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Post by prcgorman2 on May 23, 2024 13:02:33 GMT -5
Best case for approval is 6 months (shorter review period) after Estimated Primary Completion Date of August 1, 2026? I assume 8/1/26 is on the paperwork, but I also thought MC said during the most recent EC, initial readout could be Q1 2025 (because they’re supposed to begin enrolling patients in June) and that it is possible 100% enrollment would be achieved by the time of the readout. (Would love to have that confirmed without having to listen to the EC again). I think the treatment lasts about 6 months. So maybe mid-2026 for FDA approval (if they use all of their permitted “Fast Track” 6 months). I’m not very knowledgeable of the process and timelines so caveat emptor. |
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Post by agedhippie on May 23, 2024 13:26:46 GMT -5
^This They extension is because they want to see the percentages of cases where NTM reoccurs because that is a current problem. This is the problem you see where the infection drops to low levels, but is not eliminated and reoccurs over time. There are existing oral versions of clofazimine that would be the competition for 101 and will probably limit the price that can be charged at scale (there are always corner cases where the oral absolutely cannot be used for which a high price can be supported.) Curious what role the current SAE's being mentioned by Mike are included with the oral versions? Was it 101 that was once used for leprosy and has many reported side affects? Mike feels with the new intervention lasting only six months, this reduces the systemic tox levels and thus, he expects more patient levels of compliance? If so, who will champion 101 as better than orals? MNKD? Clofazimine is already a treatment for NTM, just not a favored one as it is off-label. There are established antibiotics that are currently the first line drugs, but as the NTM variants become drug resistant they are less effective. The idea is that clofazimine is a newer line of attack that will encounter less drug resistance but at the price point that is being talked about I can see payers wanting it to be a step therapy. The issue for 101 is going to be that if MNKD establishes clofazimine as a viable option then the oral version of clofazimine will be considered again and that will create price pressure. There are also trials ongoing for new oral drugs like omadacycline although their timeline is beyond 101. |
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Post by agedhippie on May 23, 2024 13:31:56 GMT -5
Best case for approval is 6 months (shorter review period) after Estimated Primary Completion Date of August 1, 2026? I assume 8/1/26 is on the paperwork, but I also thought MC said during the most recent EC, initial readout could be Q1 2025 (because they’re supposed to begin enrolling patients in June) and that it is possible 100% enrollment would be achieved by the time of the readout. (Would love to have that confirmed without having to listen to the EC again). I think the treatment lasts about 6 months. So maybe mid-2026 for FDA approval (if they use all of their permitted “Fast Track” 6 months). I’m not very knowledgeable of the process and timelines so caveat emptor. The initial readout is to decide it the trial can continue and is usually around the halfway mark. They are looking to see if there is a significant number of problems with the protocol and if they need to restart. Results from the read out are considered interesting, but not significant as only part of the cohort will have completed the trial (the bad outcomes may all be lurking in the second half). |
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Post by agedhippie on May 23, 2024 13:41:00 GMT -5
^This They extension is because they want to see the percentages of cases where NTM reoccurs because that is a current problem. This is the problem you see where the infection drops to low levels, but is not eliminated and reoccurs over time. There are existing oral versions of clofazimine that would be the competition for 101 and will probably limit the price that can be charged at scale (there are always corner cases where the oral absolutely cannot be used for which a high price can be supported.) If 101 is approved for NTM, would oral clofazimine be competition? It was approved in the US for leprosy as Lamprene, but was discontinued in 2004. It is also available for NTM under an expanded access program Once there is an FDA approved drug for NTM, I would think that patients would be prescribed the approved drug (MNKD-101), rather than doctors putting in a SPIND request. It is still approved, it's just that nobody sells it. If 101 turned out to be a success then Novartis may consider turning in the results from their expanded access trial and get Lamprene approved for NTM. They could just start selling it again and doctors could prescribe it off-label, but I suspect they would wait for approval. |
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Post by prcgorman2 on May 23, 2024 13:52:35 GMT -5
I assume 8/1/26 is on the paperwork, but I also thought MC said during the most recent EC, initial readout could be Q1 2025 (because they’re supposed to begin enrolling patients in June) and that it is possible 100% enrollment would be achieved by the time of the readout. (Would love to have that confirmed without having to listen to the EC again). I think the treatment lasts about 6 months. So maybe mid-2026 for FDA approval (if they use all of their permitted “Fast Track” 6 months). I’m not very knowledgeable of the process and timelines so caveat emptor. The initial readout is to decide it the trial can continue and is usually around the halfway mark. They are looking to see if there is a significant number of problems with the protocol and if they need to restart. Results from the read out are considered interesting, but not significant as only part of the cohort will have completed the trial (the bad outcomes may all be lurking in the second half). Good color. Thank you agedhippie. I think you're confirming that if the halfway mark is about 7 to 9 months from now, then the trial could be completed in 2025 assuming 100% enrollment is by the halfway mark. Yes? |
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Post by cjm18 on May 23, 2024 14:14:46 GMT -5
Best case for approval is 6 months (shorter review period) after Estimated Primary Completion Date of August 1, 2026? I assume 8/1/26 is on the paperwork, but I also thought MC said during the most recent EC, initial readout could be Q1 2025 (because they’re supposed to begin enrolling patients in June) and that it is possible 100% enrollment would be achieved by the time of the readout. (Would love to have that confirmed without having to listen to the EC again). I think the treatment lasts about 6 months. So maybe mid-2026 for FDA approval (if they use all of their permitted “Fast Track” 6 months). I’m not very knowledgeable of the process and timelines so caveat emptor. 100% enrollment by 1Q2025 + 6 months for late enrollees trial + 6 months for fast track review. = 1Q2026 approval. |
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Post by Clement on May 23, 2024 15:26:35 GMT -5
"Find out if ARIKAYCE is right for you On treatment but still testing positive for MAC? FDA Approved MAC (Mycobacterium avium complex) can be hard to treat. If you are still testing positive for MAC, you are not alone. For 1 in 3 people, a multidrug treatment alone may not be enough to test MAC-negative. That’s where ARIKAYCE comes in. Learn about adding the first and only FDA-approved treatment used in combination with multidrug therapy for adults who still test positive for MAC after at least 6 months on multidrug treatment alone. ARIKAYCE was approved by FDA using the Limited Population pathway. This means FDA has approved this drug for a limited and specific patient population, and studies on the drug may have only answered focused questions about its safety and effectiveness." www.arikayce.com/is-arikayce-right-for-you/ |
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Post by agedhippie on May 23, 2024 15:59:45 GMT -5
The initial readout is to decide it the trial can continue and is usually around the halfway mark. They are looking to see if there is a significant number of problems with the protocol and if they need to restart. Results from the read out are considered interesting, but not significant as only part of the cohort will have completed the trial (the bad outcomes may all be lurking in the second half). Good color. Thank you agedhippie. I think you're confirming that if the halfway mark is about 7 to 9 months from now, then the trial could be completed in 2025 assuming 100% enrollment is by the halfway mark. Yes? Mannkind say that the Primary Completion date is 2026-08-01 based on their filing. Expect six months beyond that for QC. There is a second date out in 2028 which I suspect covers the extended trial. |
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Post by agedhippie on May 23, 2024 16:05:58 GMT -5
"Find out if ARIKAYCE is right for you On treatment but still testing positive for MAC? FDA Approved MAC (Mycobacterium avium complex) can be hard to treat. If you are still testing positive for MAC, you are not alone. For 1 in 3 people, a multidrug treatment alone may not be enough to test MAC-negative. That’s where ARIKAYCE comes in. Learn about adding the first and only FDA-approved treatment used in combination with multidrug therapy for adults who still test positive for MAC after at least 6 months on multidrug treatment alone. ARIKAYCE was approved by FDA using the Limited Population pathway. This means FDA has approved this drug for a limited and specific patient population, and studies on the drug may have only answered focused questions about its safety and effectiveness." www.arikayce.com/is-arikayce-right-for-you/That is what I meant by payers requiring a step therapy. The multidrug treatment could work and the payer wants the cheapest viable option first. |
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Post by celo on May 23, 2024 16:30:03 GMT -5
Curious what role the current SAE's being mentioned by Mike are included with the oral versions? Was it 101 that was once used for leprosy and has many reported side affects? Mike feels with the new intervention lasting only six months, this reduces the systemic tox levels and thus, he expects more patient levels of compliance? If so, who will champion 101 as better than orals? MNKD? Clofazimine is already a treatment for NTM, just not a favored one as it is off-label. There are established antibiotics that are currently the first line drugs, but as the NTM variants become drug resistant they are less effective. The idea is that clofazimine is a newer line of attack that will encounter less drug resistance but at the price point that is being talked about I can see payers wanting it to be a step therapy. The issue for 101 is going to be that if MNKD establishes clofazimine as a viable option then the oral version of clofazimine will be considered again and that will create price pressure. There are also trials ongoing for new oral drugs like omadacycline although their timeline is beyond 101. Oral Clofazamine has toxic side effects due to the amount administered to have a positive effect. The goal for 101 is to lower dosage and remove most of the toxic side effects and possibly increase clofazamine benefits by only administering directly to the lungs. How will the old form be a competitor? If I have an oral with crappy side effects and a reduced benefit but is cheep, so what? That would be one inept doctor. |
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Post by agedhippie on May 23, 2024 22:31:29 GMT -5
Oral Clofazamine has toxic side effects due to the amount administered to have a positive effect. The goal for 101 is to lower dosage and remove most of the toxic side effects and possibly increase clofazamine benefits by only administering directly to the lungs. How will the old form be a competitor? If I have an oral with crappy side effects and a reduced benefit but is cheep, so what? That would be one inept doctor. It's not always down to the doctor or VDEX would always be able to prescribe Afrezza. It's often down to the payer, and especially for very expensive drugs. I don't see it as a huge problem since the probable progression would be multidrug -> oral Clofazamine -> 101. The initial multidrug step is likely to be a few months so the timescale is largely unaltered by the extra step as I expect the oral step would fail fast and they would move on to MNKD-101. Until there is an approved oral Clofazamine for NTM (Lamprene is not approved for NTM) the path would have to be multidrug -> MNKD-101 since an insurer cannot specify an off-label drug. |
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Post by ktim on May 24, 2024 17:54:33 GMT -5
Oral Clofazamine has toxic side effects due to the amount administered to have a positive effect. The goal for 101 is to lower dosage and remove most of the toxic side effects and possibly increase clofazamine benefits by only administering directly to the lungs. How will the old form be a competitor? If I have an oral with crappy side effects and a reduced benefit but is cheep, so what? That would be one inept doctor. It's not always down to the doctor or VDEX would always be able to prescribe Afrezza. It's often down to the payer, and especially for very expensive drugs. I don't see it as a huge problem since the probable progression would be multidrug -> oral Clofazamine -> 101. The initial multidrug step is likely to be a few months so the timescale is largely unaltered by the extra step as I expect the oral step would fail fast and they would move on to MNKD-101. Until there is an approved oral Clofazamine for NTM (Lamprene is not approved for NTM) the path would have to be multidrug -> MNKD-101 since an insurer cannot specify an off-label drug. Wouldn't oral use of Clofazimine that "fails" (doesn't cure) run the risk of developing resistance to Clofazimine? Seems if inhaled Clofazimine proves to be able to totally clear the infection, it should be step 2 after non-clofazimine multi-drug. |
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Post by letitride on May 24, 2024 18:43:31 GMT -5
Mannkind received orphan drug designation with a fast track because current treatments are anything but stellar. Assuming resistance to the adoption of MNKD 101 seems a bit senseless prior to trial results in my opinion.
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Post by agedhippie on May 24, 2024 23:07:08 GMT -5
It's not always down to the doctor or VDEX would always be able to prescribe Afrezza. It's often down to the payer, and especially for very expensive drugs. I don't see it as a huge problem since the probable progression would be multidrug -> oral Clofazamine -> 101. The initial multidrug step is likely to be a few months so the timescale is largely unaltered by the extra step as I expect the oral step would fail fast and they would move on to MNKD-101. Until there is an approved oral Clofazamine for NTM (Lamprene is not approved for NTM) the path would have to be multidrug -> MNKD-101 since an insurer cannot specify an off-label drug. Wouldn't oral use of Clofazimine that "fails" (doesn't cure) run the risk of developing resistance to Clofazimine? Seems if inhaled Clofazimine proves to be able to totally clear the infection, it should be step 2 after non-clofazimine multi-drug. Yes, I would expect it to be the step after multidrug. The insurer cannot specify an off-label drug so they cannot specify oral Clofazimine currently. I am not sure if inhaled Clofazimine has been studied in humans. All the work seems to have been in animals with this trial as a joint phase 2 and 3. That implies a phase 1 somewhere but I cannot find it and it is not listed in the clinical trials site. |
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Post by prcgorman2 on May 25, 2024 7:47:53 GMT -5
Wouldn't oral use of Clofazimine that "fails" (doesn't cure) run the risk of developing resistance to Clofazimine? Seems if inhaled Clofazimine proves to be able to totally clear the infection, it should be step 2 after non-clofazimine multi-drug. Yes, I would expect it to be the step after multidrug. The insurer cannot specify an off-label drug so they cannot specify oral Clofazimine currently. I am not sure if inhaled Clofazimine has been studied in humans. All the work seems to have been in animals with this trial as a joint phase 2 and 3. That implies a phase 1 somewhere but I cannot find it and it is not listed in the clinical trials site. Been here how many years? And still learning. It never occurred to me to understand the relationship between animal testing and human trials. If I remember correctly, MC made comments in the last earnings call about animal testing to guage efficacy and toxicity. I think he was talking about clofazimine and not nintedanib but I’d have to go back and listen (again) to be sure. |
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