MannKind Successfully Completes Phase 1 Trial of Nintedanib

[hellodolly]

MannKind Successfully Completes Phase 1 Trial of Nintedanib DPI for Pulmonary Fibrotic Diseases


11/04/24

PDF Version

Met primary objective demonstrating nintedanib DPI was safe and well tolerated

Participants did not experience adverse events typically reported with oral nintedanib

Expect to meet with the FDA in 1H 2025 to advance MNKD-201 into the next phase of development

DANBURY, Conn. and WESTLAKE VILLAGE, Calif., Nov. 04, 2024 (GLOBE NEWSWIRE) -- MannKind Corporation (Nasdaq: MNKD), a company focused on the development and commercialization of innovative inhaled therapeutic products and devices for patients with endocrine and orphan lung diseases, today announced the successful completion of its first-in-human Phase 1 study of nintedanib DPI (MNKD-201) for pulmonary fibrotic diseases, including idiopathic pulmonary fibrosis (IPF).



“These compelling results support advancing the development of nintedanib DPI for patients living with IPF, a chronic and progressive fibrotic lung disease with limited treatment options,” said Michael Castagna, PharmD, Chief Executive Officer for MannKind Corporation. “We look forward to discussing the Phase 1 trial results and our proposed late-stage development program at an end of phase 1 meeting with the FDA, planned for the first half of 2025.”



The key highlights of the study included:



Nintedanib DPI was shown to be safe and well tolerated in healthy volunteers with the tested doses and study duration

Participants did not experience typical adverse events seen with oral nintedanib; specifically, no GI or neurologic adverse events (AEs) were reported

Two types of AEs noted - cough and drop in FEV-1

These AEs were mild, transient, and fully recovered

These AEs were not dose-dependent and there was no pattern of recurrence or worsening with repeated dosing

No bronchospasm, wheezing, other symptoms, or change in vital signs were reported

No serious adverse events or study drug discontinuation

The completed Phase 1 was a single-site, randomized, placebo-controlled, single- (n=24) and multiple-ascending dose (n=16) study in healthy adult (older than 40 years old) participants. The primary objective of the study was to evaluate the safety and tolerability of nintedanib DPI. The secondary study objective was to evaluate the pharmacokinetics (PK) of MNKD-201.



“We are encouraged by the findings from this Phase 1 study of nintedanib DPI,” said Dr. Wassim Fares, MSc, FCCP, Senior Vice President, Therapeutic Area Head, Orphan Lung Diseases for MannKind Corporation. “Building on the known efficacy of oral nintedanib for IPF, delivery of a dry powder formulation directly to the lungs could potentially treat the disease while reducing the common adverse effects associated with oral delivery of nintedanib. Pending late-stage development trials, nintedanib DPI could offer an alternative and/or addition to current IPF therapies.”



Additionally, the preclinical chronic toxicology study did not show any adverse findings and supports further development of nintedanib DPI.

[Clement]

^ Beautiful news!  Just what we wanted and expected.

MC said, “We look forward to discussing the Phase 1 trial results and our proposed late-stage development program at an end of phase 1 meeting with the FDA, planned for the first half of 2025.”

I wonder why the development program meeting with FDA is for 1st half 2024. Why not sooner? Time for dealing with a potential partner who would take over further trials?

Just speculating.

[bthomas55ep]

Nov 4, 2024 8:46:53 GMT -5 Clement said:

^ MC said, “We look forward to discussing the Phase 1 trial results and our proposed late-stage development program at an end of phase 1 meeting with the FDA, planned for the first half of 2025.”

I wonder why the development program meeting with FDA is for 1st half 2024. Why not sooner? Time for dealing with a potential partner who would take over further trials?

Just speculating.

I was thinking the same thing! Wait until the first 1/2 of 2025 to sit down with the FDA on Phase II trial design? We do know BI has OFEV under patent until Spring of 2026, but even if the trials moved as fast as they could possibly move, Mannkind couldn't get it approved in the 1st half of 2026. Perhaps someone like BI is going to be involved and Mannkind expects them to be in trial design discussions too? Who knows? I guess we'll hear a comment or two about in during the 3Q conference call.

[uvula]

Googled it so you won't have to:
FEV1 stands for forced expiratory volume in one second, and it's a measurement of how much air a person can exhale in the first second after a full breath.

[hellodolly]

BI IPF PHIII Study:

www.boehringer-ingelheim.com/human-health/lung-diseases/pulmonary-fibrosis/nerandomilast-primary-endpoint-phase-3-fibroneer-ipf#:~:text=Nerandomilast%20was%20granted%20FDA%20Breakthrough,(IPF)%20in%20February%202022.

Topline data from FIBRONEER™-IPF show that the investigational compound nerandomilast met its primary endpoint, which was the absolute change from baseline in Forced Vital Capacity [mL] at week 52 versus placebo.
The FIBRONEER™-IPF trial is the largest trial in idiopathic pulmonary fibrosis (IPF) conducted to date. Patients were recruited in over 330 sites and in over 30 countries.1,5
Full efficacy and safety data from the trial will be presented in the first half of 2025.
Boehringer Ingelheim will submit a new drug application for nerandomilast for the treatment of IPF to the US FDA and other Health Authorities worldwide.

I suspect a similar trial for MNKD?

A Double Blind, Randomized, Placebo-controlled Trial Evaluating the Efficacy and Safety of nerandomilast Over at Least 52 Weeks in Patients With Idiopathic Pulmonary Fibrosis (IPF).



Primary endpoint: Absolute change from baseline in Forced Vital Capacity (FVC) (mL) at Week 52.



Key secondary endpoint:



Time to the first occurrence of any of the components of the composite endpoint: time to first acute IPF exacerbation; first hospitalization for respiratory cause; or death (whichever occurs first) over the duration of the trial.

Participants are put into 3 groups randomly, which means by chance. Participants in 2 groups take different doses of nerandomilast as tablets twice a day. Participants in the placebo group take placebo tablets twice a day. Placebo tablets look like nerandomilast tablets but do not contain any medicine.



The trial has been conducted in more than 30 countries,1 and randomized 1177 patients.

[prcgorman2]

Nov 4, 2024 9:43:38 GMT -5 uvula said:

Googled it so you won't have to:
FEV1 stands for forced expiratory volume in one second, and it's a measurement of how much air a person can exhale in the first second after a full breath.

FEV1 is a common test with an inexpensive test instrument called a spirometer.  It's also required before prescribing Afrezza inhalable insulin.  I think it's used to avoid prescribing to people with asthma or COPD, and also to be able to measure any decrease in lung capacity after having been using Afrezza for some time.

[cretin11]

Nov 4, 2024 9:43:38 GMT -5 uvula said:

Googled it so you won't have to:
FEV1 stands for forced expiratory volume in one second, and it's a measurement of how much air a person can exhale in the first second after a full breath.

That's right.  It's an important reading for pulmonary fibrosis, though probably second in importance to FVC.  IPF patients typically have reduced values in both categories (definitely in FVC).

The next most relevant reading is probably the FVC/FEV ratio.  Opposite of the other two readings above, typically you see a higher number for the "ratio" in pulmonary fibrosis cases.  If the ratio is lower, that points more to an obstructive lung disease, usually COPD (caused by cigarettes, cotton dust, etc.).  IPF is a restrictive lung disease rather than obstructive.

But that's more than we need to know about PFTs (pulmonary function tests), and we haven't even touched on DLCO readings yet...

Bottom line these trial results are good for us.

[Thundersnow]

I'm expecting a partner announcement within 90-120 days for DPI version.  If you're planning to have meetings with the FDA you want all parties there.

That's the only reason why FDA meeting is 1H25.   

[radgray68]

At first read, I thought 1st half 2025 was quite a while but remember we’re still waiting for chronic toxicology data in Q4 to include in our discussion/submission.

[mpg54]

Nov 4, 2024 15:49:06 GMT -5 Thundersnow said:

I'm expecting a partner announcement within 90-120 days for DPI version.  If you're planning to have meetings with the FDA you want all parties there.

That's the only reason why FDA meeting is 1H25.   

Is a partner definitely the better course here? Despite the success with UTHR I’m still weary of partnerships, or just getting a small cut in the end. There is something appealing to 100% of the Revenue. I am fully aware there’s a significant cost to that also, but a large Revenue # sure does wonders for Market value.

[cretin11]

Pros and cons either way, but I'm with Thundersnow on this. Let's get the partnership deal negotiated. We should hopefully have a much better arrangement than was negotiated with UTHR (not complaining about that, we needed it desperately and UTHR knew it too, we'd be in a world of hurt had we blown that opportunity IMO). Our painful track record trying to commercialize drugs doesn't need to be rehashed here. While 100% of revenue has some appeal, I believe our market cap will react more favorably if we ink a robust royalty partnership arrangement with a company that does know how to competently commercialize the product. And then we can stay "in our lane" which should be focused on the Technosphere pipeline and stacking royalties. Our stated goal is launching one product from our pipeline every year. That is the math I'm interested in doing.

[mpg54]

Nov 4, 2024 16:44:32 GMT -5 cretin11 said:

Pros and cons either way, but I'm with Thundersnow on this. Let's get the partnership deal negotiated. We should hopefully have a much better arrangement than was negotiated with UTHR (not complaining about that, we needed it desperately and UTHR knew it too, we'd be in a world of hurt had we blown that opportunity IMO). Our painful track record trying to commercialize drugs doesn't need to be rehashed here. While 100% of revenue has some appeal, I believe our market cap will react more favorably if we ink a robust royalty partnership arrangement with a company that does know how to competently commercialize the product. And then we can stay "in our lane" which should be focused on the Technosphere pipeline and stacking royalties. Our stated goal is launching one product from our pipeline every year. That is the math I'm interested in doing.

I'm not sure what the right path is, ultimaltely whatever builds the biggest possible Market Valuation in the next 2-4 years I'm good with.  I do think that eventually becoming a BP is a better path, but maybe that does take to much time and pain to get there.  I liked Bezos idea that a book store was not the ultimate goal, but then again we've waited long enough and I'm not waiting 10 years on MNKD to find out.  

[anderson]

Dont think there is a real reason to hurry due to patent expiration in 2026. Especially if this is a II/III trial. Should shoot for late 2026 FDA approval.
www.greyb.com/blog/ofev-patent-expiration/
Composition of Matter US6762180B1
Expires on Apr 01, 2026

[Thundersnow]

Nov 4, 2024 16:11:24 GMT -5 mpg54 said:

Nov 4, 2024 15:49:06 GMT -5 Thundersnow said:

I'm expecting a partner announcement within 90-120 days for DPI version.  If you're planning to have meetings with the FDA you want all parties there.

That's the only reason why FDA meeting is 1H25.   

Is a partner definitely the better course here? Despite the success with UTHR I’m still weary of partnerships, or just getting a small cut in the end. There is something appealing to 100% of the Revenue. I am fully aware there’s a significant cost to that also, but a large Revenue # sure does wonders for Market value.

I agree 1000%.  It's best for MNKD to hold onto the asset but what can happen if they do??  Could B-I sue them for patent infringement?  I know the patent expires in 2026 but you know corporations.  They will sue just to sue and delay everything for years.  So will it benefit them to make a strong deal with the OWNER/Market Leader or not? 

With the success of Tyvaso DPI, MNKD is in a strong position to negotiate a great deal.  Also I believe this is why Binder is on the BOD.  Mike values his expertise and experience in negotiating deals. 

Who knows maybe UTHR will jump in and want to partner with MNKD.  At least they will have muscle against B-I and at the minimum MNKD can play UTHR off of B-I and really get a good deal.


Let's see what happens early next year.  

[prcgorman2]

Mike made a comment during a Q&A earlier this year that UTHR had first right of refusal (essentially) for the development of nintedanib DPI and passed on it which was the green light for MannKind to go it alone. MannKind also had a slide earlier this year with a citation showing Ofev (oral) medication is currently worth $4B+ in revenue and will be north of $7B by 2030. MannKind’s nintedanib DPI Phase 1 has already shown what we hoped for which is a lack of the oral med side-effects which are so horrible patients would rather experience IPF than take Ofev. Assuming Phase II/III prove the rest that’s needed for approval by the FDA, who gets marketing rights can get worked out over time. Not sure if there is a significant cost for PhII/III trials but if MannKind can shoulder the burden, going it alone for now may improve their negotiations later. To me it seems obvious those negotiations will happen, and the only question is how they turn out.