uses such information internally and externally for establishing budgets, operating goals and financial planning purposes. These metrics are also used to manage the Company’s business and monitor performance. The Company adjusts, where appropriate, for expenses in order to reflect the Company’s core operations. The Company believes these adjustments are useful to investors by providing an enhanced understanding of the financial performance of the Company’s core operations. The metrics have been adopted to align the Company with disclosures provided by industry peers.
Non-GAAP information is not prepared under a comprehensive set of accounting rules and should only be used in conjunction with and to supplement Incyte’s operating results as reported under GAAP. Non-GAAP measures may be defined and calculated differently by other companies in our industry.