As reported in Seeking Alpha, Sales of both Revlimid and Darzalex are growing, but Darzalex is growing faster, particularly outside the US. Darzalex has gained favor with experts because of its myeloma specificity, positive phase 3 trial results, and safety profile. Indirect comparisons show survival advantage of Darzalex-based over Revlimid-based regimens. Treatment guidelines embrace a plethora of regimens, and there is a need to start from scratch with a targeted therapy like Darzalex upon which a few regimens can be based. There is even some interest in trials of Darzalex as monotherapy supported by retrospective analyses in Europe, and a recent trial registration by NCI.As populations age and   myeloma becomes more prevalent, sales of Celgene’s (CELG) Revlimid and Johnson & Johnson’s (JNJ) Darzalex are both growing, but Darzalex is growing faster. The growth of Darzalex relative to that of Revlimid is even faster outside than in the US.

Left panel below shows US sales since 2016Q2 for Darzalex (left axis, $298m in 2018Q2) vs Revlimid (right axis, $1,586m in 2018Q2). Right panel shows non-US sales, same axes.

Source: authors own data using sec filings.

There are reasons for the US vs non-US growth anomaly, and reason to believe that the relative outperformance of Darzalex will continue. Myeloma treatment guidelines are a mess. There a myriad of regimens preferred by or acceptable to the NCCN (National Comprehensive Cancer Network), and they differ depending on whether the patients are either stem cell transplant candidates, non-transplant candidates, or previously treated (often relapsed/refractory). Lacking clear guidelines leaves an unmet need for an evidence-based, cost-effective, tolerable regimen based on a myeloma-targeting drug. There are now 3 well-studied myeloma cell surface targets, one of which is CD38 against which Darzalex is designed (the other targets are slamF7 and BCMA). Darzalex is currently the most advanced of novel therapies that specifically attack one of these surface targets.

Groundwork has been laid by several phase 3 trials that have shown the benefit of adding Darzalex to Revlimid-based or Revlimid-free combinations for myeloma. Most trials like POLLUX and CASTOR have enrolled patients that have become refractory to all drugs and combinations of drugs which speaks to the so-far incurable nature of this disease. ALCYONE (Mateo et al., NEJM 2018) enrolled 706 newly diagnosed, previously untreated patients with myeloma, mostly from Europe. Median progression-free survival was lengthened to >27 months by adding Darzalex to a Revlimid-free combo (PFS = 18 months), and compared favorably to the PFS of 20.7 months with Revlimid plus dexamethasone in FIRST (Benbaubker et al. NEJM 2014).

In a Janssen-sponsored analysis (Van Sanden et al. Oncologist 2018) of myeloma patients from 4 different trials, overall survival with Darzalex alone was superior to treatment with Celgene’s Pomalyst plus low-dose dexamethasone. In the absence of published head-to-head comparisons of Darzalex-based with Revlimid-based regimens, the guidelines will remain cluttered with numerous options. Starting from scratch. The National Cancer Institute and MD Anderson have recently registered a phase 2 trial that will examine the rate of complete remission and PFS with Darzalex alone following salvage (ie patients have failed drug therapies) autologous stem cell transplantation. This is the most recently registered trial among 28 for myeloma post-transplant in which NCI is collaborator or sponsor, and the only single drug study among those.

Experts at NCI and elsewhere recognize Darzalex as “a singular breakthrough in the treatment of myeloma” (Rajkumar & Kyle, 2016). Darzalex has greater clinical benefit than Revlimid in indirect comparisons. There is interest in its use as monotherapy. These are all catalysts for Darzalex sales which will likely continue to grow faster than sales of Revlimid.

Among the NCCN’s preferred, other recommended, and sometimes useful regimens, there are 19 different drugs listed below according to mechanism of action. Regimens of 2-3 drugs are often described as being based on one of them (eg “lenalidomide-based” or “immunomodulator-based”:

Immunomodulators: lenalidomide (Revlimid), pomalidomide (Pomalyst), thalidomide

Proteasome inhibitors: bortezomib, carfilzomib, ixazomib

Corticosteroids: dexamethasone, prednisone

Targeted against CD38: daratumumab

Targeted against SLAMf7: elotuzumab

Chemotherapy: bendamustine, cisplatin, cyclophosphamide, doxorubicin, etoposide, melphalan, vincristine

Histone-deacetylase inhibitors: panobinostat

Revlimid is well-entrenched in clinical practice, and is part of preferred and “category 1” primary therapy regimens, whether the patient is a transplant candidate or not, and included in regimens for those previously treated.

However, Revlimid is a chemical, not a biological, has a multitude of effects, not a precisely targeted effect. In the current era of biotechnology, it is hard to believe that there will not be a move away from the former towards the latter.

That shift has already started in Europe. ALCYONE was European with Spain in the lead. The Van Sanden group cited above is European. Europeans are much more cost conscious than we have been in the US, and narrowing the number of recommended regimens to include the fewest but most effective drugs will be cost-effective.

Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.

I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.


Source: Seeking Alpha

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