(1) Update on Novartis Pluvicto shortage . . . and (2) FDA’s (sNDA) for Illuccix to help with it.

[cujoe]

(1) Here is a update via MedPage Today on the shortage of Novartis' Plucvicto LU-177 drug and the sNDA for Illuccix. The following statement from Novartis summarizes the current situation and projections for the next year:

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Novartis Pharmaceuticals Corporation

1 Health Plaza, East Hanover, NJ 07936, Telephone [phone]

Novartis Update for Patients on Supply of PluvictoTM

Following recent delivery challenges for Pluvicto™, we understand you and your loved ones may have questions about the supply situation and the impact it may have on the treatment plans you made with your health care team. We recognize rescheduling doses may cause difficulties and uncertainties for you, and we are taking steps to enhance our supply reliability. While some of ourefforts will make a difference over time, in the short term we are also taking key actions to address potential rescheduling of doses.

Background on Supply Challenges:

• Pluvicto is currently made in our manufacturing facility in Italy in small batches, with only a five-day window for each dose to reach its intended patient. Any interruption in the process – either caused by unplanned manufacturing events, weather-related shipping delays or the challenges associated with importing a nuclear medicine into the U.S. – can result in doses not arriving in time. When that happens, impacted doses must be rescheduled and remade, causing the need to also reschedule other patient doses behind them.

• We are operating our production site at full capacity to treat as many patients as possible, as quickly as possible. However, with a nuclear medicine like Pluvicto, there is no\ back-up supply that we can draw from when we experience a delay.

• We are working to increase production capacity and supply of Pluvicto over the next 12 months with two new manufacturing sites in the U.S. While this will make a difference over time, we will be adjusting our approach to supply in the short term.

Our Near-Term Approach to Supply:

• Our priority is to supply those patients who have received their first doses and are currently in the treatment process. This is important to allow patients who have already begun the treatment cycle to appropriately complete their course of therapy.

• As we endeavor to provide patients who have received one or more doses with their full treatment course, patients who are currently in our scheduling system and awaiting their first doses will need to be rescheduled. We will be reaching out to your health care provider with options for rescheduling. We are striving to serve as many patients as possible as quickly as possible as we work through the current situation.

• In the same spirit, we will not be able to take any new orders until we have clarity on the FDA’s approval of one of our new sites (expected within the next four to six months). We are working quickly to address these challenges as soon as possible. In the meantime, we are committed to continuing these updates as we work to meet the high demand for this medicine, so you and your health care providers can make the best treatment decision.\

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FAQS

How long do you anticipate these supply challenges will last?

We are making investments to increase our production capacity, and we aim to significantly increase Pluvicto supply over the next 12 months with two new manufacturing sites in the U.S.

I haven’t received a first dose yet, when will I be able to start my treatment?

Patients who are currently in our scheduling system and awaiting their first doses will need to be rescheduled. We will be reaching out to your health care provider with options for rescheduling.

Why hasn’t Novartis produced a mass amount of Pluvicto to store for situations like these?

As a nuclear medicine, Pluvicto is made in small batches with only a five-day window for each dose to reach its intended patient. Therefore, there is no back-up supply that we can draw from when we experience a delay.

Will Novartis cover travel expenses for rescheduled doses?

Please call 1-844-638-7222 with any questions related to travel impact due to dose rescheduling.

Who can I talk to at Novartis for more information?

Please call 1-888-NOW-NOVA (1-888-669-6682) to speak with a Novartis representative.

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(2) Due to the Pluvicto shortage, the FDA “has approved a supplementary New Drug Application (sNDA) for Illuccix® (kit for the preparation of gallium Ga 68 gozetotide injection) to enable its use for the selection of patients with metastatic prostate cancer, for whom 177Lu 177 PSMA-directed therapy is indicated."

I’m not familiar with the equivalency of Illuccix to Pluvicto, but it is good the FDA is providing an immediate option for patients in critical need of PSMA-directed treatment. Here is a link to the press release from Telix Pharamceuticals about the approval:

FDA Approves Expanded Indication for Telix's Illuccix® to Include Patient Selection for PSMA-Directed Radioligand Therapy, Telex Pharamceuticals Limited, Mar 16, 2023, 08:28 ET

prnewswire.com/news-release...

Keep it S &W, Ciao - K9

[NPfisherman]

Dog of Terror,

I see the Illuccix making the shortage possibly more pronounced... increased demand...The Lu-177 and AC-225 radioligand treatments have changed the course of disease treatment... The ability to ID patients that can most benefit from treatment, or not, is part of the evolving precision medicine... "The times, they are a changin'..."... and Bob wasn't lyin'...

DD

[noahware in reply to NPfisherman]

I wonder: will the ability to ID patients that can most benefit from Lu177 treatment really be pursued to the fullest possible extent with regard to which men get Pluvicto in the US? If that was the case, I would think giving men FDG scans (to check for potential discordance) would be the rule, rather than the exception (as seems to be the case).

Certainly any man who has exhausted other treatments should be able to pursue this one. But the mere fact of having exhausted other treatments does not make one a better (or worse) candidate for a successful Pluvicto outcome. Are the factors that probably DO make one a better (or worse) candidate being carefully considered when US doctors mention Pluvicto to their patients?

I think the Germans, Australians and other who have been using Lu177 for some time have a better handle on which men are most likely to benefit from it and which are least likely. In the event of shortages, it makes sense to give preference to the former group over the latter, but I'm not sure how well that would go over in the US system... I think it would be seen as "denying treatment" to men who MIGHT benefit.

[NPfisherman in reply to noahware]

Good questions. I will be asking about an FDG scan next week at my f/u appt. While I am not a candidate for Pluvicto, I do believe getting f/u scans with FDG and Pylarify should be part of the treatment plan, so no one gets caught unaware... PCA is a sneaky disease... I have not had an FDG scan yet, so not sure how my MO will react...

Fish

[marnieg46 in reply to NPfisherman]

G'day Dave.

I know for the lutetium trials that I have followed conducted at Peter Mac they have insisted on an FDG to ensure that those who are selected are going to gain the most benefits. From memory I seem to recall that Sartor said in one of the UroToday videos that the Vision Trial didn't require a FDG but Michael Hoffman always defends the decision taken to rule out those with a response on a FDG. At least that's the case for trials.

In other situations, as it's also offered at PM on compassionate grounds given it's not funded in Australia as yet, I would suspect that the advice would be that no real benefits will be obtained for those who are responsive on an FDG.

I did try to search for Michael's explanation about the rationale for eliminating those who have a FDG response to reply to noahware but it's within a podcast and the night was slipping away...

Trust all goes well for you as it does here...😊 Marnie

[NPfisherman in reply to marnieg46]

Hi Marnie,

The FDG scan for finding non PSMA tumors to indicate less likely to respond to Lu 177 makes sense to find the most likely to respond . For those who have had a low PSA for most of their treatment history, an FDG scan to verify that nothing more is going on is reassuring . Hope all things are going well in Oz...

Dave

[cujoe in reply to noahware]

It seems in the US system, all new treatments (without a long history of use) start with the most heavily treated and least risk-averse patient communities. That may make sense to the portions of our medical system that are most exposed to liablity issues related to new "less proven" treatments, but it is obvious to many of us in the patient community that PSMA directed treatment would most likely be more effective when used early - before cancer mutations have developed that are not PSA avid.

While not yet fully tested, the same might well be the case for BAT as a treatment strategy for hsPCa. Thus, we see many n=1 non-SOC/modified- SOC treatment programs utilizing both PSMA theranostics (at off-shore centers) and hsBAT being used effectively by members here at FPC. I'd quote Mukherjee's 2nd Law again, but people are probably getting tired of me doing that.

Ciao - Capt'n K9

[NPfisherman in reply to cujoe]

K9 Terror,

Normals make the rules, and outliers make the law.. I think the treatment mileu is changing faster based on developments, even before Phase 3 studies occur. My own case is an example...IADT treatment for only one year... When did that study occur?? It didn't... and I am not the only person on these forums doing that plan... I think it works for slowing resistance...

Are MOs keeping track of n=1 experiments, grouping them together, and adjusting. My MO has a group of oligos that he and the other MO at Cleveland Clinic are tracking for results based on tx. Not a study, but could be...The plot thickens....

DD

[cujoe in reply to NPfisherman]

I hope you are right about the tracking of patient outliers as 'informants" for mods to existing or completely new treatment protocols. Mayo Clinic is the only cancer center that I am aware of that frequently provides n=1 (individual or cumulative) patient outcomes in well-documented papers. And while, I'm truly sorry for the patients in NOLA who are losing Dr. Sartor to Mayo MN, I expect his broadminded willingness to embrace and even push new treatment protocols makes him a perfect fit there. (He may, however, find the weather there much less kind and the nightlife less robust.)

As for IADT, that was my original agreed-upon treatment plan. However, through the purely chance occurrence you are already familiar with, I did just one 3-mo lupron injection, had a perfect response and went on to remain <0.1 undetectable for about four years. I even reached a new post-surgery nadir of 0.02 towards the end of that treatment vacation.

With BCR #2 in mid-2021, I am now doing a CONSIDERABLY less structured IADT program than you. Being a surprised recipient of the bicalutamide booby prize has recently interrupted my self-directed treatment plan going into my MO appt early next month, so I will need to reevaluate based on labs at that appt. Fortunately, the tamoxifen is doing its job, so I may be able to restart the bicalutamide without waiting for prophylactic RT. Next labs will show how effective dutasteride + tamoxifen is for my flavor of PCa.

You are obviously in good hands and adjusting your treatment intervals to regain that all important QOL that ADT tries to take away for us. Good luck with next labs and the potential for another treatment vacation. Your active life around the property and with the Victorian Project are helping to preserve QOL until you get that next vacation. Keep it up and Stay S & W while you do. Ciao - Capt'n K9

[NPfisherman in reply to cujoe]

Dog of Terror,

Hoping the dutasteride and tamoxifen get it done for you, and the lab work is good..

All the best,

DD

[cujoe in reply to NPfisherman]

Thanx, Brother Dave/Don/NP/DD

[NPfisherman in reply to cujoe]

Dog of Terror,

Some days, I do not know who I am... maybe it's the ADT and Abi... or the multiple roles... Who knows??

DD

[cujoe in reply to NPfisherman]

You post and comment and we'll figure out.