By Kurt R. Karst –
For months we have been waiting with bated breath for the promised January 2015 release of a discussion draft of legislation to implement the 21st Century Cures Initiative, which was launched in April 2014 by now-Chairman of the House Energy and Commerce Committee Representative Fred Upton (R-MI) and Committee Member Representative Diana DeGette (D-CO). That wait came to an end on January 27, 2015 when an announcement was posted on the Committee website stating: “21st Century Cures Legislative Phase Now Underway.” The Committee released a nearly 400-page discussion draft of the 21st Century Cures Act, a 13-page section-by-section summary of the draft bill, a 7-page white paper, and a 1-page discussion document.
The release of the discussion draft was immediatly acknowledged by several organizations, including the Advanced Medical Technology Association, the National Health Council, United for Medical Research, Research!America, the Biotechnology Industry Organization, and the Pharmaceutical Research and Manufacturers of America, and by some Members of Congress (here and here). Most folks still need time to digest the discussion draft, but don’t seem to be dissatisfied with the first draft; however, there is a growing opposition to the draft bill. The Generic Pharmaceutical Association issued a press release stating that the organization “is deeply disappointed in [the] discussion draft” and that “in its current form, the bill would upset the important balance between creating competition and encouraging innovation in the pharmaceutical marketplace, putting savings at risk and limiting access to affordable medicines for millions of American patients.” In addition, Representative DeGette and Representative Frank Pallone (D-NJ), Ranking Member of the Energy and Commerce Committee, expressed their disappointment with the draft. In a press release, Representative DeGette said: “While I don’t endorse the draft document, I know that with continued engagement, we can reach a bipartisan consensus to help advance biomedical research and cures.” Meanwhile, Representative Pallone said in a press release that he is “disappointed that the discussion document released today by Chairman Upton does not reflect true bipartisan collaboration,” and that “[i]n its current form, I am concerned that the nearly 400 page draft could create more problems for our health care system than it solves.”
Like many others, we’re still poring over the draft bill, some sections of which include a placeholder for draft text that will be added in the coming weeks, but we found some time to put together a post on the draft legislation. We’re certain to have additional posts on the bill – or on specific sections of the bill – in the weeks and months ahead as we learn more and as the 21st Century Cures Act takes greater shape while it moves through the legislative process.
The 21st Century Cures Act is chock-full of proposals, some of which are new and some of which are old (i.e., based on or inspired by previously introduced legislation), from various stakeholders. As noted in the Energy and Commerce Committee’s discussion document:
Over the course of the last year, patients, providers, innovators, regulators, and researchers from around the country have provided a wide range of specific ideas on how Congress can help accelerate the discovery, development, and delivery of promising new treatments and cures for patients and maintain our nation’s standing as the biomedical innovation capital of the world. While it remains a work in progress, the legislative language included in the discussion document is based on such ideas, including proposals authored by both Republicans and Democrats.
The 21st Century Cures Act discussion draft has 5 titles. Each title includes a series of proposals covering a wide range of drug, biologic, and medical device topics – from various “push” and “pull” incentives (see here and here), to orphan drugs, to clincial trial requirements, to social media, to controlled substances, to reimbursement, to . . . well, you get the idea: there’s a lot in the draft bill! Here’s the title framework from the discussion draft:
TITLE I – PUTTING PATIENTS FIRST BY INCORPORATING THEIR PERSPECTIVES INTO THE REGULATORY PROCESS AND ADDRESSING UNMET MEDICAL NEEDS
TITLE II – BUILDING THE FOUNDATION FOR 21ST CENTURY MEDICINE, INCLUDING HELPING YOUNG SCIENTISTS
TITLE III – MODERNIZING CLINICAL TRIALS
TITLE IV – ACCELERATING THE DISCOVERY, DEVELOPMENT, AND DELIVERY CYCLE AND CONTINUING 21ST CENTURY INNOVATION AT NIH, FDA, CDC, AND CMS
TITLE V - MODERNIZING MEDICAL PRODUCT REGULATION
Some of the interesting items this blogger tagged while going through the draft legislation are identified below (with subtitle or section and page number references to the discussion draft); but note that because of this blogger’s penchant for all things related to drug regulation (and especially the Hatch-Waxman Amendments, the Orange Book, and the Biosimilars Act), the items tagged below reflect my interest in those topics over other topics (though that doesn’t mean other topics aren‘t interesting . . . just that they’re probably more interesting to others with different predilections and expertise in those matters).
Title I of the draft bill includes an array of proposals intended to incorporate patient perspectives into the regulatory process and to help address their unmet medical needs. This goal would be accomplished in part by requiring that a “structured risk-benefit assessment framework” be built into the new drug approval process that includes the development and use of patient experience data to facilitate a balanced risk-benefit consideration, and the development and implementation of “a consistent and systematic approach to the discussion of, regulatory decisionmaking with respect to, and the communication of, the benefits and risks of new drugs” (Section 1001; pages 8-15).
Other sections of Title I further provide for surrogate endpoint qualification and use, and the qualification of other biomarkers (Subtitle B 1021; pages 15-28); modify the breakthrough therapy evidentiary standard and other provisions in FDC Act § 506 (Subtitle C; pages 29-34); foster the development of new antibiotics along the lines of the Antibiotic Development to Advance Patient Treatment Act (“ADAPT Act”) (see our previous post here) and the Developing an Innovative Strategy for Antimicrobial Resistant Microorganisms Act (“DISARM Act”) (Sections 1061-1064; pages 34-72); require greater transparency for expanded access programs (Subtitle G; pages 82-91); and allow for streamlined data review so that the sponsor of an approved prescription drug can submit “qualified data summaries” in a supplemental application for approval of a “qualified indication” (i.e., “an indication for the detection, diagnosis, prevention, treatment, or cure of cancer,” or other types of indications identified by FDA) (Subtitle J; pages 94-98). The bill's provisions on antibiotic development may be considered in tandem with a proposal that will be included in the President’s 2016 Budget. The White House laid out that multi-pronged proposal to combat antibiotic resistance in a fact sheet released on January 27th.
As expected (see our previous post here), several provisions in the draft bill (Title I) would also create new patent and non-patent exclusivity opportunities. Continuing a trend of “exclusivity stacking” started in 1997 with the creation of 6-month pediatric exclusivity, the draft Cures Act would extend a period of 3-year new clinical investigation exclusivity by 2 years if the NDA sponsor provides documentation to FDA demonstrating that:
(I) the new clinical investigations essential to the approval of the application or supplement and conducted or sponsored by the person submitting the application or supplement support the approval of a new indication or use for the drug that is the subject of the application or supplement; or
(II) the drug that is the subject of the application or supplement has been reformulated or redesigned so that the drug can reasonably (as determined by the Secretary in consultation with the person submitting such application or supplement) be expected—
(aa) to promote greater patient adherence to an approved treatment regime relative to the previously approved formulation or design of the drug;
(bb) to reduce the public-health risks associated with the drug relative to the previously approved formulation or design of the drug;
(cc) to reduce the manner or extent of side effects or adverse events associated with the previously approved formulation or design of the drug;
(dd) to provide systemic benefits to the health care system relative to the previously approved formulation or design of the drug; or
(ee) to provide other patient benefits that are comparable to the benefits described in items (aa) through (dd).
We can envision several instances in which this provision (Subtitle M; pages 118-122), if enacted, might come into play, including with the development of abuse-deterrent formulations of opioids.
Another exclusivity stacking provision would provide a 6-month extension to the 5-year new chemical entity, 3-year new clinical investigation, and 7-year orphan drug exclusivity periods available to drug products approved under the FDC Act (and to patents listed in the Orange Book for a drug), and to the 4-year and 12-year reference product exclusivity and 7-year orphan drug exclusivity periods available to biological products licensed under the PHS Act if a sponsor obtains approval of a drug or biological product for a “new indication for use of the drug to prevent, diagnose, or treat [a designated] rare disease or condition.” This provision (Subtitle N; pages 123-131) appears to be intended to address the situation where a product shows potential to prevent or treat both a prevalent and an orphan disease, but it is developed first (and perhaps only) for the prevalent disease. As a result, many patients with orphan diseases don’t have viable access to potentially beneficial drugs because the drugs are approved only for the prevalent disease. Indeed, there are numerous examples of drugs approved for a prevalent indication that are also used as an effective off-label treatment for patients with orphan diseases. Clonidine is one such example. It is approved for the treatment of high blood pressure, a prevalent disease, but clonidine can also be used to treat Tourette’s Syndrome, an orphan disease. Clonidine, however, has never been developed for that orphan use. The 6-month incentive provided by this provision in the draft bill would target a situation like that.
The draft Cures Act also includes provisions (Subtitle L; pages 101-118) modeled after the Dormant Therapies Act of 2014 (S. 3004), which Senator Orrin Hatch (R-UT) introduced last December. The Dormant Therapies Act is a redo of the Modernizing Our Drug & Diagnostics Evaluation and Regulatory Network Cures Act (“MODDERN Cures Act”), which was introduced in 2013 (H.R. 3116) and 2011 (H.R. 3497). Among other things, the draft Cures Act would create a new guaranteed 15-year “protection period” for certain drug and biological products designated and approved as dormant therapies. As part of the deal, however, companies must agree to waive patent rights.
In what is a rather innovative way to approach the concept of “wildcard exclusivity” (see our previous post here) the draft Cures Act would amend the Generating Antibiotic Incentives Now Act (“GAIN Act”) (FDC Act § 505E), which amended the law to include a 5-year marketing exclusivity add-on for a drug product designated and approved by FDA as a Qualified Infectious Disease Product, to allow a sponsor to convey a portion of its exclusivity (currently pegged at 12 months) to apply with respect to one or more other drugs (Section 1063; pages 59-68). Such conveyance – which could include the sale of exclusivity from one company to another company – would also apply to Orange Book-listed patents. But there’s a catch! In addition to certain cutoff periods for conveyance, the sponsor of an application to which exclusivity has been conveyed must make donations to the National Institutes of Health and to a “bona fide, independent patient assistance program.” The amounts of the donations are still being ironed out, but donation amounts would not exceed 5% of sales of the recipient drug in the United States for a defined period and for a yet-to-be-determined total donation.
Other topics of interest in other titles of the discussion draft include:
- Provisions concerning genetically targeted platform technologies for rare diseases under which accelerated approval is available based on the extrapolation of evidence that is reasonably likely to predict clinical benefit of a product (Section 2051; pages 150-153);
- Revisions to human subject research regulations (Section 3001; pages 223-231);
- The requirement that FDA “establish and implement a framework through which sponsors of drugs, biological products, or devices may submit to the Secretary a proposal for the incorporation of adaptive trial designs, Bayesian methods, or other alternative statistical methods into proposed clinical protocols and marketing applications for drugs, biological products, or devices” (Section 3021; pages 232-235);
- Changes to the Tropical Disease Priority Review Voucher provisions of FDC Act § 524 that broaden the voucher program to infectious diseases (Section 4045; pages 267-271);
- In what seems likely be a nod to President Obama’s announcement at the 2015 State of the Union Address of the creation of a new precision medicine initiative, the Cures Act includes a placeholder for text on “Precision Medicine” (Section 2301; page 223);
- FDA succession planning (Section 4121-4122; pages 280-282); and
- A lot, lot more . . . .
We’ll end this post with one more exclusivity provision included in the draft Cures Act. Unlike all of the other exclusivity provisions in the draft bill, this last provision applies to generic drugs and biosimilars. Tucked away in Title V of the draft legislation (Section 5001; pages 347-349), it gives FDA the authority to designate a drug or biological product as an “American-manufactured drug.” Such a designation means, with certain limitations, that 180-day exclusivity applicable to generic drugs and the 1-year, 18-month, or 42-month period granted (as applicable) to an interchangeable biosimilar biological product will be extended. The amount of that extension is still being debated, however.
As Porky Pig would say at the conclusion of a Looney Tunes cartoon, “That’s All Folks!”