If you are truly interested in why Prolia sales are somewhat low, from the perspective of an MD who specializes in osteoporosis -
I think it is a good drug for oncology (e.g., H of M, MBD, etc., and patients with tumors with a prediliction for bone, such as myeloma, prostate and breast cancer). However, currently, for osteoporosis, I'm reserving it for patients who are not appropriate candidates for Reclast, for the following reasons:
1. While the fracture efficacy data are terrific, they are no better than the data for Reclast, but there are several areas of potential concern:
a. 60 mg q 6 months appears to reduce the rate of bone turnover somewhat more than is optimal. Alendronate 10 mg/day or 70 mg/month, ibandronate 150 mg/month, and zoledronic acid 4-5 mg per year (or every 2 years) all reduce the rate of bone turnover by 50-70%, which reduces BT into the pre-menopausal normal range. Which is pretty comparable to the BT effect of full dose ERT. The effect of DMAB 60 mg q 6 months on BT is sgnificantly greater than these agents. While normalizing BT appears to result in improved bone strength, it is at least possible that reducing BT to a greater extent may not be optimal.
b. In this regard, as a bone expert, it is somewhat concerning that about 35% of the patients in the FREEDOM bone biopsy cohort did not demonstrate any TCN label. Not no double label - NO label at all. This finding, which is c/w NO ongoing bone turnover/bone formation, has not been seen in any of the histomorphometry programs with Fosamax, Actonel, Boniva or Reclast.
c. Both ONJ and atypical femur fractures appear to be due, at least in part, to over-suppression of bone turnover. The incidence of ONJ in the DMAB oncology program controlled by Zometa was comparable to the incidence with Zometa (numericaly greater, but NS difference). There are no data from extensive controlled trials (N about 60,000 p-y) that bisphosphonates at osteoporosis doses increase the risk of atypical fractures, although it is possible that they might increase in the risk in a small number of susceptible patients. However, and I speak as a KOL (and I suspect most of my colleagues would agree), if BPs do effect the risk of atypical fractures, I would expect Prolia to be at least as risky, because it reduces BT to a significantly greater extent than oral or IV bisphosphonates.
d. As mentioned by some of your more knowledgable sales rep colleagues, the rebound increase in osteoclastic bone resorption seen after stopping Prolia is of some concern. If patients who d/c Prolia are not placed on a BP, I would definitely predict the possibility of an increased fracture rate, especially in patients with more severe osteoporosis, due to enhanced trabecular perforation. The rebound increase in BT is actually quite impressive, as is the rapid loss of the BMD gains following discontinuation.
So I'm using Prolia in a couple of patients with pretty severe renal failure, and a couple of the rare patients who appear to be idiosyncratically sensitive to BPs (e.g., severe muscle & joint pains with oral BPs). But in the great majority of patients with moderately severe to severe osteoporosis, the 1st line is alendronate. If there are GI tolerability issues, or compliance issues, or evidence of poor absorption, I change to Reclast. Think about it from the perspective of the prescribing physician - with no efficacy advantage over Reclast, but with some additional safety concerns, and a smaller safety database (which will improve with time, of course), why would I go with Prolia right away?
This is not the fault of the sales reps, it's based on the controlled trial data. As more safety data rolls out, there's definitely the possibility that I may prescribe it for more patients. But no one should have predicted that this would be a blockbuster (for osteoporosis - I'm not talking about oncology here) right out of the blocks. Which I know doesn't help you with your sales targets, which are probably unrealistic in the current safety-focused environment.
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