FDA Hears from Industry on Draft Biosimilars Guidances
Here’s an informative report on the May 11 hearing regarding the 3 draft guidances on biosimilars which was published in Genetic Engineering & Biotechnology News.
FDA Has Received 9 Biosimilar INDs
As of February 15, nine Investigational New Drug applications have been lodged with FDA for 351(k) biosimilars. That’s according to Rachel Sherman, the CDER Associate Director for Medical Policy, who presented the “Biosimilar Guidance Webinar” on that day. Sherman provided some further statistics:
- There have been 35 Pre-IND meeting requests for proposed biosimilar products to 11 reference products
- 21 Pre-IND sponsor meetings have been held to date
So it looks like a number of companies are testing the U.S. biosimilar waters. Given the lingering uncertainty over the requirements for approval, and the amount of data that has already been collected for some biosimilar products that have been approved in Europe, it is hard to guess when FDA will receive its first application for approval under 351(k).
Period for comment on Draft Biosimilars Guidance closed
Genetic Engineering & Biotechnology News published an interesting article summarizing some of the points found in comments submitted to FDA in response to its publication of the three draft guidances on biosimilar applications. All sorts of stakeholders from biological innovators (Genentech and Novo Nordisk) to patient groups to a biosimilar manufacturer (Biocon) leveled criticisms at the Guidances. We’ll see whether FDA takes any to heart in its final Guidances.
Will the BPCIA go down with Health Care Reform?
As the Supreme Court’s week of arguments on the constitutionality of the individual mandate provisions of the 2010 health care reform act progressed, the pundits have seemed more and more certain that the Court will find these provisions unconstitutional. But what does that mean for the rest of the Act, and from our perspective, does that mean anything for biosimilars?
The Biologics Price Competition Act (BPCIA) was enacted as part of the Patient Protection and Affordable Care Act, currently under the Supreme Court’s scrutiny. Theoretically, if the Supreme Court holds any aspect of the Act unconstitutional, it can strike it from the books in its entirety. Alternatively, the Court can sever the suspect provisions, and leave the rest of the Act intact. The Court devoted its session on Wednesday to this issue of severability.
The plaintiffs (>20 States and some individuals) argued that the entire Act should be struck down: “If the individual mandate is unconstitutional, then the rest of the Act cannot stand.” Paul Clement, 3/28/12 Transcript at 4. From their questions to counsel, it seems that most of the Justices believe the Court has the power to sever provisions of the Act. The debate was should they sever, and if so, how? As shown in the quotes below, at least a couple Justices seem to think it’s unwise or infeasible for the Court to pick and choose provisions of the Act to preserve.
Several of the Justices explicitly called out the biosimilar provisions as unrelated to the constitutionally suspect mandates for individuals to purchase health insurance. For example, J. Breyer identified the BPCIA, as well as some other provisions as being able to stand on their own:
I would say the Breast Feeding Act, the getting doctors to serve underserved areas, the biosimilar thing and drug regulation, the CLASS Act, those have nothing to do with the stuff that we’ve been talking about yesterday and the day before, okay? So if you ask me at that level, I would say, sure, they have nothing to do with it, they could stand on their own. The Indian thing about helping the underserved Native Americans, all that stuff has nothing to do. Black lung disease, nothing to do with it, okay? So that’s – do you know what you have there? A total off-the-cuff impression. So that’s why I am asking you, what should I do? Tr. at 23. See also Tr. at 14 (Ginsberg).
Nonetheless, two influential Justices, Scalia and Kennedy, at least seemed to be leaning against severing and preserving any provisions, which would lead to the demise of the BPCIA:
J. Scalia:
“My approach would say if you take the heart out of the statute, the statute’s gone. That enables Congress to – to do what it wants in – in the usual fashion. And it doesn’t inject us into the process of saying: This is good, this is bad, this is good, this is bad. It seems to me it reduces our options the most and increases Congress’s the most.” Tr. at 73. See also Tr. at 10, 35, 38.
J. Kennedy:
When you say judicial restraint, you are echoing the earlier premise that it increases the judicial power if the judiciary strikes down other provisions of the Act. I suggest to you it might be quite the opposite. We would be exercising the judicial power if one Act was – one provision was stricken and the others remained to impose a risk on insurance companies that Congress had never intended. By reason of this Court, we would have a new regime that Congress did not provide for, did not consider. That, it seems to me, can be argued at least to be a more extreme exercise of judicial power than to strike – than striking the whole. … I just don’t accept the premise. Tr. at 36.
Of course, two Justices do not make a majority, and it’s possible that even these Justices, particularly J. Kennedy, were focused on other provisions that directly relate to health care funding. And, severability only becomes an issue if the Court rules that the mandate provisions are unconstitutional. On the other hand, several other Justices, although apparently certain that the “peripheral” provisions should be severed, expressed concerns over the practicality of the Supreme Court pouring over the 2700-page Act to identify what’s appropriate to preserve. So, in a nutshell, there seems like there’s a small, but real chance that the entire act, including the BPCIA, will be struck down. That possibility would leave the stakeholders in the biosimilars space with either the exciting opportunity or the terrifying risk of Congress redesigning the BPCIA from the ground up. One thing is for sure — if the BPCIA is struck down, the long path to the first approval of a biosimilar will get much, much longer.
Supreme Court Remands Myriad Case in Light of Mayo v. Prometheus
Remember the Myriad case, where a number of Medical Associations and individual doctors — assisted by the American Civil Liberties Union and the Public Patent Foundation — sued Myriad for a declaration that Myriad’s BRCA diagnostic testing patents were invalid because they were directed to unpatentable subject matter under § 101 of the Patent Code? If not, see our July 29, 2011 post to refresh your recollection.
In Myriad, a panel of the Federal Circuit Court of Appeals held that Myriad’s isolated BRCA DNA claims patentable under § 101, but its method claims for analyzing patients for mutations in these genes unpatentable. Having just found Prometheus’s claims to a different type of diagnostic test unpatentable under § 101, the Supreme Court has now remanded the Myriad case, which had been subject of a pending writ of certiorari, back to the Federal Circuit with instructions to reconsider in light of Mayo v. Prometheus.
It will be very interesting to see whether the Federal Circuit panel chooses to interpret Prometheus v. Mayo broadly enough to reverse its decision that claims to isolated DNA sequences are patentable. Judge Lourie’s opinion in Myriad held that isolated DNA sequences are patentable because “BRCA1 and BRCA2 in their isolated state are not the same molecules as DNA as it exists in the body; human intervention in cleaving or synthesizing a portion of a native chromosomal DNA imparts on that isolated DNA a distinctive chemical identity from that possessed by native DNA.” Slip Op. at 42. This “distinctive chemical identity” test seems a slender reed now that the Supreme Court rejected the Federal Circuit’s holding in Mayo that the human interventions of “administering” a drug and “determining” its levels in the body conferred patentability to Prometheus’s claims.
FDA Response to Citizen Petition Confirms that the BPCIA is the Only Abbreviated Route for Drugs Previously Approved Via a BLA
FDA recently published its Response to a 2009 Citizen Petition from Therapeutic Proteins, Inc. which requested FDA “exercise its authority and make necessary amendments to its rules to allow submission of biological drug marketing authorization applications [including BLAs submitted under the PHS Act] under aNDA ….” In short, FDA concluded that there is no ANDA end-around to the recently enacted biosimilar approval pathway under the BPCIA:
The 505(b)(2) and 505(j) approval pathways are available only for products for which the listed drug relied upon or RLD, respectively, was approved under section 505(c) of the FD&C Act. Because the 505(j) pathway is not available for a proposed product that seeks to rely upon a biological product licensed under section 351(a) of the PHS Act, your Petition is denied in part. The BPCI Act was enacted after the submission of your Petition. A sponsor seeking to submit an abbreviated marketing application for a biological product that can be demonstrated to be “highly similar” (biosimilar) to, or interchangeable with, a reference product licensed under section 351(a) of the PHS Act may submit a 351(k) application.
Response at 5. The authors of the FDA Law Blog have written an interesting post about this and two earlier Citizen Petition Responses concerning biosimilars: You Had Us At “Biosimilars,” FDA; Agency Ties Up Yet Another Biosimilars Loose End With Petition Response Concerning Certain “Biological Drugs.”
We’re still awaiting the first biosimilar litigation and/or approval under the BPCIA to see whether the biosimilar route is truly going to be an attractive opportunity in the U.S.
Mayo v. Prometheus Limits Diagnostic Test Patenting
Tuesday the Supreme Court unanimously decided Mayo Collaborative Services v. Prometheus Labs, a decision of considerable significance to the diagnostics industry.
The Court reversed the Federal Circuit Court of Appeals, which had held that patent claims to “a method of optimizing therapeutic efficacy” for treatment of a specific disorder with the steps of (a) administering a specific drug; (b) determining the level of a metabolite of the drug in the patient; wherein the dosage of the drug should be increased or decreased if the level of the drug is outside of a specified range, were patentable under the §101 utility requirement.
Genetic Engineering & Biotechnology News Poll Shows Dissatisfaction with U.S. Progress on Biosimilars
Genetic Engineering and Biotechnology News published the results of a survey today showing that among their readers, 62.7% said they were “not much" satisfied with progress toward bringing biosimilars to the U.S. market. We'll see whether the recent publication of the draft guidelines stokes enthusiasm for the biosimilar regulatory pathway.
New Chapter in Decade Long Patent Fight Among DNA Diagnostics Leaders
Enzo Life Science’s U.S. Patent No. 6,992,180 entitled “Oligo- or Polynucleotides Comprising Phosphate-Moiety Labeled Nucleotides” (“the ’180 patent”) issued in January of 2006. The patent traces back to an application filed in June 1982. After a series of continuation applications, a June 7, 1995 filing ultimately gave rise to the ’180 patent. Because it was filed just before the GATT treaty effective date, the ‘180 patent will expire in 2023 — 17 years from the day the patent issued and 41 years after the original patent filing.
FDA Releases Biosimilars Guidance
Yesterday the FDA released its long-awaited draft guidance on biosimilar development:
2012-02-09 FDA Press Release re Draft Guidance on BioSimilar Product Development.pdf
Scientific Considerations in Demonstrating Biosimilarity to a Reference Product.pdf
Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product.pdf
