WASHINGTON – Regeneron Pharmaceuticals Inc. is hoping Arcalyst can do what another IL-1 blocker couldn't do last year – wow the Arthritis Advisory Committee (AAC).

But, as it did with Novartis AG's Ilaris, the FDA is waving the safety flag ahead of Tuesday's AAC meeting on Arcalyst's (rilonacept) risk-benefit profile in preventing gout flares. This time, the agency is citing what may be a small increased risk of malignancies.

In briefing documents for the meeting, the FDA noted that six malignancies occurred in the Arcalyst arms of clinical trials, but none was seen with placebo. While such malignancies are typical in gout patients and the duration of Arcalyst treatment was relatively short, the agency said the imbalance suggests "the risk is small, but may be real."

Even though Regeneron is seeking a limited treatment duration for Arcalyst, the FDA expressed ongoing concerns about the use of chronic immunosuppressive therapy in gout. It's a concern that was raised last year when Ilaris (canakinumab), which stems from an old Regeneron-Novartis collaboration, took its run at the AAC. (See BioWorld Today, June 22, 2011.)

Novartis convinced the committee of Ilaris' efficacy as a gouty arthritis prophylactic, but it couldn't get past the safety issues, which included an increased risk of infections, and concerns over its protracted use as a gout prophylactic, given its long half life and extended pharmacodynamic effects. The committee voted 11-1 against approving the Swiss company's supplemental biologic license application (sBLA). The FDA followed AAC's advice and requested more data.

Now it's Arcalyst's turn. Like Ilaris, Arcalyst is an immunosuppressant first approved for cryopyrin-associated periodic syndrome, an orphan indication. While Arcalyst, a dimeric fusion protein, doesn't have the long half-life of Ilaris, a monoclonal antibody, Regeneron is seeking a narrower gout indication – prevention of gout flares in patients starting uric acid-lowering treatment. The proposed duration of treatment would be limited to 16 weeks.

The FDA's safety concerns did little to hurt Regeneron (NASDAQ:REGN), which recently posted its first profits in nearly a quarter of a century based on higher-than-expected first-quarter sales of age-related macular degeneration drug Eylea (aflibercept ophthalmic solution). Shares were down $2.27, less than 2 percent, closing at $131.67 Friday. (See BioWorld Today, April 27, 2012.)

Regardless of how the AAC handles the sBLA for Arcalyst, PiperJaffray analyst Edward Tenthoff said it won't have much of an impact on the Tarrytown, N.Y., company, since Eylea is its primary revenue driver.

Abbott Seeks Delay of Biosimilars

The first wave of biosimilars that's expected to hit the U.S. within the next few years would be pushed back out to sea if Abbott Laboratories Inc. is successful in erecting a seawall around biologic license applications (BLAs) submitted before Congress authorized the biosimilar channel.

In a citizen petition filed with the FDA last month, the Abbott Park, Ill., company asked the agency to refrain from activities involving biosimilars based on BLAs submitted before March 23, 2010, when the Biologics Price Competition and Innovation Act (BPCIA) was signed into law as part of the Affordable Care Act (ACA).

Since the development and approval of biosimilars would be based on trade secrets the innovator company shared with the FDA with the expectation that they would remain secret, Abbott said approving a biosimilar referencing pre-enactment BLAs is tantamount to an unconstitutional taking of private property.

If Abbott were to succeed with its seawall, the first wave of biosimilars could be pushed out beyond 2022, given the 12-year data exclusivity granted by the BPCIA.

While no biosimilar applications have been submitted yet, the FDA has said it expects the first one by the end of the year. As of Feb. 3, the agency had received nine investigational new drug (IND) applications for biosimilars. It also had received 35 requests for pre-IND meetings on 11 referenced biologics and had held 21 of those meetings. All of that activity is based on BLAs approved before BPCIA was passed. (See BioWorld Today, Feb. 6, 2012.)

Abbott said it didn't know whether any of those meetings involved its Humira (adalimumab), but it said at least three companies have started preclinical or clinical development of biosimilar versions of the blockbuster arthritis drug.

Of course, Abbott's petition could be moot if the Supreme Court rules the ACA's insurance mandate is unconstitutional and tosses the entire act because it lacks a severability clause. Such a clause, common to most legislation, allows one provision to be struck without damaging the rest of the act.

Federal Agencies to Think Globally

Once again emphasizing the dual mission of federal agencies such as the FDA in protecting public health and promoting economic growth and job creation, President Barack Obama issued an executive order last week calling on those agencies to clean house of regulatory approaches that get in the way of international harmonization.

The regulatory system must protect public health as well as promote economic growth, innovation, competitiveness and job creation, Obama said in the order, Promoting International Regulatory Cooperation. The administration also emphasized that dual role in its recent National Bioeconomy Blueprint. (See BioWorld Today, April 27, 2012.)

To help achieve those goals, the new executive order instructs federal agencies to eliminate unnecessary regulatory differences between the U.S. and other countries and to ensure they don't create more differences.

The order is intended to streamline regulatory requirements, eliminate pointless red tape and promote greater certainty in the regulation of drugs, nanotechnology and other regulated products, said Case Sunstein, administrator of the Office of Information and Regulatory Affairs.

In recent months, the U.S. has developed work plans with Canada and Mexico to reduce the regulatory barriers between the countries. The executive order will broaden those efforts globally.

While the Mexican plan deals primarily with food and other agricultural products, the Canadian work plan includes provisions to reduce duplicative costs for biopharma, minimize delays in drug approvals and streamline regulatory decisionmaking.

It specifically calls for a common electronic submission gateway for drug applications to both the FDA and Health Canada, increased collaboration in reviewing drugs, and enhanced collaboration in enforcement and compliance activities based on reliance on each other's inspection reports.

CMS Postpones the Sunshine

Citing the volume of comments, more than 300, that it received on a proposed rule implementing the Physician Payments Sunshine Act, the Centers for Medicare & Medicaid Services (CMS) is once again postponing when drugmakers must begin collecting information about their payments and gifts to doctors.

CMS said last week that it wouldn't require data collection before Jan. 1, 2013. That's a full year after the deadline set in the Affordable Care Act, which includes the sunshine provision. Meanwhile, CMS is working on the final rule, which it hopes to release later this year. (See BioWorld Today, Oct. 5, 2011, Oct. 27, 2011, and Nov. 3, 2011.)