Ofev Slows Scarring in Pulmonary Fibrosis Patients’ Lungs, Phase 3b Trial Shows

Ofev Slows Scarring in Pulmonary Fibrosis Patients’ Lungs, Phase 3b Trial Shows

Boehringer Ingelheim’s Ofev (nintedanib) slows scarring in idiopathic pulmonary fibrosis patients’ lungs, a Phase 3b trial indicates.

The company used an imaging technique to check on Ofev’s anti-fibrotic properties. It was the first time it had used high-resolution computerized tomography, or HRCT, to do this with IPF patients.

Boehringer presented the results at the Pulmonary Fibrosis Foundation Summit in Nashville, Nov. 9-11. The presentation was titled “Effect of nintedanib on disease progression: results from a Phase IIIb trial in patients with idiopathic pulmonary fibrosis (IPF).

Researchers used HRCT to measure both lung scarring and tissue thickening — hallmarks of fibrosis.

The primary objective of the trial (NCT01979952) was to see if Ofev would improve patients’ scores on a lung fibrosis index after six months of treatment. Researchers randomly assigned patients to either 150 mg of Ofev twice a day or a placebo.

The average fibrosis score of the Ofev-treated patients was 11.4 percent after six months, versus 14.6 percent for the placebo group. The difference of 3.2 percentage points in the scores was not statistically significant but did show Ofev’s potential for halting fibrosis progression.

“With the aid of high-resolution CT scans, we have observed a reduction in the progression of lung fibrosis with Ofev versus placebo,” Dr. Lisa Lancaster, director of the Interstitial Lung Disease Program at Vanderbilt University Medical Center, said in a press release. She was the study’s lead investigator.

“These encouraging results demonstrate that through an imaging scan we identified differential responses in fibrotic changes between groups that will help doctors make informed treatment decisions,” Lancaster added.

Researchers also looked at changes in patients’ lung function, using a measure known as forced vital capacity. FVC is the amount of air a person can exhale after a deep breath.

After six months, the placebo group’s FVC scores were much lower than the Ofev group’s — that is, the control group could exhale much less air than the treated group. This indicated that lung function decline was greater in the placebo group.

The results matched those from four previous trials — the Phase 2 TOMORROW (NCT00514683) study, the Phase 3 INPULSIS studies (NCT01335464 and NCT01335477), and the INPULSIS-ON extension study (NCT01619085). The trials also showed that Ofev-treated patients ended up with better lung function than placebo patients.

“This [latest] study reaffirms the beneficial effect of Ofev for reducing lung function decline and slowing disease progression,” said Dr. Thomas Leonard, executive director of Boehringer Ingelheim’s Clinical Development and Medical Affairs Specialty Care program. The trial was also “the first to suggest that there may be a differential effect of Ofev treatment versus placebo in lung fibrosis change,” he said.

“We look forward to presenting additional findings from this study at major medical congresses next year and confirmation of these results in future studies,” Leonard added.

Both the U.S. Food and Drug Administration and the European Union have approved Ofev as a treatment for idiopathic pulmonary fibrosis.

One comment

  1. ric ellens says:

    OFEV i heard works best with PBI-4050 from Prometic Life Science

    LAVAL, QC, Sept. 25, 2017

    Prometic moving immediately to formalize enrollment of specialist clinical sites across the United States
    U.S. IND to be followed by clinical trial applications in Canada, Europe, Australia and Japan throughout Q4 2017
    Prometic plans to supplement the IND with a protocol for a study of PBI-4050 monotherapy in IPF patients in October 2017

    LAVAL, QC, Sept. 25, 2017 /CNW Telbec/ – Prometic Life Sciences Inc. (TSX: PLI) (OTCQX: PFSCF) (Prometic) today announced that its oral anti-fibrotic lead drug candidate, PBI-4050, has received U.S. Food and Drug Administration Investigational New Drug (IND) approval to commence its pivotal Phase 2/3 clinical trial in patients suffering from idiopathic pulmonary fibrosis (IPF).

    The pivotal Phase 2/3 clinical trial is a two-stage adaptive, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of PBI-4050 when combined with nintedanib (OFEV™, Boehringer Ingelheim) in subjects with IPF. The number of subjects required to be enrolled has been based on the results seen in the recently-completed open label study of PBI-4050 in IPF. The Phase 2 stage will enroll 375 subjects with IPF, who will be randomly assigned to one of three groups: 1) 125 subjects who will receive placebo + nintedanib, 2) 125 subjects who will receive PBI-4050 800 mg + nintedanib or 3) 125 subjects with PBI-4050 1200 mg + nintedanib. An independent Data and Safety Monitoring Board (DSMB) will conduct an interim 26-week analysis, and based on the safety and efficacy results, will recommend whether the study should continue into Phase 3 stage and which dose of PBI-4050 should be continued. This Phase 3 stage would randomize an additional up to 450 subjects to receive nintedanib plus either placebo or the chosen PBI-4050 dose.

    Prometic has already completed an open label Phase 2 study in patients who received PBI-4050 for 12 weeks in addition to either pirfenidone, nintedanib, or placebo. The study showed the Forced Vital Capacity (FVC) remained stable in patients on PBI-4050 alone (n=9, FVC -12 ml) and in patients on PBI-4050 in combination with nintedanib (n=15, FVC +2 ml). In contrast, the FVC declined significantly in patients receiving PBI-4050 in combination with pirfenidone (n=16, FVC -105 ml). PBI-4050’s plasma concentration was sub-therapeutic at 50% of the expected level in patients receiving PBI-4050 in combination with pirfenidone, suggesting a drug-drug interaction.

    “We are very encouraged by the results of our open-label trial of PBI-4050 in combination with nintedanib, and are pleased to advance the clinical development plan with this pivotal study”, said Dr. John Moran, Prometic’s Chief Medical Officer. “IPF is a very serious condition and we believe that patients may benefit from this novel therapeutic approach. We have multiple key opinion leaders who have expressed a wish to participate in the study, and now that the IND has been cleared we can begin a formal study startup”.

    Pierre Laurin, Prometic’s President and Chief Executive Officer, stated, “We are very excited to be entering the pivotal stages of our IPF clinical program, which is another important milestone towards bringing this therapy to patients who suffer from IPF. We believe that PBI-4050 is an important advancement in this indication and represents a potential significant step forward for helping patients

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