Risankizumab Meets All Primary Endpoints Reporting Positive Results in Fourth Pivotal Phase 3 Psoriasis Study

- Risankizumab met all co-primary and ranked secondary endpoints in fourth pivotal Phase 3 study; no new safety signals detected across the Phase 3 program for plaque psoriasis1-4*

- In this study, nearly half (47 percent) of risankizumab patients achieved complete skin clearance (PASI 100) versus placebo (1 percent) at week 161

- Among risankizumab patients who achieved clear or almost clear skin (sPGA 0/1) at week 28, 87 percent maintained this response at one year (week 52)1

- Results of this study will support regulatory submissions and were presented at the 8th International Congress of Psoriasis from Gene to Clinic meeting in London

- Risankizumab is an investigational compound designed to selectively inhibit IL-23 by binding to its p19 subunit and is being evaluated for the potential to deliver long-term skin clearance for psoriasis patients with 12-week dosing5

News provided by

AbbVie

Dec 04, 2017, 07:03 ET

NORTH CHICAGO, Ill., Dec. 4, 2017 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global research and development-based biopharmaceutical company, today announced positive top-line results from IMMhance, the fourth pivotal Phase 3 clinical trial evaluating risankizumab (150 mg) for the treatment of patients with moderate to severe plaque psoriasis.¹ There were two phases in this study. Results from the first phase showed that after 16 weeks of treatment, risankizumab met the co-primary endpoints of at least a 90 percent improvement in the Psoriasis and Severity Index (PASI 90) and a static Physician Global Assessment (sPGA) score of clear or almost clear (sPGA 0/1) versus placebo.¹In the second phase of this study, the primary endpoint of sPGA 0/1 at week 52 (one year) was also met.¹ The second phase (week 28 through 104) is evaluating the efficacy and safety of continuous therapy with risankizumab versus randomized withdrawal. Subsequently, retreatment is also being evaluated in this ongoing study. Risankizumab is not approved by regulatory authorities and its safety and efficacy have not been established. Results from IMMhance through week 16 were presented during an oral presentation at the 8^th International Congress of Psoriasis from Gene to Clinic meeting in London on December 2nd.

"These positive results are consistent with the previous data we have seen with risankizumab throughout the pivotal Phase 3 clinical trial program," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "With a significant portion of risankizumab patients achieving high levels of skin clearance, these results add to the data supporting risankizumab's potential to be an impactful new treatment option for patients living with psoriasis. We look forward to sharing additional data from the pivotal trial program with the scientific community and regulatory authorities as we prepare to move forward with global regulatory submissions."

Risankizumab is part of a collaboration with Boehringer Ingelheim, with AbbVie leading future development and commercialization of risankizumab globally. Top-line results of the three other risankizumab Phase 3 psoriasis pivotal trials (ultIMMa-1, ultIMMa-2 and IMMvent) were previously announced in October 2017.^2-4

At week 16, results from the IMMhance study showed that 73 percent of patients receiving risankizumab achieved PASI 90 compared to 2 percent of patients receiving placebo.¹ An sPGA 0/1 was achieved by 84 percent of risankizumab patients compared to 7 percent of placebo patients.¹

Results showed that nearly half (47 percent) of patients receiving risankizumab achieved PASI 100 compared to 1 percent of patients receiving placebo.¹ Additionally, 46 percent of patients receiving risankizumab achieved an sPGA 0 compared to 1 percent of patients receiving placebo.¹ All primary and ranked secondary endpoints achieved p-values of <0.001 versus placebo.¹

IMMhance Efficacy Results at Week 16¹*
	PASI 90**	sPGA 0/1**	PASI 75	PASI 100	sPGA 0
Risankizumab 150 mg (n=407)	73%	84%	89%	47%	46%
Placebo (PBO) (n=100)	2%	7%	8%	1%	1%

*All primary and ranked secondary endpoints achieved p-values of <0.001 versus placebo. Not all secondary endpoints shown.

**The co-primary endpoints of IMMhance were PASI 90 at week 16 and an sPGA score of clear or almost clear (sPGA 0/1) at week 16 compared to placebo.

In the second phase of the study (week 28 through week 104), patients originally randomized to risankizumab who achieved sPGA 0/1 at week 28 were re-randomized to risankizumab (maintenance) or placebo (withdrawal).¹ Beginning at week 32, any patient who experienced a relapse (defined as an sPGA score of moderate to severe [>3]) was retreated with risankizumab immediately, four weeks later and every 12 weeks thereafter.¹

The primary endpoint of the second phase of the study (week 28 through week 104) was sPGA 0/1 at one year (week 52).¹ Among the maintenance group, 87 percent of patients maintained sPGA 0/1 at one year compared to 61 percent of patients in the withdrawal group (p-value of <0.001).¹

"The significant rates of skin clearance achieved at week 16 are very encouraging for patients with moderate to severe plaque psoriasis," said Andrew Blauvelt, M.D., M.B.A., dermatologist and president of Oregon Medical Research Center and the lead investigator for the study. "These data also indicate that continuous treatment with risankizumab has the potential to deliver better disease improvement for patients over time when compared to withdrawing them from therapy after an initial response."

IMMhance Efficacy Results at One Year (Week 52)¹***

Maintenance Group

(re-randomized to risankizumab 150 mg)

(n=111)

Withdrawal Group

(re-randomized to PBO)

(n=225)

sPGA 0/1

87%

61%

***The primary endpoint of IMMhance from week 28 through week 104 was sPGA clear or almost clear (sPGA 0/1) at one year (p-value of <0.001).

The safety profile in IMMhance was consistent with previously reported Phase 3 clinical trials, with no new safety signals detected across the Phase 3 program.^1-4In this study, serious adverse events occurred in 2 percent of patients in the risankizumab group and 8 percent of patients in the placebo group through week 16.¹ In the second part of the study until the data was locked, serious adverse events occurred in 6 percent of patients re-randomized to the risankizumab group and 6 percent of patients re-randomized to the placebo group.¹ In the second phase of the study, one patient receiving risankizumab had intestinal adenocarcinoma and metastatic hepatic cancer and died on study day 339.¹ A second patient treated with risankizumab died on study day 263 due to an unknown cause that was adjudicated as a major adverse cardiovascular event (MACE).¹ There were two additional adjudicated MACE cases at the time of database lock.¹ One event occurred in the placebo arm in the first phase of the study and the other occurred in the risankizumab arm in the second phase.¹ All three patients had a past history of cardiovascular risk factors.¹

AbbVie is continuing to evaluate the potential of risankizumab across several immune-mediated conditions.^6,7

About the Phase 3 IMMhance study¹The IMMhance study is an ongoing Phase 3, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of risankizumab compared to placebo in adult patients with moderate to severe plaque psoriasis. In the first phase, patients were randomized 4:1 to risankizumab (150 mg), given as a subcutaneous injection at baseline, 4 weeks later and every 12 weeks thereafter, or placebo. The co-primary endpoints were achievement of at least a 90 percent improvement in the PASI score (PASI 90) and achievement of an sPGA 0/1 at week 16 compared to placebo. Patients who were originally randomized to placebo switched to risankizumab at week 16.

In the second phase of this study (week 28 through week 104), patients originally randomized to risankizumab who achieved sPGA 0/1 at week 28 were re-randomized to risankizumab (maintenance) or placebo (withdrawal). Beginning at week 32, any patient who experienced a relapse (defined as an sPGA moderate to severe [>3]) was retreated with risankizumab immediately, four weeks later and every 12 weeks thereafter. The primary endpoint from week 28 through week 104 of the study was sPGA 0/1 at one year. This Phase 3 study has been conducted in cooperation between AbbVie and Boehringer Ingelheim. The trial is ongoing and will evaluate patients up to 104 weeks. More information on this trial can be found at www.clinicaltrials.gov (NCT02672852).

Overview of the Risankizumab Phase 3 Psoriasis Program^1-4The global risankizumab Phase 3 psoriasis program evaluates more than 2,000 patients with moderate to severe plaque psoriasis in four pivotal studies. The studies include assessments of efficacy, safety and tolerability of risankizumab. Key measures of efficacy include measures of disease activity and skin clearance, including PASI 90, PASI 100 and sPGA 0/1, as well as long-term clinical outcomes. More information on this program can be found at www.clinicaltrials.gov (NCT02672852, NCT02694523, NCT02684370, NCT02684357). An overview of results from the risankizumab Phase 3 psoriasis program is below.

Co-Primary Endpoint Results at Week 16 Across the Risankizumab Phase 3 Psoriasis Program^1-4
Study	PASI 90			sPGA (0/1)
Study	PBO^†	Risankizumab^†	Ustekinumab^‡	PBO^†	Risankizumab^†	Ustekinumab^‡
ultIMMa-1 (PBO n=102, risankizumab n=304, ustekinumab n=100)	5%	75%	42%	8%	88%	63%
ultIMMa-2 (PBO n=98, risankizumab n=294, ustekinumab n=99)	2%	75%	48%	5%	84%	62%
IMMhance (PBO n=100, risankizumab n=407)	2%	73%	N/A	7%	84%	N/A
	Adalimumab^†	Risankizumab^†		Adalimumab^†	Risankizumab^†
IMMvent (adalimumab n=304, risankizumab n=301)	47%	72%	N/A	60%	84%	N/A

^†Co-primary endpoints.

^‡Ranked secondary endpoint compared to risankizumab.

Week 16 (Part A) Incidence of Patients with Adverse Events Across the Risankizumab Phase 3 Psoriasis Program^1-4

ultIMMa-1

ultIMMa-2

IMMvent

IMMhance

RIS^§

(n=304)

n (%)

UST^‖

(n=100)

n (%)

PBO
(n=102)

n (%)

RIS

(n=294)

n (%)

UST

(n=99)

n (%)

PBO
(n=98)

n (%)

RIS

(n=301)

n (%)

ADA^Δ

(n=304)

n (%)

RIS

(n=407)

n (%)

PBO
(n=100)

n (%)

Any Adverse Event

151

(49.7)

(50.0)

(51.0)

134

(45.6)

(53.5)

(45.9)

168

(55.8)

173

(56.9)

185

(45.5)

(48.0)

Serious Adverse Events

(2.3)

(8.0)

(2.9)

(2.0)

(3.0)

(1.0)

(3.3)

(3.0)

(2.0)

(8.0)

Any Adjudicated MACE

(0.3)

(1.0)

Any Serious Infection

(0.3)

(3.0)

(1.0)

(0.3)

(1.0)

Any Malignant Tumor

(0.3)

(1.0)

(0.3)

(0.7)

Deaths

(0.3)

(0.7)

^§RIS=risankizumab

^‖UST=ustekinumab

^ΔADA=adalimumab

Longer term safety, through 1.5 years in the first patients who enrolled, was evaluated for patients initially randomized to risankizumab (150 mg) or those who switched from placebo to risankizumab (n=1,590) and those patients randomized to ustekinumab (n=199). Overall rates of adverse events per 100 patient-years (PY) were 245.6 with risankizumab compared to 281.0 with ustekinumab through week 52.¹ Serious adverse events were 9.8/100PY (risankizumab) compared with 10.9/100PY (ustekinumab); serious infections were 1.6/100PY (risankizumab) compared with 2.5/100PY (ustekinumab); MACE were 0.5/100PY (risankizumab) compared with 0.0/100PY (ustekinumab); any malignancy was 1.5/100PY (risankizumab) compared with 0.5/100PY (ustekinumab); deaths were 0.3/100PY (risankizumab) compared with 0.0/100PY (ustekinumab).¹

About the Phase 3 ultIMMa-1 and ultIMMa-2 studies^2-3ultIMMa-1 and ultIMMa-2 are replicate Phase 3, randomized, double-blind, double-dummy, placebo- and active-controlled studies designed to evaluate the safety and efficacy of risankizumab compared to placebo or ustekinumab in adult patients with moderate to severe plaque psoriasis. The active comparator used for these studies was sourced from the European Union.

About the Phase 3 IMMvent study⁴The IMMvent study is a Phase 3 randomized, double-blind, double-dummy, active-controlled study designed to evaluate the safety and efficacy of risankizumab compared to adalimumab in adult patients with moderate to severe plaque psoriasis.

About Risankizumab
Risankizumab is an investigational compound that is designed to selectively block IL-23 by binding to its p19 subunit.⁵ IL-23, a key cytokine involved in inflammatory processes, is thought to be linked to a number of immune-mediated diseases.⁸ Phase 3 trials of risankizumab in psoriasis are ongoing, and it is also being investigated to treat Crohn's disease and psoriatic arthritis.^6,7 Future trials are planned to investigate risankizumab in ulcerative colitis.

Risankizumab is not approved by regulatory authorities. Safety and efficacy have not been established.

About HUMIRA (adalimumab) in the European Union⁹HUMIRA is indicated for the treatment of moderate to severe chronic plaque psoriasis in adult patients who are candidates for systemic therapy.

Important EU Safety Information⁹
HUMIRA is contraindicated in patients with active tuberculosis or other severe infections such as sepsis, and opportunistic infections and in patients with moderate to severe heart failure (NYHA class III/IV). It is also contraindicated in patients hypersensitive to the active substance or to any of the excipients. The use of HUMIRA increases the risk of developing serious infections which may, in rare cases, be life-threatening. Rare cases of lymphoma and leukemia have been reported in patients treated with HUMIRA. On rare occasions, a severe type of cancer called hepatosplenic T-cell lymphoma has been observed and often results in death. A risk for the development of malignancies in patients treated with TNF-antagonists cannot be excluded. The most frequently reported adverse events across all indications included respiratory infections, injection site reactions, headache and musculoskeletal pain.

Globally, prescribing information varies; refer to the individual country product label for complete information.

(See SmPC for full safety details)

About AbbVie
AbbVie is a global, research and development-based biopharmaceutical company committed to developing innovative advanced therapies for some of the world's most complex and critical conditions. The company's mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook or LinkedIn.

Forward-Looking Statements
Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry.

Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2016 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

REFERENCES

¹AbbVie. Data on File, ABVRRTI65374.
²AbbVie. Data on File, RRTI65191.
³AbbVie. Data on File, RRTI65192.
⁴AbbVie. Data on File, RRTI65055.
⁵Papp K.A., et al. Risankizumab versus Ustekinumab for Moderate-to-Severe Plaque Psoriasis. NEJM. 2017.
⁶A Study of the Efficacy and Safety of Risankizumab in Subjects With Moderately to Severely Active Crohn's Disease. Clinicaltrials.gov. 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT03105128?cond=RISANKIZUMAB&draw=3&rank=15. Accessed December 1, 2017.
⁷BI 655066/ABBV-066/Risankizumab Compared to Placebo in Patients With Active Psoriatic Arthritis. Clinicaltrials.gov. 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT02719171?cond=RISANKIZUMAB&draw=3&rank=17. Accessed December 1, 2017.
⁸Duvallet E, Sererano L, Assier E, et. al. Interleukin-23: a key cytokine in inflammatory diseases. Ann Med. 2011 Nov;43(7):503-11.
⁹HUMIRA [Summary of Product Characteristics]. AbbVie Ltd.; Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000481/WC500050870.pdf. Last updated March 31, 2017. Accessed December 1, 2017.