Radiopharmaceutical companies are primed for increased investor interest as the sector is seeing meaningful progress that is currently being overlooked in favor of ADCs. Tailwinds are underway that will validate and position radiopharmaceuticals as promising treatments for solid tumors. This rising tide could lift all companies in the space as investors begin to realize that current hurdles are things of the past.
Radiopharmaceuticals Resemblance to ADCs
Radiopharmaceuticals use a radioactive compound combined with a targeting molecule via a linker. Once in the body, the targeting molecule (PSMA, FAP, HER2 etc. antibodies) can deliver the radioactive compound to the cancer cells. It is a similar approach to antibody-drug conjugates (ADC), that has seen a recent surge of interest (read details here).
Radiopharmaceutical treatments retain the advantages of radiotherapy’s ability to kill cancer cells, but are able to deliver the therapy in a more targeted manner. Just as ADCs combine chemo-like payloads with targeting antibodies. The difference between the two is that the toxic payloads of ADCs need to be absorbed into cancer cells, whereas radiopharmaceuticals can still do damage even when only bound to the cancer.
Why Now? Radiopharmaceuticals Are Overcoming Past Hurdles
Moving Beyond Prostate Cancer
In March 2022, the FDA approved the first radiopharmaceutical for prostate cancer – Novartis’ Pluvicto. There is now an increased applicability for using this approach. Ongoing studies in multiple indications are using a combination of different radioactive compounds and targets.
Novartis’ Radiopharmaceutical Launch Showing Demand > Supply
Just a year after approval, Novartis’ Pluvicto generated $211M in Q1 2023 sales. According to Novartis, demand is continuing to exceed supply. For the full year 2023, Novartis mentioned that Pluvicto will exceed $1B in sales. Pluvicto is moving in earlier lines of prostate cancer treatment which will further amplify its position as a blockbuster for Novartis.
Similarly, Lutathera, which was approved in 2018, generated $149M in Q1 2023 and on pace to being a $600M drug. Novartis is also running trials to move Lutathera in earlier lines of GEP-NET treatment and other solid tumors.
All in all, Novartis’ enthusiasm and exceeding expectations demonstrates there is clear demand for radiopharmaceuticals treatments.
Supply Chain Issues Getting Resolved
Supply problems have burdened Novartis’ Pluvicto and Lutathera, with supply constraints limiting existing patient doses and also delaying treatment for potential new takers. Such supply problems have persisted largely because radiopharmaceuticals are an immature, non-commoditized business that lacks back-up production capacity. As a result of few approved radiopharmaceuticals, there are not many manufacturing companies tackling the issue.
With Novartis’ commitment to the space, and others like Lantheus and Telix also nearing commercialization for their therapeutic programs, this supply constraint is expected to be an issue of the past. Novartis has already ramped up supply in 2 facilities and is expecting to have capacity of 250K doses annually for 2024 and onward.
Upcoming Catalysts to Draw Investor Interest
1. Point/Lantheus Topline Data 2H 2023
PNT2002, the 177-LU + PSMA targeting agent in mCRPC, is set to report Phase 3 topline data during 2H 2023. Point Biopharma (PNT) handed PNT2002 over to Lantheus (LNTH) in exchange for $260M upfront, $280M on approval, up to $1.55B in milestones and a 20% royalty. As part of the agreement, Point will fund and complete the phase 3, following which Lantheus will file the NDA and commercialize the drug due to their extensive diagnostic distribution in the radiopharmaceutical space.
Expectations for PNT2002’s Phase 3:
- Median radiographic progression free survival (rPFS) of at least 11.5months
- At least 40% of patients with PSA declines by 50% or more.
- OS of at least 15 months
With Lantheus controlling the upcoming NDA filing and commercial activity of PNT2002, it seems that Novartis will have competition in the mCRPC space within 18 months.
2. Actinium Data Over Next 12 Months
Johnson & Johnson (JNJ), Fusion (FUSN) & Actinium (ATNM) use actinium-225 as their radioactive compound, rather than lutetium-177 like other advanced players Novartis, Lantheus, Telix and Point. Although actinium is not as short-lived as lutetium, due to a longer half-life, it is more precise, so it reaches fewer nearby cells around the targeted cancer. This is anticipated to lead to fewer side effects.
Over the coming 12 months, there will be several actinium updates that will give an early look at efficacy of the radioactive compound:
- First Look at JNJ-69086420 Data
Johnson & Johnson is running a Phase 1 study in mCRPC patients. JNJ-69086420 is a first-in-class actinium radioimmunotherapy targeted to hK2 , which is an antigen expressed in prostate cancers and minimally expressed in normal non-prostate tissue. The trial began enrollment in December 2020 and, as of May 15 2022, had 73 patients enrolled. Although no guidance has been shared, we anticipate an update might be given at ASCO GU in January 2024.
- Fusion’s IFG-1R & PSMA Targets
Fusion reported an update on their IGF-1R targeting radiopharmaceutical, FPI-1434, Phase 1 trial at the SNMMI Annual Meeting on June 27, 2023. In low dose cold/hot (15 kBq/kg) cohort, Fusion demonstrated an improved safety profile but stable disease as best response. The company will need better efficacy to be viable, so the hope is that higher dosed cohort 2 or 3 are able to report responses. FPI-1434 is currently dosing cohort 2 (25 kBq/kg) in cold/hot regimen (equivalent to 75 kBq/kg in the hot only study). Data on this cohort is expected by year end 2023.
The more important catalyst for Fusion is data from 225Ac-PSMA in mCRPC patients. This data is expected 1H 2024 and will report on 20-30 patients, including safety and efficacy where PSA50 responses should be between 40-60%.
- ATNM’s CD33 targeting radiotherapeutic
ATNM’s actimab-A uses a CD33 targeting antibody and actinium 225 as the radioactive agent to target acute myeloid leukemia (AML). In combination with chemo regimen CLAG-M, actimab-A demonstrated a 67% ORR and 12-month median OS. ATNM will give an update on strategy to move this therapy into pivotal trials in 2H 2023.
ATNM will also report proof of concept Phase 1/2 that is combining their actimab-A + venetoclax, a small molecule Bcl-2 inhibitor, for patients with AML. Actimab-A + venetoclax combination has been well tolerated with responses, including a CR and a partial response in early dose escalation cohorts. Proof of concept data is expected 2H 2023 and should demonstrate complete response rates of at least 50%.
3. Tracking Novartis’ Launch Progress & Supply Chain Developments
Novartis’ leadership position in radiopharmaceuticals makes it the de facto industry anchor. Therefore, the sales progress of Pluvicto & Lutathera will be lead indicators of interest for radiopharmaceuticals. This puts importance on NVS earnings as industry wide catalysts.
PropThink contributors hold no positions in any of the names mentioned
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