Denufosol TIGER II - Fail

RALEIGH, N.C. (AP) — Inspire Pharmaceuticals Inc. said Monday that its potential cystic fibrosis drug failed to meet key treatment goals in a late-stage study. Its shares tumbled more than 54 percent in pre-market trading.

The company is studying denufosol tetrasodium as a treatment for the genetic condition, which results in thick mucus buildup in the lungs. The results from the latest Tiger-2 test mark a reversal from the prior successful Tiger-1 study of the drug candidate.

"These Tiger-2 results were disappointing and unexpected given the treatment effect observed in the Tiger-1 trial," President and CEO Adrian Adams said in a statement. "We will conduct a thorough analysis of the data to fully understand the results from this trial and the impact on any future development of denufosol and on the company going forward."

The latest study involved 466 patients taking either denufosol or placebo.

Adams said the company will continue to focus on its drug candidates aimed at treating glaucoma.
Shares of Inspire fell $4.58, or 54.5 percent, to $3.82 in pre-market trading on Monday. The stock closed at $8.40 on Friday.

http://www.bloomberg.com/news/2011-01-03/inspire-cystic-fibrosis-drug-fails-in-study.html

Denufosol Offers Hope for Early Intervention in Cystic Fibrosis Patients

Novel Drug Offers Hope for Early Intervention in Cystic Fibrosis Patients

ScienceDaily (Dec. 17, 2010) — Cystic fibrosis (CF) patients with normal to mildly impaired lung function may benefit from a new investigational drug designed to help prevent formation of the sticky mucus that is a hallmark of the disease, according to researchers involved in a phase 3 clinical trial of the drug. Called denufosol, the investigational medication can be given early in the CF disease process, and may help delay the progression of lung disease in these patients, the researchers found.


The findings were published online ahead of the print edition of the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.




"Although the lungs of children with CF are thought to be normal at birth, studies have demonstrated significant lung damage that occurs early in life in children suffering from cystic fibrosis," said lead investigator Frank Accurso, MD, professor of pediatrics, University of Colorado School of Medicine, Denver. "Many patients continue to suffer progressive loss of lung function despite treatment of complications. Because denufosol can be used early in life, it offers hope for delaying or preventing the progressive changes that lead to irreversible airflow obstruction in CF patients."



Denufosol belongs to a class of drugs known as ion channel regulators. These drugs help balance the flow of ions through cell membranes, helping normalize the airway surface hydration and mucus clearance impairment present in patients who suffer from the disease. In cystic fibrosis, the ion sodium chloride does not flow normally through cell membranes, resulting in thick, sticky mucus which is difficult to cough out of the airways. In addition to causing breathing problems, the mucus becomes a breeding ground for bacteria and can cause serious respiratory infections.



Denufosol works by increasing chloride secretion, inhibiting sodium absorption and increasing the beat frequency of the tiny hairs, or "cilia," lining the airways move to clear mucus. Combined, these effects enhance airway hydration and aid in clearing mucus. The drug is different from other CF medications, which primarily treat the symptoms rather than the underlying causes, said Dr. Accurso, who is also the director of University of Colorado's cystic fibrosis center.



This study is the first large, phase 3 trial of an ion channel regulator in cystic fibrosis patients with little or no baseline pulmonary function impairment.



"Abnormal ion transport and defective mucociliary clearance are fundamental defects that contribute to complications of CF lung disease, including mucus plugging, chronic bacterial infection, inflammation and progressive airway damage," Dr. Accurso noted. "Although currently available drugs target these complications, denufosol was designed to treat the underlying defects that cause the complications, and could potentially modify the course of the disease, particularly when administered early in the disease process."



Researchers enrolled 352 cystic fibrosis patients 5 years of age or older, and enrolled them to receive either inhaled denufosol or placebo three times daily for 24 weeks, followed by a 24-week open-label period when all patients received denufosol. At baseline, most patients enrolled had mild impairment of lung function and were taking multiple medications to control their symptoms. Because the study outcomes were measured using spirometry, a lung function test that can be difficult to accurately use in young children, patients under five years of age were excluded.



Patients' exhalation rates and lung volume were measured throughout the study, and also were monitored for adverse events, such as cough, congestion, fever or sinusitis. At the end of the 24-week period, researchers determined patients who received denufosol had better lung exhalation rates than those in the placebo group, whose exhalation volumes remained relatively unchanged from the start of the study. Both groups had similar numbers and types of adverse events, with the denufosol patients experiencing significantly fewer headaches and lower rates of sinusitis and runny nose.



Although children under five years of age were excluded from this study, Dr. Accurso said future studies likely would address the use of denufosol in this younger population.



"Considering the evidence that early inflammation and infection results in impaired lung function and structural damage in early childhood, future studies of the effects of denufosol during the first 5 years of life is warranted," he said.



A second, similar phase 3 trial incorporating a longer placebo-controlled treatment phase is ongoing to further investigate the effectiveness of denufosol in patients with CF, Dr. Accurso added.

 
http://www.sciencedaily.com/releases/2010/12/101217145643.htm

New Data Presented At ECFS Conference Highlight Potential for Denufosol to Provide Benefit to CF Patients

Jun. 17, 2010 (Business Wire) -- Inspire Pharmaceuticals, Inc. (NASDAQ: ISPH) announced today that data is being presented on denufosol tetrasodium, an investigational therapy for cystic fibrosis (CF), during an oral presentation and poster presentations at the 33^rd Annual European Cystic Fibrosis Society (ECFS) Conference June 16 - 19, 2010 in Valencia, Spain. The data from Inspire’s first Phase 3 clinical trial with denufosol, TIGER-1, suggest that denufosol, an inhaled ion channel regulator, may ameliorate the accelerated loss of lung function in CF patients during adolescence and has the potential to provide significant benefit in lung function for those patients on minimal pharmacotherapies.

“During adolescence, CF patients are especially vulnerable to an accelerated rate of decline in lung function and there is a consequent need for therapies that delay or reduce lung function loss in this population,” stated Richard B. Moss, M.D., Professor Emeritus of Pediatric Pulmonary Medicine at Stanford University School of Medicine and Co-Director of the Children’s Health Research Program at Stanford University Medical Center. “The significant lung function improvements observed in the subgroup of adolescent patients in the TIGER-1 clinical trial suggest the potential of denufosol as an early disease-stage intervention therapy that may reduce the loss of lung function during this critical time in a CF patient’s lung disease progression.”

The oral presentation, “Denufosol Improved Lung Function in Adolescent CF Patients” (R.B. Moss, A. Schaberg, C. Deans, W. Tian, L. Smiley, N. Herje, T. Durham, F.J. Accurso), is being presented during the session, “Workshop 5: Current Clinical Trials,” on Thursday, June 17 from 3:30 - 3:45 p.m. local time (9:30 - 9:45 a.m. ET). The presentation highlights subgroup data from the pre-specified analysis of adolescent CF patients aged 12-18 years old (n=123) from Inspire’s first Phase 3 clinical trial with denufosol, TIGER-1. In this trial, denufosol significantly improved lung function versus placebo in adolescents during the 24-week double-blind portion of TIGER-1 and continued improvement in lung function was observed with open-label treatment. The change from baseline in FEV₁ (Forced Expiratory Volume in One Second) for the adolescent patients treated with denufosol at the week-24 endpoint was 112 mL compared to -10 mL for placebo (p=0.013). In comparison, in the intent-to-treat (ITT) population in TIGER-1 (n=352), the change from baseline in FEV₁ at the 24-week endpoint was 48 mL for denufosol compared to 3 mL for placebo (p=0.047). The rate of decline in percent predicted FEV₁ for adolescent patients receiving placebo from week 0 to week 24 during the TIGER-1 trial was significantly different from zero (p <0.001;>1 for adolescent patients receiving denufosol was not significantly different from zero (p=0.134). The change from baseline for FEF_25%-75% (Forced Expiratory Flow), a measure of small airways function, for the adolescent patients treated with denufosol at the week-24 endpoint was 115 mL/sec. compared to -112 mL/sec. for placebo (p=0.036).

The Company is also presenting three additional posters at the ECFS Conference. The poster presentation, “Potential of Denufosol as an Early Intervention in CF Lung Disease: Efficacy in Patients with Minimal Pharmacotherapy in a U.S. Phase 3 Clinical Trial” (F.J. Accurso, W. Tian, A. Schaberg, T. Navratil, M.S. Howenstine, T.G.

Inspire Pharmaceuticals, Inc. announced today patient enrollment is complete in Denufosol

DURHAM, N.C.--(Business Wire)--
Inspire Pharmaceuticals, Inc. (NASDAQ: ISPH) announced today patient enrollment
is complete in three of its late-stage clinical trials.

"We are pleased to be executing on our strategic plan with the achievement of
these patient enrollment milestones in the clinical development programs for
denufosol, PROLACRIA and AZASITE®,as this places us in a position to have
top-line results from all our late-stage clinical programs within 18 months. We
would like to thank the dedicated clinical investigators, study coordinators and
patients who participated in our trials as well as the Cystic Fibrosis
Foundation and its affiliates for raising awareness of the importance of
participating in clinical trials," stated Benjamin R. Yerxa, Ph.D., Executive
Vice President and Chief, Research and Development.

Denufosol Tetrasodium for Cystic Fibrosis

Inspire announced today that TIGER-2, the Company`s second Phase 3 pivotal
clinical trial (Trial 08-110) with denufosol tetrasodium inhalation solution for
the treatment of cystic fibrosis (CF), has completed patient enrollment. TIGER-2
is a 48-week trial comparing 60 mg of denufosol to placebo, administered
three-times daily by jet nebulizer, in a targeted 450 CF patients. The Company
expects to have top-line results from TIGER-2 in the first quarter of 2011.

"We are excited that patient enrollment in TIGER-2 is complete. This is an
important step toward bringing this potential new treatment to cystic fibrosis
patients," said Robert J. Beall, Ph.D., President and CEO of the Cystic Fibrosis
Foundation. "Denufosol`s novel approach to treating the underlying ion channel
defect in CF lung disease makes it a promising therapy, and we look forward to
the results from this trial."


About Denufosol Tetrasodium

Denufosol tetrasodium is a first-in-class receptor-mediated chloride channel
activator that addresses the underlying ion transport defect in the lungs of
patients with cystic fibrosis (CF). Denufosol is designed to enhance airway
hydration and mucociliary clearance through receptor-mediated mechanisms that
increase chloride secretion, inhibit sodium absorption and increase ciliary beat
frequency. These integrated pharmacological actions are important to restoring
airway clearance, maintaining lung function, and potentially delaying the
progression of CF lung disease. Denufosol is targeted as an early intervention
therapy for CF lung disease. This product candidate has been granted orphan drug
and fast-track review status by the U.S. Food and Drug Administration (FDA) and
orphan drug status by the European Medicines Agency (EMEA).

About Inspire

Inspire is a biopharmaceutical company focused on researching, developing and
commercializing prescription pharmaceutical products for ophthalmic and
pulmonary diseases. Inspire`s goal is to build and commercialize a sustainable
portfolio of innovative new products based on its technical and scientific
expertise. The most advanced compounds in Inspire`s clinical pipeline are
PROLACRIA™ (diquafosol tetrasodium ophthalmic solution) 2% for dry eye and
denufosol tetrasodium for cystic fibrosis, which are both in Phase 3 development
and AZASITE® (azithromycin ophthalmic solution) 1% for blepharitis, which is in
Phase 2 development. Inspire receives revenues related to the promotion of
AZASITE for bacterial conjunctivitis, the co-promotion of ELESTAT® (epinastine
HCl ophthalmic solution) 0.05% for allergic conjunctivitis and royalties based
on net sales of RESTASIS® (cyclosporine ophthalmic emulsion) 0.05% for dry eye.
For more information, visit www.inspirepharm.com.


Inspire Pharmaceuticals, Inc.
Investor Contact:
Jenny Kobin, 919-941-9777, Extension 219
VP, Investor Relations and Corporate Communications
or
Media Contact:
Cara Amoroso, 919-941-9777, Extension 266
Manager, Corporate Communications

1st dose of Denufosol (or placebo)

I'm in clinic right now, doing my 1st dose of either placebo or Denufosol.

I'm coughing quite a bit - my hunch is I'm not on placebo (even HTS doesn't make me cough this much).

But we'll see. More info to come later.....

Denufosol's effect on sinusitis

Denufosol's effect on sinusitis


http://www.inspirepharm.com/pdfs/Inspire-ECFS2009-Mospan,Andrea-FINAL.pdf

Inspire (Denufosol) looking hard for partner

Inspire looking hard for partner

It needs help to sell drug overseas

By Alan M. Wolf - Staff Writer

Published: Fri, May. 08, 2009 02:00AM

Modified Thu, May. 07, 2009 10:01PM

The economic slump is hampering Inspire Pharmaceuticals' ability to attract a partner to help develop and eventually sell a promising experimental cystic fibrosis drug outside North America.

Consolidation in the pharmaceutical industry and the credit crisis have slowed negotiations with potential partners, Inspire CEO Christy Shaffer told analysts during a conference call Thursday morning.

"As you may have heard from other companies, the partnering dynamics have changed in the current economy," Shaffer said

Finding a partner is important because Inspire will need more money by next year to continue clinical testing on that drug and others. The Durham company had $55 million in cash and investments at the end of March, enough to fund operations until early 2010.

Without the financial backing of a partner, Inspire will be required to find other ways to raise money later this year, possibly by selling stock or borrowing, said Ian Sanderson, an analyst with Cowen and Co. That uncertainty will continue to hold down Inspire's stock, he added.

To cut costs and conserve cash, Inspire in March eliminated 20 jobs as it ended research on several early-stage experimental drugs. "For the rest of 2009, we will remain focused on managing our financial resources," Shaffer said.

The company now employs 227, about half in Durham.

The cystic fibrosis drug, known as denufosol, won't be widely available for at least two years, assuming it wins regulatory approval. Inspire would commercialize it in the United States, but wants a partner outside of North America.

The drug has performed well in clinical trials, helping people with cystic fibrosis breathe. Testing will continue for at least another year.

Inspire also reported Thursday that first-quarter revenue rose 47 percent to $14.3 million, boosted by increased sales of its drugs to treat pink eye and other eye diseases.

But as with other small drug-development companies in the Triangle, Inspire continues to lose money as it spends millions to test new medicines and find new uses for existing ones. The first-quarter loss of $19.4 million was an improvement from the loss of $25.9 million during the same period last year.

The results missed the average expectations of Wall Street analysts.

Inspire's shares fell 35 cents to close at $4.23 on Thursday. The stock is up 18 percent this year.

alan.wolf@newsobserver.com or 919-829-4572

Denufosol Update

Well, it's been nearly 2 months since I posted last about Denufosol.

My clinic was having serious issues with the clinical trial coordinator so we decided to postpone things until the New Year (and when I got back from traveling abroad).

Things were pushed back even more due to my recent hospitalization.

So I'm HOPING at my 2 week post-hospital follow up we'll be able to get things started with Denufosol. I'll keep you guys posted :)

1st Visit

Well I'm thrilled to report that I have started the TIGER II study - the 2nd Phase III trial of Inspire's Denufosol.

If you want to read about the TIGER I results, the 1st Phase III trial check out: http://www.medicalnewstoday.com/articles/126926.php

So today was the inclusion/exclusion visit. So they did the "what meds are you? what is your genotype? when were you diagnosed?" stuff. They also did:

• Blood Test
• Urine sample (test for pregnancy)
• Basic PFT (make sure FEV1 > 75%)
  

They sent me home with a nice stipend along with a daily diary to record how I'm feeling every night (are you tired? have you felt feverish? are you coughing a lot?).

So I guess I'll hear back in the next week or so if I fit all the criteria. I'm sure I'll be fine, but I guess they have to go through all the wonderful formalities :)

I'm pretty excited to get this party started. Of course I hope I don't get placebo but that's all part of the game, right? Placebo or drug, I'm still helping to get this drug on the market!

Stay tuned....