8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of

the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported) October 24, 2008

INSPIRE PHARMACEUTICALS, INC.

(Exact Name of Registrant as Specified in its charter)

Delaware	000-31135	04-3209022
(State or Other Jurisdiction of Incorporation)	(Commission File Number)	(IRS Employer Identification No.)

4222 Emperor Boulevard, Suite 200, Durham, North Carolina	27703-8466
(Address of Principal Executive Offices)	(Zip Code)

Registrant’s telephone number, including area code (919) 941-9777

(Former Name or Former Address, if Changed Since Last Report.)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

¨ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

¨ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

¨ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

¨ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Item 7.01 Regulation FD Disclosure.

On October 24, 2008, Inspire Pharmaceuticals, Inc. (NASDAQ: ISPH) issued a press release furnished as Exhibit 99.1 to this report, announcing new data relating to its denufosol phase 3 program.

On October 25, 2008, a presentation of Inspire Pharmaceutical, Inc.’s TIGER-1 data will take place at a symposium session entitled “New Therapies for CF Lung Disease: Update on Clinical Trials” at the annual North American Cystic Fibrosis Conference in Orlando, Florida. The slides to be presented are furnished as Exhibit 99.2 to this report and are incorporated herein by reference.

The furnishing of the attached information is not an admission as to the materiality of any information set forth therein.

The information in this Form 8-K and the exhibits attached hereto shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934 (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall they be deemed incorporated by reference in any filing under the Securities Act of 1933 or the Exchange Act, except as expressly set forth by specific reference in such a filing.

Item 9.01 Financial Statements and Exhibits

(d) Exhibits

No.	Description
99.1	Press release dated October 24, 2008
99.2	slides re: A Phase 3 Study of Denufosol for Cystic Fibrosis: TIGER-1 Results

- 2 -

SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the Registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

Inspire Pharmaceuticals, Inc.
By:	/s/ Joseph M. Spagnardi
	Joseph M. Spagnardi,
	Senior Vice President, General Counsel and Secretary

Dated: October 24, 2008

- 3 -

EXHIBIT INDEX

No.	Description
99.1	Press release dated October 24, 2008
99.2	slides re: A Phase 3 Study of Denufosol for Cystic Fibrosis: TIGER-1 Results

- 4 -

EX-99.1

Exhibit 99.1

For Immediate Release

Investor Contact:	Media Contact:
Inspire Pharmaceuticals, Inc.	BMC Communications
Jenny Kobin	Dan Budwick
VP, Investor Relations and Corporate Communications	(973) 271-6085
(919) 941-9777, Extension 219

INSPIRE ANNOUNCES NEW DATA FROM DENUFOSOL PHASE 3 PROGRAM AT

NORTH AMERICAN CYSTIC FIBROSIS CONFERENCE

-TIGER-1 Open-Label Extension Completed-

-Open-Label Extension Suggests Progressive Improvement in FEV₁-

DURHAM, NC—October 24, 2008—Inspire Pharmaceuticals, Inc. (NASDAQ: ISPH) announced today the presentation of additional data from TIGER-1, the Company’s first Phase 3 trial with denufosol tetrasodium for the treatment of cystic fibrosis, at the 22^nd Annual North American Cystic Fibrosis Conference (NACFC) in Orlando, FL on October 23 - 25, 2008.

As previously announced, the TIGER-1 trial demonstrated statistical significance for its primary efficacy endpoint, which was the change in FEV₁ (Forced Expiratory Volume in One Second) from baseline at the trial endpoint (at 24 weeks or last observation carried forward). The new data presented today at the NACFC indicate that patients who continued to receive denufosol for an additional 24 weeks during the open-label extension experienced a progressive improvement in FEV₁. These patients who received denufosol for 48 weeks during TIGER-1 experienced a mean change from baseline in FEV₁ of 115 ml, almost a two-and-a-half fold increase compared to the initial 48 ml increase at the end of the 24-week placebo-controlled portion of the trial.

The patients who crossed over from placebo to denufosol at Week 24 also experienced improvements in FEV₁ when receiving denufosol during the open-label extension. These patients had a 78 ml increase from baseline, of which only 3 ml were observed during the 24-week placebo-controlled portion of the trial.

The patient retention rate in the open-label extension was high, with an approximate 95% completion rate for the patients who entered the open-label extension. The detailed results from the open-label extension of TIGER-1 are expected to be available in the first quarter of 2009.

The Company also announced an enrollment update for TIGER-2, Inspire’s second Phase 3 clinical trial with denufosol. As of October 17, 2008, 133 patients had been randomized at 41 of approximately 100 clinical sites across the United States, Canada, Australia and New Zealand.

4222 Emperor Boulevard, Suite 200 — Durham, North Carolina 27703

Telephone 919.941.9777 — Fax 919.941.9797

Frank J. Accurso, M.D., Professor of Pediatrics and Cystic Fibrosis Center Director, The Children’s Hospital, University of Colorado Denver and lead principal investigator of TIGER-1, stated, “These are very exciting, promising data suggesting that denufosol can make a difference for CF patients, particularly since the therapy could benefit all types of patients regardless of their specific genetic mutation. The clinically-meaningful improvement in FEV₁ that continues over time without apparent abatement at Week 48 is particularly notable in patients with relatively mild lung function impairment.”

“We greatly appreciate the dedication of the clinical investigators and study coordinators that have participated in our Phase 3 clinical program. We would also like to thank the patients and their families who participated in TIGER-1 and those who have elected to participate in the ongoing 48-week TIGER-2 trial,” stated Christy L. Shaffer, Ph.D., President and CEO of Inspire. “We are pleased to have the opportunity to announce this new data at the North American CF Conference, since we have worked closely with the CF Foundation throughout the development of denufosol and appreciate the valuable support and advice they have provided.”

NACFC Denufosol Presentation Details

Key highlights of the denufosol development program are included in the Plenary Session II presented by Preston W. Campbell, III, M.D., Executive Vice President for Medical Affairs at the Cystic Fibrosis Foundation (CFF):

• The CFF Pipeline: The Amazing Story of Progress, Hope, and Challenge

• Friday, October 24, 2008; 9:00 a.m. - 10:30 a.m.

• Location: Sabal/Royal/Canary

An oral presentation of the TIGER-1 data will take place during the Symposium Session entitled, “New Therapies for CF Lung Disease: Update on Clinical Trials.” The denufosol portion will be presented by Frank J. Accurso, M.D., Professor of Pediatrics and Cystic Fibrosis Center Director, The Children’s Hospital, University of Colorado Denver and lead principal investigator of TIGER-1:

• The TIGER-1 Phase 3 Clinical Trial of Denufosol in Cystic Fibrosis

• Saturday, October 25, 2008; 11:50 a.m. - 12:20 p.m.

• Location: Palms/Sabal

A poster related to preclinical pharmacokinetic denufosol data is also available:

• Pharmacokinetics of Denufosol: Results from Preclinical Studies (C. Crean; S.J. Godin; M. Cowlen; D. Kellerman)

• Thursday, October 23, 2008; 11:50 a.m. - 1:50 p.m.

• Friday, October 24, 2008; 4:30 p.m. - 6:30 p.m.

• Location: Cypress 1-2 (both days)

Inspire is hosting an investor and analyst meeting in conjunction with NACFC regarding the denufosol Phase 3 clinical program. Related materials from the NACFC will be posted on Inspire’s website, www.inspirepharm.com, following the conference.

4222 Emperor Boulevard, Suite 200 — Durham, North Carolina 27703

Telephone 919.941.9777 — Fax 919.941.9797

Page 2

About the Denufosol Phase 3 Development Program

The TIGER-1 Phase 3 clinical trial was a 24-week, double-blind, placebo-controlled, randomized clinical trial comparing 60 mg of denufosol to placebo, administered three-times daily by jet nebulizer, in 352 CF patients with FEV₁ ³ 75%. This portion was followed by a 24-week open-label denufosol extension in approximately 300 patients. In June 2008, Inspire announced the trial demonstrated statistical significance for its primary efficacy endpoint, which was the change in FEV₁ (Forced Expiratory Volume in One Second) from baseline at the trial endpoint (at 24 weeks or last observation carried forward). Patients treated with denufosol had a statistically significant improvement in FEV₁ compared to placebo (45 milliliter treatment group difference, p = 0.047). On average, patients on denufosol improved in FEV₁ relative to baseline whereas patients on placebo remained essentially unchanged. Secondary endpoints were also evaluated during the placebo-controlled portion of TIGER-1. There was a trend in differences in FEF_25%-75% (Forced Expiratory Flow 25%-75%), a measure of small airway function, favoring denufosol over placebo (87.5 milliliters/second treatment group difference, p = 0.072). There were no statistically significant differences between denufosol and placebo relative to the frequency of pulmonary exacerbations.

The TIGER-2 Phase 3 clinical trial is a 48-week, double-blind, placebo-controlled, randomized clinical trial comparing 60 mg of denufosol to placebo, administered three-times daily by jet nebulizer, in approximately 450 patients with FEV₁ ³ 75% and £ 110% predicted normal. The primary efficacy endpoint is change from baseline in FEV₁ (in liters) at the 48-week trial endpoint. Inspire is targeting completion of TIGER-2 enrollment in 2009.

About Denufosol

Denufosol is designed to enhance the lung’s innate mucosal hydration and mucociliary clearance mechanisms, which in CF patients are impaired due to a genetic defect. By hydrating airways and stimulating mucociliary clearance through activation of the P2Y₂ receptor, denufosol can potentially help keep the lungs of CF patients clear of thickened mucus, reduce infections and limit the damage that occurs as a consequence of the prolonged retention of thick and tacky infected secretions. Denufosol for the treatment of CF has been granted Fast Track designation and orphan drug status in the United States by the FDA and orphan drug designation in Europe by the European Medicines Agency (EMEA). Inspire holds world-wide rights for denufosol.

About Inspire

Inspire is a biopharmaceutical company dedicated to discovering, developing and commercializing prescription pharmaceutical products for ophthalmic and pulmonary diseases. Inspire is currently developing products for dry eye, cystic fibrosis and glaucoma. Inspire employs a U.S. sales force for the promotion of AzaSite^® (azithromycin ophthalmic solution) 1% for bacterial conjunctivitis, Elestat^® (epinastine HCl ophthalmic solution) 0.05% for allergic conjunctivitis and Restasis^® (cyclosporine ophthalmic emulsion) 0.05% for dry eye. Elestat and Restasis are registered trademarks owned by Allergan, Inc. AzaSite is a registered trademark owned by InSite Vision Incorporated. For more information, visit www.inspirepharm.com.

4222 Emperor Boulevard, Suite 200 — Durham, North Carolina 27703

Telephone 919.941.9777 — Fax 919.941.9797

Page 3

Forward-Looking Statements

The forward-looking statements in this news release relating to management’s expectations and beliefs are based on preliminary information and management assumptions. Specifically, no assurance can be made with respect to the ability of denufosol tetrasodium to show improvement in FEV₁ in a placebo-controlled trial longer than 24 weeks, including without limitation progressive improvement over the course of a clinical trial; the timing of the detailed results from the open-label extension of TIGER-1; the ability of denufosol to make a difference for CF patients, including without limitation the ability of denufosol to benefit all types of patients regardless of their specific genetic mutation; the ability of denufosol to show a clinically meaningful improvement in FEV₁ that continues over time without apparent abatement at Week 48 (or any other time period); or the timing of completion of TIGER-2 enrollment. Such forward-looking statements are subject to a wide range of risks and uncertainties that could cause results to differ in material respects, including those relating to product development, revenue, expense and earnings expectations, intellectual property rights, adverse litigation developments, competitive products, results and timing of clinical trials, success of marketing efforts, the need for additional research and testing, delays in manufacturing, funding, and the timing and content of decisions made by regulatory authorities, including the U.S. Food and Drug Administration. Further information regarding factors that could affect Inspire’s results is included in Inspire’s filings with the SEC. Inspire undertakes no obligation to publicly release the results of any revisions to these forward-looking statements that may be made to reflect events or circumstances after the date hereof.

# # #

4222 Emperor Boulevard, Suite 200 — Durham, North Carolina 27703

Telephone 919.941.9777 — Fax 919.941.9797

Page 4

EX-99.2

A Phase 3 Study of Denufosol for

A Phase 3 Study of Denufosol for

Cystic Fibrosis:

Cystic Fibrosis:

TIGER-1 Results

TIGER-1 Results

Lead PI TIGER-1

Lead PI TIGER-1

1

Frank Accurso, MD

Frank Accurso, MD

Professor of Pediatrics

Professor of Pediatrics

Cystic Fibrosis Center Director

Cystic Fibrosis Center Director

The Children’s Hospital

The Children’s Hospital

University of Colorado Denver

University of Colorado Denver

Transport of

Transport of

Generate

Generate

Ions to

Ions to

Epithelial

Epithelial

Rehydration

Rehydration

Exhibit 99.2

2

Cystic Fibrosis Therapies

Significant need for agent that addresses basic defect of ion transport prior to onset

of infection and inflammation:

Antibiotic

Mucus

Regulation

Anti-

Inflammatory

Gene

Therapy,

Potentiator

/Corrector

Lung

structural

damage

CFTR defect

Thickened

airway

secretions

Bacterial

colonization

Irreversible

inflammation

Lung Transplant

Inefficient

ion transport

Inefficient

ion transport

Ion

Transport

Restoration

denufosol

P2Y

2

Receptor Activation

Inhaled P2Y

2

receptor agonists increase mucosal hydration and the natural mechanism

of mucociliary clearance in the lung

sodium absorption

chloride ion and fluid secretion

cilia beat frequency

mucin

secretion from goblet cells

surfactant release from type II alveolar cells

3

TIGER-1 Clinical Study Design

CF patients

5 years with FEV

1

75% predicted

Standard of care allowed

352 CF patients randomized at 62 treatment centers

denufosol 60 mg

TID (n=314)

period

treatment period

24-week safety

extension period

1-week post-treatment

follow-up

placebo TID (n=174)

Placebo-controlled 24-week

Screening

denufosol 60 mg TID (n=178)

4

Demographic and Background

Characteristics (Intent to Treat Population: ITT*)

89%

95%

Pancreatic enzymes

82%

79%

Bronchodilators

39%

40%

Chronic macrolides

37%

38%

Chronic inhaled antibiotics

77%

77%

Dornase

alfa

42%

48%

PA

+ status

81%

84%

FEF

25%-75%

% Predicted

93%

92%

FEV

1

% Predicted

54%

49%

% Males

38 (21%)

33 (19%)

19 n (%)

59 (33%)

64 (37%)

12-18, n (%)

81 (46%)

77 (44%)

5-11, n (%)

14.3

14.9

Mean age, yrs

Denufosol (n=178)

Placebo (n=174)

*ITT=All patients randomized

5

Disposition by Treatment Group

5 (3%)

2 (1%)

Discontinued from placebo-controlled

phase due to an AE, n (%)

19 (11%)

18 (10%)

Discontinued early: placebo-controlled

phase, n (%)

159 (89%)

156 (90%)

Completed through Week 24, n (%)

178 (100%)

174 (100%)

Intent-to-treat population, n (%)

178

174

Randomized, n

Denufosol

Placebo

6

Primary Efficacy Results –

Placebo–Controlled (ITT)

0

10

20

30

40

50

60

70

Placebo

Denufosol

Met primary efficacy

endpoint: change in

FEV

1

from baseline to

endpoint*

45 mL treatment effect

(p = 0.047)

“Real world”

design

Broader population

Patients on multiple

therapies that improve

FEV

1

3

48

*Endpoint is the Week 24 value or the last observation carried

forward for patients who withdrew early.

7

-40

-20

0

20

40

60

80

100

120

140

Mean Change from Baseline FEV

1

CFB=Change from Baseline

ITT Population

Placebo

Denufosol

Treatment Week

0

4

12

24

28

36

48

8

-40

-20

0

20

40

60

80

100

120

140

Mean Change from Baseline FEV

1

CFB=Change from Baseline

ITT Population

Placebo

Denufosol

Treatment Week

0

4

12

24

28

36

48

9

-40

-20

0

20

40

60

80

100

120

140

0

4

12

24

28

36

48

Mean Change from Baseline FEV

1

CFB=Change from Baseline

ITT Population

Treatment Week

Placebo

Denufosol

Placebo Switched to

Denufosol

denufosol-only, open-label phase

10

Placebo

Denufosol

Mean Change from Baseline FEF

25%-75%

-100

-80

-60

-40

-20

0

20

40

60

80

100

120

140

160

0

4

12

24

28

36

48

CFB=Change from Baseline

ITT Population

Treatment Week

11

Placebo

Denufosol

Mean Change from Baseline FEF

25%-75%

-100

-80

-60

-40

-20

0

20

40

60

80

100

120

140

160

0

4

12

24

28

36

48

CFB=Change from Baseline

ITT Population

Treatment Week

12

Placebo

Denufosol

Placebo Switched to

Denufosol

Mean Change from Baseline FEF

25%-75%

-100

-80

-60

-40

-20

0

20

40

60

80

100

120

140

160

0

4

12

24

28

36

48

denufosol-only, open-label phase

CFB=Change from Baseline

ITT Population

Treatment Week

13

0

20

40

60

80

100

120

140

160

180

Effect of Denufosol in ITT Population and

Patients

110% Predicted

56

45

ITT

p-value = 0.047

(n=352)

0

20

40

60

80

100

120

140

160

180

110% Predicted

p-value = 0.015

(n=329)

112

88

ITT

p-value = 0.072

(n=352)

110% Predicted

p-value = 0.025

(n=329)

FEV

1

FEF

25%-75%

14

Secondary Efficacy Endpoint:

Pulmonary Exacerbation

Incidence as expected in this patient

population (i.e. low)

No significant difference between groups

May be confounded by denufosol’s

pharmacology

Longer treatment time may be needed

15

Pulmonary

Exacerbations

(Fuchs’

Criteria)

During Placebo–Controlled Phase

0

20

40

60

80

100

0

4

8

12

16

20

24

28

Placebo

Denufosol 60 mg

Log rank statistic = 2.379

p-value = 0.123

Time (Weeks)

ITT Population

16

Hospitalizations/Missed School and Work

During Placebo–Controlled Phase

3.6 (7.7)

13 (7.3%)

Denufosol

(n=178)

0.610

3.4 (7.9)

Mean Days of

CF-Related

Missed School or

Work (SD)

0.843

14 (8.0%)

Hospitalizations/

ER visits for

respiratory

complaint, n (%)

P-value

Placebo

(n=174)

ITT Population

17

Cystic Fibrosis Questionnaire –

Respiratory Subscale

-3.08 (15.43)

-1.48 (16.74)

CFB Week 24

81.4 (14.56)

(n=173)

Mean (SD)

Denufosol

79.3 (15.98)

Baseline

(n=162)

Mean (SD)

CFQ -

Respiratory

Placebo

ITT Population

18

High Level of Compliance with TID Dosing

Compliance during the placebo-controlled phase

~90% of patients were compliant

-

Comparable between denufosol and placebo

Average number of daily doses = 2.7

Excellent patient retention throughout study

352 patients were randomized

~90% completed the 24-week placebo-controlled phase

~99% of those who completed the placebo-controlled

phase elected to continue into the open-label extension

19

Most Common AEs (

10% in any group)

20 (11%)*

43 (25%)

Headache

36 (20%)

27 (15%)

Pyrexia

61 (34%)

51 (29%)

Pulmonary exacerbation

15 (8%)

23 (13%)

Pseudomonas infection

17 (10%)*

31 (18%)

Sinusitis

29 (16%)

30 (17%)

Productive cough

18 (10%)*

31 (18%)

Rhinorrhea

34 (19%)

32 (18%)

Pharyngolaryngeal pain

26 (15%)

34 (19%)

Nasal congestion

96 (54%)

103 (59%)

Cough

165 (93%)

169 (97%)

Any AE, n (%)

Denufosol (n=177)

Placebo (n=175)

*p-value <0.05 vs placebo

Safety Population

20

No Difference in Growth Between Groups

45.3

44.5

Baseline

0.922

1.01

1.03

CFB at 6 months

19.8

0.03

147.5

1.90

Denufosol

(n=177)

0.769

19.3

0.07

BMI, kg/m

Baseline

CFB at 6 months

Weight, kg

0.871

148.1

1.83

Height, cm

Baseline

CFB at 6 months

P-value

Placebo

(n=175)

Mean Change from Baseline (CFB)

Safety Population

2

21

Safety Overview

Safety

and

tolerability

profile

-

favorable

Relatively few SAEs and withdrawals due to AEs

AE profile

Comparable between treatment groups

SAEs comparable between treatment groups

Placebo: 14 (8%)

Denufosol: 16 (9%)

No evidence of systemic adverse effects (labs, vital

signs)

Minimal to no systemic absorption following dosing

No significant effect on growth (height/weight/BMI)

22

TIGER-1 Summary

Large multicenter, randomized, double-blind,

placebo-controlled trial

Used with other therapies

No significant interactions with concomitant medications

Significant

improvement

in

FEV

1

Comparable exacerbation rates

Well-tolerated

Good adherence to TID regimen

23

0

10

20

30

40

50

60

70

Placebo

Denufosol

Primary Efficacy Results –

Placebo–Controlled (ITT)

Endpoint is the Week 24 value or the last observation carried forward

for patients who withdrew early.

24

-150

-100

-50

0

50

100

= 41 mL

p-value = 0.101

Subgroup:

FEV

in

Patients

Who

Did

NOT

Experience an Exacerbation (Fuchs’

Criteria)

n=141 (81%)

n=131 (74%)

Placebo

Denufosol

1

25

-150

-100

-50

0

50

100

Subgroup: FEV

in Patients Who Did Experience

an Exacerbation (Fuchs’

Criteria)

n=33 (19%)

n=47 (26%)

= 101 mL

p-value = 0.062

Placebo

Denufosol

1

26

Projected Long-term Impact of Slowing the

Rate of Decline

Konstan., Pediatr

Pulmonol., 2008. 43, S24-28

27

TIGER-2 Study Design

Current Status

~100 sites in North America, Australia and New Zealand

As of October 17, 133 patients randomized at 41 sites

TIGER-2 Study Design

Primary

outcome:

FEV

1

48 weeks; placebo-controlled

Planned sample size n=~450

Open-label extension to follow

28

Acknowledgements

Cystic Fibrosis Foundation

CFFT Therapeutics Development Network

CFFT Data Monitoring Committee

TIGER-1 Principal Investigators and 

Research Coordinators