For biopharma investors, the push for legislation to beef up FDA’s authority over pharmacycompounding boils down to just two products: Avastin and Makena. So why is no one talking about them on Capitol Hill?
The Senate is moving forward with legislation to beef up FDA’s authority over pharmacy compounding in response to the meningitis outbreak associated with products shipped by a Massachusetts compounder.
For biopharma investors, that authority matters for exactly two products: Avastin and Makena.
The former is widely repacked in microdoses for ophthalmic use, cutting into the market for Roche/Genentech’s Lucentis and Regeneron’s Eylea. The latter is KV Pharma’s brand of the pre-term labor therapy hydroxyprogesterone, which is still so widely used in compounded versions that the company is in bankruptcy .
The legislation doesn’t mention either drug by name – and the legislators aren’t mentioning them either.
The former omission is to be expected: the bill covers all compounding activities, and the authorities are framed generally, not specifically.
The latter omission is more interesting as a study in the value of short-term memory loss as a survival skill for politicians. After all, the only reason the two products are so widely compounded is, frankly, thanks to the Senate.
In the case of Avastin, the initial off-label use of the therapy was driven by ophthalmologists who saw the anti-VEGF therapy as a true breakthrough in treating macular degeneration, and didn’t want to wait for Genentech to finish development of the related (and, as it turned out, vastly more expensive) product Lucentis. Thanks largely to the efforts of former Senate Aging Committee Chairman Herb Kohl (D-Wisconsin), the off-label use has been permitted to continue—and has even been encouraged by federally funded research conducted by the National Institutes of Health.
Makena compounding was also protected by Senatorial fiat, in this case primarily by Sen. Sherrod Brown (D-Ohio), who emphasized to both FDA and the Centers for Medicare & Medicaid Services that he felt that KV’s price was exorbitant and that compounders should be allowed to continue providing alternatives.
Left to its own devices, FDA would likely have clamped down on both long ago—albeit for different reasons that perfectly illustrate the two very different ways that high volume compounding challenges the FDA regulatory model.
For intraocular Avastin, the issue is safety – the core of FDA’s mission since it was founded a century ago. From the agency’s standpoint, intraocular injections are the single highest risk category of medication, and so the idea of mass repackaging of Avastin is troubling
For Makena, the issue is the integrity of the approval process. If mass compounding of 17P is permitted despite the launch of an FDA approved product, why would any sponsor ever go to the time and bother of FDA approval in the future? Bear in mind in particular that the Makena approval carried an accelerated approval requirement for KV to study its actual impact on the health of newborns (beyond the simple delay in delivery date). Without an approved product, the core question of clinical benefit would never be answered.
The Senate legislation would more clearly deal with Makena than with Avastin: the draft bill would prohibit high-volume compounding of copies of FDA approved drugs except in the case of shortages. While there may still be room to argue about what is or is not a “copy” of Makena, enactment of that language would likely significantly curtail if not completely eliminate compounding of that product.
In the case of Avastin, the bill would explicitly define repackaging of sterile products as “compound manufacturing” and therefore bring it under the new regulatory regime.
However, it would not explicitly direct FDA to stop the practice. Instead, FDA would have the authority to create a “do-not-compound” list of products that should not be produced by “compounding manufacturers,” and would clearly have the authority to put Avastin on that list.
Of course, FDA probably already has the authority to shut down high-volume Avastin repackagers, and it certainly has the ability to make their lives more difficult even if its authorities don’t extend that far.
But that takes us back to where we began: FDA’s handling of Avastin compounders has never been an issue of its own authorities and its own assessment of the risks. It has been a political issue, tied to the vast price disparity between the approved products and the compounds.
That dynamic won’t change just because the Senate passes new legislation.
Indeed, the most recent hearing on compounding in the Senate included the first references toMakena in the context of the response to meningitis outbreak. It came from Sen. Tammy Baldwin, the Democrat who won Kohl’s senate seat in Wisconsin. She asked Center for Drug Evaluation & Research Director Janet Woodcock whether FDA would let itself be “manipulated” by firms seeking “competitive advantage” in determining what would or would not be on the “do not compound” list.
In addition, Baldwin suggested concern that the prohibition on compounding FDA approved drugs would have a negative impact on “access.” She noted how dramatically more expensive Makenawas than the compounded versions used before it was approved.
Woodcock responded by stressing that FDA doesn’t usually “balance human safety concerns against economic considerations.”
That sounds like a job for the United States Senate.
No comments:
Post a Comment