United Therapeutics Announces the Publication of Tyvaso DPI™

[hellodolly]

Apr 06, 2022 / 6:00 AM ET

PRESS RELEASE

In subjects with PAH, transition from Tyvaso® to Tyvaso DPI™ demonstrated safety and tolerability with significant improvements in six-minute walk distance, device preference and satisfaction, and patient reported outcomes



Tyvaso DPI safety confirmed through 51 weeks of optional extension phase data with no study drug-related serious adverse events



FDA action on the New Drug Application for Tyvaso DPI is expected by May 2022



SILVER SPRING, Md. & RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)-- United Therapeutics Corporation (Nasdaq: UTHR), a public benefit corporation, today announced the publication of additional clinical and long-term safety data from the BREEZE study evaluating Tyvaso DPI™ (treprostinil) in patients with pulmonary arterial hypertension (PAH) in the journal Pulmonary Circulation.



The publication evaluated the BREEZE study and its ongoing optional extension phase (OEP), and concluded:



Tyvaso DPI’s delivery device, along with the clinical results from BREEZE, may facilitate the introduction of inhaled treprostinil earlier in the clinical course of PAH for appropriate patients;

Doses of Tyvaso DPI above the current recommended dose of nebulized Tyvaso (9-12 breaths four times daily) were well tolerated, potentially allowing for titration to higher dose levels without resulting in prolonged treatment sessions;

A simplified dosing regimen could potentially increase patient compliance; and

Tyvaso DPI has a pharmacokinetic (PK) profile comparable to nebulized Tyvaso, such that patients will not have to use more drug than nebulized Tyvaso to get the same treprostinil blood concentration or treatment effect.

We’re thrilled that this manuscript builds on earlier data presented at the European Respiratory Society’s 2021 International Congress, with additional long-term follow-up data that continues to show a strong safety profile for patients transitioning from nebulized Tyvaso to Tyvaso DPI,” said Peter Smith, PharmD, Vice President, Product Development, at United Therapeutics. “The optional extension phase is still ongoing, and we’ve accrued over 71 patient-years of experience with Tyvaso DPI.”

Source:https://ir.unither.com/news/press-releases/press-release-details/2022/United-Therapeutics-Announces-the-Publication-of-Tyvaso-DPI-BREEZE-Clinical-and-Long-term-Data-in-the-Journal-Pulmonary-Circulation/default.aspx

[jkendra]

www.biospace.com/article/releases/united-therapeutics-announces-the-publication-of-tyvaso-dpi-breeze-clinical-and-long-term-data-in-the-journal-pulmonary-circulation/



United Therapeutics Announces the Publication of Tyvaso DPI™ BREEZE Clinical and Long-term Data in the Journal Pulmonary Circulation


Published: Apr 06, 2022



In subjects with PAH, transition from Tyvaso® to Tyvaso DPI™ demonstrated safety and tolerability with significant improvements in six-minute walk distance, device preference and satisfaction, and patient reported outcomes

Tyvaso DPI safety confirmed through 51 weeks of optional extension phase data with no study drug-related serious adverse events

FDA action on the New Drug Application for Tyvaso DPI is expected by May 2022

SILVER SPRING, Md. & RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)-- United Therapeutics Corporation (Nasdaq: UTHR), a public benefit corporation, today announced the publication of additional clinical and long-term safety data from the BREEZE study evaluating Tyvaso DPI™ (treprostinil) in patients with pulmonary arterial hypertension (PAH) in the journal Pulmonary Circulation.



The publication evaluated the BREEZE study and its ongoing optional extension phase (OEP), and concluded:



Tyvaso DPI’s delivery device, along with the clinical results from BREEZE, may facilitate the introduction of inhaled treprostinil earlier in the clinical course of PAH for appropriate patients;

Doses of Tyvaso DPI above the current recommended dose of nebulized Tyvaso (9-12 breaths four times daily) were well tolerated, potentially allowing for titration to higher dose levels without resulting in prolonged treatment sessions;

A simplified dosing regimen could potentially increase patient compliance; and

Tyvaso DPI has a pharmacokinetic (PK) profile comparable to nebulized Tyvaso, such that patients will not have to use more drug than nebulized Tyvaso to get the same treprostinil blood concentration or treatment effect.

Tyvaso DPI is a next-generation dry powder formulation of Tyvaso, which is currently undergoing review by the U.S. Food and Drug Administration (FDA). If approved, Tyvaso DPI is expected to provide a more convenient method of administration as compared with traditional nebulized Tyvaso therapy.



“If approved, I believe Tyvaso DPI could represent a very exciting addition to the treatment paradigm for the PAH population,” said Leslie Spikes, M.D., Associate Professor of Pulmonary and Critical Care Medicine at the University of Kansas Medical Center. “The ease of use, portability, and ability to titrate the dose with Tyvaso DPI should have a beneficial impact on patient compliance and persistence and could result in improved exercise ability.”



“We’re thrilled that this manuscript builds on earlier data presented at the European Respiratory Society’s 2021 International Congress, with additional long-term follow-up data that continues to show a strong safety profile for patients transitioning from nebulized Tyvaso to Tyvaso DPI,” said Peter Smith, PharmD, Vice President, Product Development, at United Therapeutics. “The optional extension phase is still ongoing, and we’ve accrued over 71 patient-years of experience with Tyvaso DPI.”



The BREEZE study



The BREEZE study enrolled 51 subjects on a stable regimen of Tyvaso who were transitioned to Tyvaso DPI at a corresponding treprostinil dose. The primary objective of the study was to evaluate the safety and tolerability of Tyvaso DPI during a three-week treatment phase in PAH patients previously treated with Tyvaso Inhalation Solution; the majority of patients in the study were on dual background PAH therapies.



Top line data showing the BREEZE study met its primary objective were released in January 2021 and clinical data was presented at the European Respiratory Society International Congress in September 2021.



Secondary objectives of the study included changes in six-minute walk distance (6MWD), device preference and satisfaction as evaluated through the Preference Questionnaire for Inhaled Treprostinil Devices (PQ-ITD), and patient reported PAH symptoms and impact (PAH-SYMPACT®).



Primary safety and tolerability objective. Transition from Tyvaso to Tyvaso DPI demonstrated safety and tolerance. Forty-nine out of 51 patients (96%) completed the three-week treatment phase, while two subjects discontinued due to treatment-related adverse events during the treatment phase. There were no study drug-related serious adverse events. Most adverse events experienced during the study were mild to moderate in severity and occurred at severities and frequencies consistent with those seen in other inhaled treprostinil studies in patients with PAH. Please see Important Safety Information about Tyvaso at the end of this press release.



Secondary objectives. Three weeks after switching from Tyvaso to Tyvaso DPI, patients in the BREEZE study demonstrated:



Significant improvements in 6MWD compared to baseline. Improvements of 11.5 meters (p=0.0217) in 6MWD compared to baseline were observed through the three-week treatment phase;

Significant improvements in overall satisfaction with the Tyvaso DPI inhaler. Using the PQ-ITD, significant improvements (p<0.0001) were observed in overall satisfaction with the Tyvaso DPI inhaler; and

Significant improvements in PAH impact. The SYMPACT questionnaire includes domains on physical impacts, cognitive/emotional impacts, cardiopulmonary symptoms, and cardiovascular symptoms. Significant improvements in PAH impacts were observed in physical impacts (p=0.0438) and cognitive/emotional impacts (p=0.0048) at week three as well as physical impacts (p=0.0429) at week 11.

Pharmacokinetic results. Systemic exposure between the nebulized Tyvaso and Tyvaso DPI was comparable between the two formulations. Between-subject variability for area under the curve (AUC) and peak serum concentration (C­max) parameters was similar across dose levels for each formulation (Tyvaso or Tyvaso DPI). However, variability of AUC and C­max was 2- to 3-fold lower for Tyvaso DPI when compared to Tyvaso.



Optional extension phase. Subjects in BREEZE were given the opportunity to continue in an OEP. All subjects who completed the treatment phase (49/51) elected to continue in the OEP. At the July 2021 data cutoff for this manuscript, 17 patients had reached 51 weeks of Tyvaso DPI use and 39 patients were still participating in the OEP, but not all patients had reached the 51-week visit at the cut-off. Additional data from the OEP also demonstrated:



Long-term safety. Most patients in the OEP either maintained or increased their study dose from baseline and there were no treatment-related serious adverse events; and

Long-term efficacy. Improvements in 6MWD were sustained for patients in the OEP up to week 51 at the data cut-off date.

The manuscript, entitled “BREEZE: Open-label Clinical Study to Evaluate the Safety and Tolerability of Treprostinil Inhalation Powder as Tyvaso DPI in Patients With Pulmonary Arterial Hypertension,” is available on the Pulmonary Circulation Journal website and at doi.org/10.1002/pul2.12063.

[dh4mizzou]

A nit I'm sure but when the announcement says "... by May 2022" does that imply, as I would presume, by May 1st or by the END of May?

[anderson]

Is UTHR getting ready to fight the FDA in case of another delay? Do all NDAs go before an Advisory Committee? If not how did MNKD get Afrezza to end up before an FDA Advisory Committee where you could actually see the docs recommend approval or not?

[uvula]

When Marketing says something will be available in May, they want you to think it is the beginning of May. When Engineering says something will be available in May, they mean by the end of May. Ambiguity is always intentional.

It will be available in May.

[hellodolly]

Apr 6, 2022 8:42:37 GMT -5 anderson said:

Is UTHR getting ready to fight the FDA in case of another delay? Do all NDAs go before an Advisory Committee? If not how did MNKD get Afrezza to end up before an FDA Advisory Committee where you could actually see the docs recommend approval or not?

Have to ask cause I always miss these things...is your question based on the announcement by UTHR that the study was published?  Trying to see the nexus between a journal publication and the FDA approval.

[hellodolly]

Apr 6, 2022 8:43:34 GMT -5 uvula said:

When Marketing says something will be available in May, they want you to think it is the beginning of May. When Engineering says something will be available in May, they mean by the end of May. Ambiguity is always intentional.

It will be available in May.

...or, is it really after April 30 and before June 1? That deserves some sort of speculation.

[oldfishtowner]

"we’ve accrued over 71 patient-years of experience with Tyvaso DPI"

That statement jumped out at me.  Not sure why UTHR decided to emphasize that.  This was a very small study compared with a typical phase 3 trial that has 200 to 500 or more participants that would have provided many times the patient-years of experience than the BREEZE study did (even with the extension).  It seems to me that the real question is: is 71 patient-years meaningful to the FDA?  And what is the likelihood of the FDA requiring a full phase 3 study that would take another year or two to complete?

Anyone have enough knowledge about these things to provide some insight?

[Deleted]

Apr 6, 2022 9:11:57 GMT -5 oldfishtowner said:

"we’ve accrued over 71 patient-years of experience with Tyvaso DPI"

That statement jumped out at me.  Not sure why UTHR decided to emphasize that.  This was a very small study compared with a typical phase 3 trial that has 200 to 500 or more participants that would have provided many times the patient-years of experience than the BREEZE study did (even with the extension).  It seems to me that the real question is: is 71 patient-years meaningful to the FDA?  And what is the likelihood of the FDA requiring a full phase 3 study that would take another year or two to complete?

Anyone have enough knowledge about these things to provide some insight?

I think it's a very smart move.   They are telling the FDA the patients have a COMBINED amount of time dealing with PAH.  That's more than enough to express confidence in DPI.  Brilliant move! 

[hellodolly]

Apr 6, 2022 9:49:12 GMT -5 @chuckbass said:

Apr 6, 2022 9:11:57 GMT -5 oldfishtowner said:

"we’ve accrued over 71 patient-years of experience with Tyvaso DPI"

That statement jumped out at me.  Not sure why UTHR decided to emphasize that.  This was a very small study compared with a typical phase 3 trial that has 200 to 500 or more participants that would have provided many times the patient-years of experience than the BREEZE study did (even with the extension).  It seems to me that the real question is: is 71 patient-years meaningful to the FDA?  And what is the likelihood of the FDA requiring a full phase 3 study that would take another year or two to complete?

Anyone have enough knowledge about these things to provide some insight?

I think it's a very smart move.   They are telling the FDA the patients have a COMBINED amount of time dealing with PAH.  That's more than enough to express confidence in DPI.  Brilliant move! 

Especially, considering life expectancy without treatment.

[Clement]

Case 1: Suppose you have 500 patients on a drug for one tenth of a year each patient. That's 50 patient-years.

Case 2: Suppose you have 50 patients on the same drug for a year. That's 50 patient-years.

The BREEZE trial itself was short but with the optional extension phase we got a lot of safety data.

[cretin11]

Apr 6, 2022 8:37:30 GMT -5 dh4mizzou said:

A nit I'm sure but when the announcement says "... by May 2022" does that imply, as I would presume, by May 1st or by the END of May?

It means between now and the end of May.

[sr71]

Or it could be in May 2022 in one or more parallel universes, which may or may not affect OUR universe.

[harryx1]

[boca1girl]

Apr 6, 2022 10:17:19 GMT -5 cretin11 said:

Apr 6, 2022 8:37:30 GMT -5 dh4mizzou said:

A nit I'm sure but when the announcement says "... by May 2022" does that imply, as I would presume, by May 1st or by the END of May?

It means between now and the end of May.

I agree that it could be approved even before May.