UTHR Terminates PERFECT TRIAL

[Thundersnow]

Sept 20, 2022 11:41:51 GMT -5 Clement said:

The 8K did not specifically mention the separate "PERFECT OLE" (open label extension) study, which is a separate clinical trial:

clinicaltrials.gov/ct2/show/NCT03794583?term=perfect&cond=ph+copd&draw=1&rank=1

"This open-label study will evaluate the safety of continued therapy with inhaled treprostinil in participants who have completed Study RIN-PH-304 (NCT03496623). This study hypothesizes that long-term safety findings will be similar to those observed in the randomized, placebo-controlled, double-blind, adaptive study 'A Phase 3, Randomized, Placebo-controlled, Double-blind, Adaptive Study to Evaluate the Safety and Efficacy of Inhaled Treprostinil in Patients with Pulmonary Hypertension due to Chronic Obstructive Pulmonary Disease (PH-COPD)(RIN-PH-304)."

I speculate that the termination of PERFECT does not imply termination of PERFECT OLE. Something good might be happening.

I don't get why UTHR would change the protocols of PERFECT last Qtr (after 4 years) and then Terminate the Study a month later?  Makes no sense and for them to remove from their website makes no sense either.....

I guess we will have to wait and see.

[Clement]

Recall that in the PERFECT trial, UTHR was blinded. But the independent DSMC was unblinded, ie, maybe they observed how well the non-placebo group was doing. It is possible the DSMC made suggestions to benefit the trial participants and it would be stupid for UTHR to ignore those suggestions.

It is considered unfair and cruel to put trial participants on placebo when results of the drug are very good.  These trial participants (PH-COPD) are on a march toward death.

But yeah, we will have to wait and see.

[Thundersnow]

Sept 20, 2022 15:03:00 GMT -5 Clement said:

Recall that in the PERFECT trial, UTHR was blinded. But the independent DSMC was unblinded, ie, maybe they observed how well the non-placebo group was doing. It is possible the DSMC made suggestions to benefit the trial participants and it would be stupid for UTHR to ignore those suggestions.

It is considered unfair and cruel to put trial participants on placebo when results of the drug are very good.  These trial participants (PH-COPD) are on a march toward death.

But yeah, we will have to wait and see.

Which is why they changed protocols last month.   They switched from Crossover to PARALLEL.  The change was built into the trial design so another words it was PRE-APPROVED by the FDA

I don't understand why UTHR HUNG EVERYONE OUT TO DRY with their filing today.  If it was an excellent outcome why not say it?  Why not issue a press release saying they stopped the trial due to exceeding expectations?

[lakers]

9/20/22 Long after first nod for inhaled Tyvaso, United Therapeutics scraps PhIII in PH with COPD
Af­ter a re­cent court win for its in­haled pul­monary ar­te­r­i­al hy­per­ten­sion drug, push­ing off com­pe­ti­tion for a few more years, Unit­ed Ther­a­peu­tics has qui­et­ly scrapped a late-stage study of Ty­va­so.

The Phase III ter­mi­na­tion oc­curred be­cause of a rec­om­men­da­tion from the da­ta safe­ty mon­i­tor­ing com­mit­tee “fol­low­ing a rou­tine safe­ty and ef­fi­ca­cy analy­sis,” Unit­ed said in an SEC fil­ing Tues­day morn­ing.

The bio­phar­ma first lined up FDA ap­proval of the in­haled drug in the sum­mer of 2009, for PAH. The drug pulled in $480 mil­lion in sales in 2020 and $607 mil­lion in 2021. Cowen an­a­lyst Joseph Thome has mod­eled rev­enues peak­ing at $1.6 bil­lion in 2025 for the in­haled fran­chise.

The culled Phase III was ob­serv­ing the drug in pa­tients with pul­monary hy­per­ten­sion due to chron­ic ob­struc­tive pul­monary dis­ease, or PH-COPD. Just ear­li­er this month, Unit­ed had pro­longed the tri­al’s pri­ma­ry com­ple­tion date, mov­ing it from Ju­ly 31, 2022, to Dec. 31, 2024, ac­cord­ing to an up­date to the fed­er­al tri­als data­base.

Unit­ed had ex­pect­ed to en­roll 314 pa­tients in­to the study, dubbed PER­FECT, which start­ed in June 2018. The com­pa­ny will take a look at the da­ta and plans to present the re­sults to sci­en­tists, ac­cord­ing to the SEC doc­u­ment.

It’s not the first time Unit­ed has run in­to trou­bles try­ing to ex­pand the la­bel for Ty­va­so, al­so known as tre­pros­tinil. In 2017, the com­pa­ny with­drew a Phase III study of the oral for­mu­la­tion in pa­tients with PH as­so­ci­at­ed with sick­le cell dis­ease. An­oth­er Phase III of the oral for­mu­la­tion was ter­mi­nat­ed in fall 2020, test­ing the drug in pa­tients with PH as­so­ci­at­ed with heart fail­ure with pre­served ejec­tion frac­tion.
endpts.com/long-after-first-nod-for-inhaled-tyvaso-united-therapeutics-scraps-phiii-in-ph-with-copd/

[saradm16]

clinicaltrials.gov/ct2/show/NCT03496623

it's nebulizer drug vs placeco in nebulizer

[agedhippie]

It seems unlikely this would impact the MNKD stock price in any way since it's no a DPI drug being tested. It is never good when the DSMC stops a trial because it either means there is a data accuracy issue, or a patient safety issue. Since they intend to present the data it looks likely that it is a safety issue. The ethics committee are the people who would stop the trial if the results were so good continuing couldn't be justified.

It is a financial hit for UTHR because of the trial costs, but nobody expects every label extension to be a winner and I expect UTHR will just shrug and move on.

[Thundersnow]

Sept 21, 2022 16:23:29 GMT -5 agedhippie said:

It seems unlikely this would impact the MNKD stock price in any way since it's no a DPI drug being tested. It is never good when the DSMC stops a trial because it either means there is a data accuracy issue, or a patient safety issue. Since they intend to present the data it looks likely that it is a safety issue. The ethics committee are the people who would stop the trial if the results were so good continuing couldn't be justified.

It is a financial hit for UTHR because of the trial costs, but nobody expects every label extension to be a winner and I expect UTHR will just shrug and move on.

It's really the OPTICS that has hurt MNKD.  It's a Derivative play....

I am perplexed over this.  UTHR changed the protocol last month which meant they were thinking about this for at least 3 months.  To ensure greater success of the trial they made the switch but then a month later they terminate the trial?   Martine and Mike were very positive on the trial and gave no hints a termination was coming.  Doesn't make sense.

[agedhippie]

Sept 21, 2022 16:51:05 GMT -5 Thundersnow said:

Sept 21, 2022 16:23:29 GMT -5 agedhippie said:

It seems unlikely this would impact the MNKD stock price in any way since it's no a DPI drug being tested. It is never good when the DSMC stops a trial because it either means there is a data accuracy issue, or a patient safety issue. Since they intend to present the data it looks likely that it is a safety issue. The ethics committee are the people who would stop the trial if the results were so good continuing couldn't be justified.

It is a financial hit for UTHR because of the trial costs, but nobody expects every label extension to be a winner and I expect UTHR will just shrug and move on.

It's really the OPTICS that has hurt MNKD.  It's a Derivative play....

I am perplexed over this.  UTHR changed the protocol last month which meant they were thinking about this for at least 3 months.  To ensure greater success of the trial they made the switch but then a month later they terminate the trial?   Martine and Mike were very positive on the trial and gave no hints a termination was coming.  Doesn't make sense.

At a guess (and only a guess) they knew there was an issue and wanted to make a protocol change to address things, but that didn't resolve the issue. They must have expected the change to fix the issue or they wouldn't have made it.

[cretin11]

aged that makes sense. But if by chance it was actually for a good reason UTHR terminated, then when would we likely find out for sure? Seems an announcement would’ve already happened but I don’t know.

[agedhippie]

Sept 22, 2022 11:21:14 GMT -5 cretin11 said:

aged that makes sense. But if by chance it was actually for a good reason UTHR terminated, then when would we likely find out for sure? Seems an announcement would’ve already happened but I don’t know.

If it was good news UTHR would be shouting it from the rooftops. As it is we know the stop came from the DCMS and the probability of that being good news is vanishingly small, a DCMS doesn't do good news.

[Thundersnow]

Sept 22, 2022 16:24:47 GMT -5 agedhippie said:

Sept 22, 2022 11:21:14 GMT -5 cretin11 said:

aged that makes sense. But if by chance it was actually for a good reason UTHR terminated, then when would we likely find out for sure? Seems an announcement would’ve already happened but I don’t know.

If it was good news UTHR would be shouting it from the rooftops. As it is we know the stop came from the DCMS and the probability of that being good news is vanishingly small, a DCMS doesn't do good news.

If it was bad news why submit the data to the scientific community?? I don't recall any company publish WHY THEY TERMINATED A TRIAL. 

[agedhippie]

Sept 22, 2022 18:38:12 GMT -5 Thundersnow said:

Sept 22, 2022 16:24:47 GMT -5 agedhippie said:

If it was good news UTHR would be shouting it from the rooftops. As it is we know the stop came from the DCMS and the probability of that being good news is vanishingly small, a DCMS doesn't do good news.

If it was bad news why submit the data to the scientific community?? I don't recall any company publish WHY THEY TERMINATED A TRIAL. 

There may be some secondary findings they want to use and that would need to be published. You can publish selectively so you don't have to publish everything. You cannot cherry pick from a data set, but you can publish the data for a secondary objective.

[uvula]

Maybe they want everyone to know the safety issue was not with the drug itself but the nebulizer delivery system. Pure speculation on my part.