Breakthrough Therapy Pathway A Success for CDER in 2013

The FDA’s new breakthrough therapy designation has exploded in popularity, the agency says. As of Nov. 22, 108 requests for breakthrough designation have been submitted. The FDA has granted 34, denied 51 and approved three breakthrough products already. The remaining 20 breakthrough requests still await the agency’s decision on the designation.

Richard Moscicki, CDER deputy director for science, says the majority of drugs that have applied as breakthroughs are in the hematology/oncology and antiviral fields.

Speaking at the FDA/CMS Summit in Washington, D.C., Moscicki said CDER viewed the new expedited approval pathway that was created under the FDA Safety and Innovation Act (FDA-SIA) as one of CDER’s highlights of 2013.

Moscicki also touted the agency’s progress under the Generat-ing Antibiotics Now Act, which was also part of FDASIA. The FDA

Senate Vote on Budget Deal Offers Two-Year Protection for User Fees

The Senate last week voted 64-36 to approve a budget that will protect FDA user fees from sequestration cuts for the next two years.

The bill stops sequestration of all discretionary spending for 2014 and 2015, which includes the FDA’s user fees.

The House has already passed the budget act and it now moves on to President Barack Obama, who is expected to sign it. The act lays out broad limits for total government spending, but it’s unclear yet what the FDA’s final budget will be.

The House and Senate appropriators now have until Jan. 15, 2014 to work out a deal on how funding from the bill will be distributed. That’s when current federal funding runs out.

Vol. 45, No. 50Dec. 23, 2013

HHS rejects PhRMA plea to annul 340B orphan drug discount rule ............Page 2

FDA Calendar ..........Page 2

GSK reforms sales practices in wake of China scandal .....................Page 3

Comings & Goings ..Page 4

FDA FOIA Log ........Page 4

Lawmakers propose bill to ban pay-for-delay deals .........................Page 5

Four-in-five breakthrough requests denied by CBER .......................Page 6

FDA extends comment period for generic safety labeling rule .............Page 7

FDA, EMA extend joint inspections to generic applications ..............Page 9

PhRMA wary of FDA’s call for antibacterial superiority trials .......................Page 12

Editor’s Note: Due to the holidays, Washington Drug Letter will not be published on Dec. 30, 2013. The next issue will be published Jan. 6, 2014.

INsIde thIs Issue

(See Budget, Page 4)

(See Breakthrough, Page 6)

Washington Drug Letter Dec. 23, 2013Page 2

HHS Rejects PhRMA Plea to Annul 340B Orphan Drug Discount Rule

HHS stands by its final rule expanding 340B discounts to orphan drugs when certain hospitals and healthcare providers use them to treat non-rare diseases, the agency said in a court filing opposing PhRMA’s attempts to invalidate the rule.

HHS, in a brief filed Dec. 13, says that Con-gress specifically directs the agency to deter-mine which drugs will be eligible for discounts under the federal 340B program when they are purchased by hospitals and clinics that treat low-income and uninsured patients. While the agency says it intends to require entities covered under the discount program to pay full price for an orphan drug when it is used to treat a rare dis-ease, Congress has given it the discretion to dis-count those drugs in other cases.

Further, the agency says that the discounts are consistent with other regulations that address orphan drug incentives.

PhRMA is challenging HHS’ orphan drug rule that went into effect Oct. 1 (WDL, July 29). Orphan drugs had previously been exempt entirely from the 340B program, which requires drugmakers to provide certain outpatient drugs at a sizeable discount to certain covered entities.

PhRMA says Congress intended to exempt orphan drugs from the program for any use in an effort to preserve incentives for orphan drug development for rare diseases. Citing “irreparable harm” to its members’ bottom lines, the group’s lawsuit challenges HHS’ authority to issue the rule and asks the U.S. District Court for the Dis-trict of Columbia to invalidate it.

PhRMA says the new rule undermines incen-tives drugmakers receive for developing orphan drugs. PhRMA remains “confident in its case,” spokeswoman Liz Magsig told WDL Dec. 17.

The group has until Jan. 10 to respond to HHS’ court filing. The briefing period of the case, which is filed in the U.S. District Court for the District of Columbia, will end Jan. 17, Magsig said. — Melissa Winn

Upcoming meetings through Jan. 15:

● Jan. 6-7: The FDA will hold the public workshop Complex Issues in Developing Drug and Biological Products for Rare Diseases. Silver Spring, Md.

● Jan 14: The Cardiovascular and Renal Drugs Advisory Committee will meet to discuss Chelsea Therapeutics’ NDA for Northera (droxidopa capsules) as a treat-ment of symptomatic neurogenic ortho-static hypotension in certain patients. Silver Spring, Md.

● Jan 15: The Cardiovascular and Renal Drugs Advisory Committee will meet to discuss Merck’s NDA for Zontivity (vora-paxar sulfate) for use in patients with a history of myocardial infarction. Silver Spring, Md.

● Jan 15: The Cardiovascular and Renal Drugs Advisory Committee will meet to discuss Janssen’s sNDA for Xarelto as a treatment to reduce the risk of thrombotic cardiovascular events in patients in the first 90 days after suffering acute coro-nary syndrome. Silver Spring, Md.

Comment deadlines through Jan. 1:

● Dec. 23: Comments due on draft guid-ance for industry Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment, docket no. FDA-2013-D-1170-0001.

● Dec. 23: Comments due on the draft guid-ance Elemental Impurities, docket no. FDA-2013-D-1156-0001.

● Dec. 30: Comments due on the FDA’s pro-posed study of direct-to-consumer promo-tions directed at adolescents, docket no. FDA-2013-N-1151-0001.

● Jan. 1: Comments due on the FDA’s pro-posed pilot project to test an automated NDA/ANDA field alert report form, dock-et no. FDA-2013-N-0294-0001.

FDA CAlENDAR

Washington Drug LetterDec. 23, 2013 Page 3

GSK Reforms Sales Practices In Wake of China Scandal

GlaxoSmithKline unveiled a new compen-sation system for its global sales force this week in a move hailed as a revolutionary change to improve ethical practices for drug sales profes-sionals. But so far it’s a revolution of one.

The company announced it will stop compensat-ing sales personnel worldwide based on sales targets and cease paying physicians to speak about its prod-ucts; a drastic shift away from its industry peers.

The new sales and marketing practices come in the wake of an alleged bribery scheme in China where officials claim sales teams gave kickbacks to doctors, hospitals and associations to boost sales and prices of GSK drugs (WDL, Sept. 9).

The changes to be implemented globally over the next three years were piloted in the United States, Mary Anne Rhyne, a spokeswoman for the UK drugmaker, told WDL last week. Since 2011, GSK’s U.S. division has paid sales people a base salary and a bonus based on their scientific knowledge, business acumen and their value to physicians, Rhyne said.

GSK’s U.S. division also hasn’t paid physicians to attend medical conferences for the past couple of years, but has paid physicians to speak about its products. The company will instead fund physicians through independent, unsolicited educational grants.

The drugmaker says it aims to implement the compensation system in all countries by 2015 and the physician payment changes by 2016. So far, industry is not jumping to follow GSK’s lead.

PhRMA was ambivalent about GSK’s announcement, saying only that it is one path drugmakers can take to ensuring appropriate relationships with physicians.

The trade group has a code of conduct for medical conferences, which states that giving any subsidy to a physician “may be viewed as an inappropriate cash gift.” PhRMA recommends a drugmaker submit funding to the conference’s sponsor, which can use the money to reduce the

overall registration fee for all attendees. It is silent on the issue of compensation.

Amgen told WDL it follows PhRMA’s code of conduct. Eli Lilly also follows PhRMA’s code. Both offer pay-for-performance packages for employees.

Novartis also offers pay-for-performance. Its ethics policy says the company may pay a physi-cian’s travel, meals, accommodations and reg-istration fees for a conference, but not for time spent. — Robert King

New Compounding laws Don’t Change FDA Position on Makena

The FDA does not intend to prevent com-pounders from making preterm birth drug Makena (hydroxyprogesterone caproate), the agency stated in a legal filing earlier this month that outlines how it intends to approach one con-tentious issue involving compounders.

Drugmaker K-V Pharmaceuticals, which won approval for the drug in 2011 and put a $1,500 per dose price on it, has sued the agency to force it to prevent compounders from duplicating its drug unless they have received a prescription for it.

K-V recently filed a brief in K-V Pharmaceu-ticals v. FDA in the U.S. Court of Appeals for the District of Columbia, reviving its arguments against the agency’s decision. The new Drug Quality and Security Act prohibits the compounding of the drug because it is made in batches and “commonly before receipt of a prescription,” the drugmaker argued.

In a response letter filed in the case last week, the FDA said it expects to employ a risk-based enforcement approach to compounding — an approach unaltered by the recent law and agency guidance to pharmacy compounders — and it does not intend to change its approach to Makena.

The law provides for compounding in limited quantities before the receipt of a valid prescrip-tion order “if it is based on a history of the phar-macist receiving valid prescription orders for the drug,” the FDA says in its Dec. 12 letter to the court. — Melissa Winn

Washington Drug Letter Dec. 23, 2013Page 4

Comings & GoingsThe FDA has formally appointed Ellen Mor-

rison to serve as assistant commissioner for oper-ations, a position Morrison has held in an acting capacity since Oct. 1, 2012. When her appoint-ment becomes effective Dec. 29, she will leave her current position as the director of the agen-cy’s Office of Crisis Management in the Office of the Counselor to the Commissioner.

Amarin has appointed its president, John Thero, to serve as the drugmaker’s new presi-dent and chief executive officer. Lars Ekman, Amarin’s lead independent director, has also been appointed chairman of the board. Thero and Ekman will assume their new roles Jan. 1, when Joseph Zakrzewksi will retire from the positions. Zakrzewski will remain on Amarin’s board.

Pfizer’s Amy Schulman is leaving the com-pany. The drugmaker has named Albert Bourla to replace her as head of the vaccines, oncology and consumer healthcare business unit.

TherapeuticsMD has hired pharma veteran Joel Krasnow to be its chief scientific officer. Previously, Krasnow was chief safety officer at Intarcia Therapeutics. Before that, he held execu-tive positions at Eisai and Novartis. He has also worked at Pfizer and Organon.

House and Senate appropriators are expected to provide the FDA a modest fiscal 2014 fund-ing boost over its $4 billion fiscal 2013 operating level, in line with recent congressional proposals, Ellie Dehoney, vice president of policy and advo-cacy at Research!America says.

“The Senate’s decision to release user fees paid by our members to the FDA will help speed the delivery of breakthrough products and tech-nologies to the patients who need them most,” said Jim Greenwood, president of the Biotech-nology Industry Organization. “Allowing the FDA full access to these privately paid fees will provide the agency with the resources it needs to keep pace with scientific advances while also safeguarding patient safety.”

The industry group is also calling on Con-gress to pass Senate legislation (S.1413) spon-sored by Sens. Mark Pryor (D-Ark.) and Roy Blunt (R-Mo.), and a House bill (H. 2725) spon-sored by Reps. Leonard Lance (R-N.J.) and Anna Eshoo (D- Calif.), that would prevent all future user fees from being sequestered (WDL, July 22).

Some $85 million in sequestered fiscal 2013 user fees currently remain out of reach to the FDA and require targeted legislation for their recovery. — Ferdous Al-Faruque

Date Requester Requested Information11/12/2013 AccelaPHARM Adverse event reports for Ariad’s Iclusig (ponatinib)

11/13/2013 Marathon Pharmaceuticals Form 483s for Wockhardt from July 2013 to November 2013.

11/13/2013 Shire Human Genetic Therapies Establishment inspection report from 6/2/2011 for Shire’s Belmont, Mass. facility.

11/14/2013 Reckitt Benckiser Adverse event reporting system summary for Eli Lilly’s Cialis (tafadil).

11/14/2013 Dava PharmaceuticalsQuality assurance profile and establishment inspection report from 2012 for Chartwell Pharmaceuticals’ Congers, N.Y., facility.

Budget, from Page 1

FDA FOIA lOG

The FDA received 198 FOIA requests the week of Nov. 11 including the following.

View the complete FOIA log for the week of Nov. 11 at www.fdanews.com/ext/resources/files/12/12-19-13-FOIALog.pdf.

Washington Drug LetterDec. 23, 2013 Page 5

lawmakers Propose Bill To Ban Pay-for-Delay Deals

U.S. lawmakers Dec. 11 introduced legisla-tion that would prohibit patent litigation settle-ments in which a brand drugmaker compensates a generic drugmaker to delay sales of a compet-ing generic drug, commonly referred to as “pay-for-delay” deals.

The Protecting Consumer Access to Generic Drugs Act of 2013, introduced by Rep. Bobby Rush (D-Ill.), would deem the deals an “unfair and deceptive act or practice” that creates an unfair method of competition, an offense prose-cutable under the Federal Trade Commission Act.

The bill would be a boon to the FTC after a Supreme Court decision this summer made pros-ecuting pay-for-delay agreements an uphill battle.

As part of a heavily anticipated ruling in the case FTC v. Actavis, the high court ruled 5-3 that pay-for-delay agreements are not presumptively illegal, but instead should be evaluated on a case-by-case basis under a long-standing antitrust test called the “rule of reason” (WDL, June 24).

The FTC said at the time the ruling would not dampen its efforts to pursue antitrust charges against drugmakers, but instead would prompt the agency to heighten its scrutiny of patent liti-gation settlements between brand and generics manufacturers (WDL, July 29).

The Rush bill has been referred to the House Energy & Commerce Committee and the House Committee on the Judiciary.

While the U.S. debates changes to law, the EU continues moving ahead with enforcement against pay-for-delay deals. The European Com-mission last week announced its latest pay-for-delay enforcement case. It has fined Novartis and Johnson & Johnson $22 million for delaying mar-ket entry in the Netherlands of a generic fentanyl patch, a painkiller used by cancer patients.

The Commission also announced on Dec. 10 it is investigating Servier and other pharma

companies for potentially delaying the market entry of generic perindopril, a cardiovascular drug, and an agreement between Cephalon and Teva that possibly delayed the entry of generic modafinil, a medicine for sleeping disorders.

The Protecting Consumer Access to Generic Drugs Act of 2013 can be viewed at www.fdanews.com/ext/resources/files/12/12-13-13- Generics-Act.pdf. — Melissa Winn

Public Citizen Raises Conflict of Interest Concerns for Advisors

A citizen watchdog group is again raising concerns about conflicts of interest on FDA advi-sory committees, charging that the agency should not have allowed a panel member to vote on a drug that a family member was taking.

Deanna Cisneros served as the patient represen-tative for the Endocrinologic and Metabolic Drugs Advisory Committee’s Nov. 19 meeting on Bioma-rin’s Vimizim (elosulfase alfa), an orphan drug for the treatment of Mucopolysaccharidosis Type IVA.

Cisneros told the FDA beforehand that her daughter was taking the drug as part of a clini-cal trial, and the agency allowed her to remain on the committee, Sidney Wolfe, founder and senior advisor for Public Citizen’s Health Research Group, told WDL Dec. 16.

Cisneros, a registered nurse with Hous-ton Physicians Hospital, was one of 18 out of 21 panel members who voted to recommend approval of Vimizim (WDL, Nov. 25).

Wolfe, who served for four years on an agency advisory committee, said that Cisne-ros should not have participated because of the apparent conflict of interest. “There is no possi-bility that a person will say my daughter is taking this, but it shouldn’t be approved,” he said.

He added that it isn’t unusual for a patient or parent to speak during the public session, but “to go beyond that and have this person participating

(See Watchdog, Page 10)

Washington Drug Letter Dec. 23, 2013Page 6

granted 30 qualifying infectious disease product (QIDP) designations for 19 unique chemical enti-ties in 2013. QIDP provides priority review status and an extra five years of exclusivity for innova-tive antibiotics.

Looking ahead to 2014, Moscicki says he expects compounding will be a major focus for CDER as it works to begin overseeing more compounders.

The FDA started fast out of the gate when the Drug Quality and Security Act was signed into law last month. The agency already issued draft guidance on how “outsourcing facilities” can vol-untarily register with the FDA and report product information (WDL, Dec. 6).

In 2014, Moscicki said the FDA will work on establishing current good manufacturing prac-tices for outsourcing facilities and work with states to enhance joint cooperation in oversight of compounding. — Robert King

Breakthrough, from Page 1Four-in-Five Breakthrough Requests Denied By CBER

While FDA’s CDER breakthrough therapy desig-nations for new drug products have taken off dra-matically, CBER has been a lot more conservative in approving applications for the new designation.

Since the FDA rolled out the new expedited review category last year, CBER has received 15 requests for breakthrough designation. It has denied 12, ap-proved one and has yet to give a decision on two.

The news comes on the heels of CDER touting that, as of Nov. 22, it had received 108 break-through designation requests, granted 34, denied 51 and had already approved three products based on the designation.

Breakthrough Therapy Designation was writ-ten into law as part of the 2012 Food and Drug Administration Safety and Innovation Act and is intended for serious and life-threatening dis-eases. Under the law, the agency is required to give sponsors a ruling on whether or not to grant breakthrough designation within 60 days, and if approved, sponsors receive the benefits of fast-track designation, including expedited review.

To qualify for breakthrough designation, the drug or biologic has to treat a serious or life-threat-ening disease where existing therapies are not sufficiently effective.

CBER spokesperson Paul Richards told WDL the agency had not identified any single deficiency that was leading to rejections. However, he did reiterate that the FDA strongly recommends companies speak with the agency in advance of making submissions to avoid confusion in the ap-plication process.

Earlier this summer, the FDA released a much-anticipated guidance outlining what the designation entails (WDL, July 1). While Pharma has asked the agency to broaden its criteria for breakthrough des-ignation (WDL, Sept. 2), researchers have warned the FDA’s push for more expedited reviews could be putting patients in danger (WDL, Nov. 4).

Drugs approved in 2008 under the FDA’s expe-dited drug approval program took on average five years of clinical development time to gain ap-proval, compared with seven and a half years for drugs under standard review, according to a study published in JAMA Internal Medicine. And expe-dited drugs were tested for efficacy in an average of 104 patients compared to 580 patients for stan-dard review, it adds. — Ferdous Al-Faruque

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Washington Drug LetterDec. 23, 2013 Page 7

EU lawmakers Advance Revised Trial Rules; Adoption Expected in Early 2014

An overhaul of clinical trial regulations in the EU took a big step forward Dec. 20 as officials paved the way for revised rules to replace the current clinical trial directive in early 2014.

The EU Parliament and Council of Ministers agreed on a draft of the EU’s revised clinical trial regulations, which would standardize rules across member states and increase trial transparency in sync with the European Medicines Agency’s (EMA) parallel push to boost access to trial data.

Key changes included in the draft revision include:

● An allowance for sponsors seeking mar-keting authorization to register trials through a single, publicly accessible EU database managed by the EMA;

● The establishment of a single authoriza-tion procedure for all clinical trials to speed the application assessment by all member states; and

● Increased uniformity on review times for product applications across member states.

The proposed draft also would expand informed consent procedures and establish mechanisms allowing the European Commission to intervene in member states or third countries to ensure the clini-cal trial rules are properly supervised and enforced.

The European Federation of Pharmaceutical Industries and Associations (EFPIA) welcomed the draft regulation, in particular its new pro-posed trial authorization timelines. If approved, the draft would require national authorities to make a decision on whether to approve a trial within 60 days, which can be extended another 50 days for certain complex drug products.

However, the European Association for Bioin-dustries or EuropaBio said it didn’t think the pro-posed timelines are aggressive enough to boost medical research in Europe.

“These extended timelines lack ambition and signal that there is little commitment to restoring

a competitive environment for conducting clini-cal research in Europe,” said the organization. “Including the timelines for questions and assess-ment of responses, the total assessment time-lines would actually be nearer to or in many cases exceeding 100 days.”

Transparency Provisions

The increased transparency rules in the draft law track closely with a plan proposed by the EMA, which has been delayed from implementa-tion until after a March 2014 meeting.

As proposed, the draft regulations would require sponsors to publish summary results of clinical trials to the EU database in layperson terms within a year of completing a trial. Sponsors would also have to submit clinical study reports within 30 days of receiving marketing authorization. Sponsors

FDA Extends Comment Period For Generic Safety labeling Rule

The FDA has extended by 60 days the com-ment period for its proposed safety labeling rule for generic drugs. Stakeholders now have until March 13 to comment on the proposal, which would allow generic drugmakers to update labels in response to safety issues without agency approval.

GPhA earlier this month asked the FDA for more time to analyze the proposal, noting the sig-nificant legal and commercial challenges it would present for its members (WDL, Dec. 6).

Current rules allow generic drugmakers to update labeling only to conform with any changes that are made to the brand-referenced drug’s label. GPhA has voiced concern the proposed rule would lead to multiple generic drugmakers filing con-flicting safety information for the same generic product, leading to “unnecessary confusion and uncertainty for prescribers and patients.”

The group has also questioned whether the FDA has the authority to issue the proposed rule. — Melissa Winn

(See Transparency, Page 10)

Washington Drug Letter Dec. 23, 2013Page 8

Gilead Moves Closer To Dominating Hep C Market

Gilead Sciences’ drug Sovaldi appears primed to dominate the hepatitis C market with the release of new Phase III trial data showing subjects with genotype 1 of the virus benefit from the drug, without coupling it with interferon.

Genotype 1 is the most prevalent form of hepatitis C in the U.S., affecting about three-fourths of all patients. The FDA earlier this month approved Sovaldi (sofosbuvir) for the treatment of several hepatitis C genotypes with-out interferon — except for genotype 1.

The new Phase III trial data released Dec. 19 may change that as subjects in the trials suffering from hepatitis C genotype 1, many of whom were cirrhotic, showed overwhelmingly high response rates at weeks 8, 12 and 24 of the treatment regi-men with very few side effects.

The treatment involved a combination of Sovaldi and Gilead’s NS5A inhibitor ledipasvir with

and without ribavirin. Patients treated without riba-virin had even fewer side effects than those treated with the drug while maintaining a similarly high response rate over 90 percent, according to Gilead.

Gilead is finalizing regulatory filings to get Sovaldi and ledipasvir approved for hepatitis C genotype 1, and hopes to submit a new drug appli-cation to the FDA in the first quarter of 2014.

An approval would leapfrog the company past Janssen and Medivir, whose next-generation treatment Olysio (simeprevir), in combination with interferon and ribavirin, was approved by the FDA on Nov. 22 for Genotype 1 patients.

ISI Group analyst Mark Schoenebaum says the study results position Gilead to dominate the hepatitis C market, which the consultancy Deci-sion Resources predicts will grow from almost $3 billion in 2011 to more than $23 billion in 2018.

Besides the U.S., Sovaldi is approved in Can-ada and is pending approval in the EU, Switzer-land, Turkey, Australia and New Zealand. — Ferdous Al-Faruque

FDA To Require Clinical Studies for OTC Antibacterial Soaps, Washes

The FDA plans to mandate that manufac-turers of antibacterial soaps and body washes submit clinical outcome study data that address safety and efficacy of their products, regulating them as they would other OTC medications.

The agency Dec. 16 proposed a rule that would amend the 1994 tentative final monograph for over-the-counter (OTC) antiseptic drug products, but does not affect hand sanitizers, wipes or antibiotic prod-ucts used in hospitals or other healthcare settings.

Manufacturers of antibacterial soaps and body washes, however, will need to submit clini-cal outcome study data that address the agency’s concerns about:

● Long-term use of these products and anti-biotic resistance

● Hormonal effects; and ● Whether the product shows any greater

ability to reduce the spread of illness and

certain infections than simply washing with soap and water.

The FDA hopes to finalize the rule by Sep-tember 2016, Sandra Kweder, deputy director of CDER’s Office of New Drugs, said during a con-ference call. The rule would be effective one year after final publication.

Products that lack efficacy and safety data at that point will be deemed misbranded.

The proposed changes are part of the agen-cy’s larger efforts to review the widespread use of antibiotics in consumer products.

Comments on the proposed rule, docket no. FDA-1975-N-0012, are due June 16, 2014. The agency will allow companies and other inter-ested stakeholders to submit data and studies to be considered in the finalizing of the rule until Dec. 2014.

Read the text of the proposed rule at www.fdanews.com/ext/resources/files/12/12-16-13-OTC-Antiseptics.pdf. — Melissa Winn

Washington Drug LetterDec. 23, 2013 Page 9

FDA Continues to Defend Zohydro Approval, State Prosecutors Criticize

As more critics of the FDA’s approval of the painkiller Zohydro ER come forward, the agency says it will not limit approval of new opioid pain-killers to those with abuse-deterrent properties.

Attorneys general from 28 states this week sent FDA Commissioner Margaret Hamburg a letter blasting the agency’s October approval of Zogenix’s high-dose narcotic painkiller Zohydro ER (hydrocodone bitartrate extended-release cap-sules), saying it threatens to reinvigorate a tide of prescription drug abuse that law enforcement offi-cers and others are just now beginning to tame.

“We hope that the FDA either reconsiders its approval of Zohydro ER, or sets a rigorous time-line for Zohydro ER to be reformulated to be abuse-deterrent while working with other federal agencies to impose restrictions on how Zohydro ER can be marketed and prescribed,” they say.

The letter follows similar complaints voiced by a group of lawmakers two weeks ago. Reps. Ste-phen Lynch (D-Mass.), Hal Rogers (R-Ken.) and six of their colleagues urged the Zogenix drug be stripped of its approval until the company creates an abuse-deterrent formulation (WDL, Dec. 9).

Zogenix spokeswoman Julie Normart said the company is working on an abuse-deterrent for-mulation for Zohydro ER, and hopes to have it on the market within three years.

The drug was approved over the objection of FDA advisors who cited its “high potential for abuse” (WDL, Oct. 28).

While acknowledging the nation’s struggles with prescription drug abuse, the FDA says it doesn’t believe it “feasible or in the best inter-est of public health” to require all prescription opioids to be abuse-deterrent. In a response to a citizen petition filed by several anti-drug abuse advocacy groups published Dec. 12, CDER Director Janet Woodcock says abuse-deterrent technologies are fairly new and have limitations that shouldn’t stand in the way of approvals.

The FDA will continue to take a “product-by-product approach to regulatory decisions con-cerning the safety and effectiveness of opioid products,” Woodcock says in the letter.

Zohydro ER is the first approved sin-gle-entity hydrocodone product and the first extended-release/long-acting (ER/LA) product containing hydrocodone.

The attorneys’ letter to Commissioner Ham-burg can be read at www.fdanews.com/ext/resources/files/12/12-12-13-AG-Letter.pdf. Read the FDA’s citizen response letter at www.fdanews.com/ext/resources/files/12/12-12-13-CDER-Response.pdf. — Melissa Winn

FDA, EMA Extend Joint Inspection Initiative to Generic Applications

The FDA and EMA will expand their joint inspection activities to include facilities involved with bioequivalence studies for generic drug applications.

Regulators from the FDA, EMA and several EU member states will share information on inspec-tions of these facilities, conduct joint inspections of the sites and work together to train inspectors.

As part of the initiative, the regulators hope to speed up the identification of manufacturing problems that raise questions about the reliability of data submitted in bioequivalence studies used to verify that generic drugs are substitutable for their brand counterparts.

The program builds upon the successful FDA/EMA joint good clinical practices inspec-tion initiative launched in 2009.

Both programs were designed to help the regulators better “leverage inspection resources” to address the challenges of increased globaliza-tion in the pharmaceutical industry, according to CDER director Janet Woodcock.

An 18-month pilot phase of the generic drug application inspection initiative will launch Jan. 2.

The EU Member states participating in the program are France, Germany, Italy, the Nether-lands and the United Kingdom. — Melissa Winn

Washington Drug Letter Dec. 23, 2013Page 10

as a voting member and influencing discussion seems inappropriate.”

FDA spokesman Eric Pahon responded, however, that personal experience with a product either as a patient or caregiver doesn’t necessarily disqualify that person from advisory committee participation.

“Part of the patient representative experience is their unique perspective of patients and family members affected by a serious or life-threatening disease,” he said.

This is the second time in recent months that Public Citizen has raised conflict-of-interest con-cerns with the agency.

In October, Wolfe sent FDA Commissioner Mar-garet Hamburg a letter that included promotions for an industry conference featuring Lynne Drake, chair of the Dermatologic and Ophthalmic Drugs Advi-sory Committee. The promotional brochure said Drake will speak about what mistakes she has seen companies make when presenting to the committee.

Drake later withdrew from the conference and said she had neither seen the brochure nor would have approved it for distribution, Wolfe said.

According to Pahon, Drake told the agency about the conference prior to accepting that invi-tation. “FDA did not signal a concern, but our response was based on limited information,” he said. “It appears that Dr. Drake was not given a full understanding by the conference organizers of how she and her role at this conference would be characterized, and such a portrayal was incon-sistent with what she had agreed to.”

In his letter, Public Citizen’s Wolfe asked the FDA whether it has a policy surrounding committee members participating in such con-ferences. Pahon said the agency is crafting a response, but couldn’t say when it will be ready.

But Pahon stressed that the FDA does have guidance on determining conflicts of interest that would preclude someone from participating on an advisory panel. In addition, all advisory com-mittee members receive annual ethics training, which includes not using their public position for private gain, he said. — Robert King

that withdraw applications would still have to sub-mit those reports to the EU database.

While a key point of contention with industry has been the potential release of private patient data and commercially confidential information (CCI), the draft regulation reiterates the EMA’s position that CCIs cannot be considered confi-dential in light of public interest.

However, the draft does make certain excep-tions such as when it is necessary to protect patient privacy or protect communication between mem-ber states in relation to the preparation of assess-ment reports. It is unclear how the EMA plan would address the assessment reports issue.

EFPIA said it welcomed the legislators’ approach on the issue and added it reflects the EFPIA-PhRMA principles regarding “responsible” data sharing with researchers, patients and the public.

Read the EU draft regulation at www.fdanews.com/ext/resources/files/12/12-20-13-EU.pdf. — Ferdous Al-Faruque

Party Name Court Case Number Date Filed Most Recent

Action DateMost Recent

ActionCase Topic

PhRMA v. HHS

U.S. District Court for the District of Columbia

13-01501 9/27/13 12/13/13HHS filed re-sponse to PhRMA complaint

340B or-phan drug pricing

Watchdog, from Page 5

Transparency, from Page 7

tCOURT ACTIONS

Recent federal court actions involving the FDA and drug industry:

Washington Drug LetterDec. 23, 2013 Page 11

FDA’s OMP Shifts Staff RolesRachel Sherman, director of the FDA’s Office

of Medical Policy, is retiring. Denise Hinton will assume the role of acting OMP director and Leonard Sacks will serve as the acting OMP dep-uty director. Richardae Araojo will assume Hin-ton’s role as director of the Office of Medical Pol-icy Initiatives.

Janet Norden will also be leaving OMP to join the Office of the Commissioner’s Office of Planning and Policy. Melissa Robb will take Nor-den’s place as OMP’s associate director for regu-latory affairs.

FDA Allows Electronic PetitionsThe FDA is bringing the citizen petition pro-

cess into the 21st century by allowing for elec-tronic submissions, the agency says in a recent Federal Register notice.

Under the previous process, companies, law firms, advocacy groups and other interested par-ties submitted citizen petitions by way of writ-ten documents.

Petitioners may now submit documents elec-tronically, and only one copy of the submission is needed. The Division of Dockets Management will then assign it a unique docket number, mak-ing it easier to track the progress of a submission, the agency says.

The agency will still accept two copies of petitions on paper. Read the Federal Regis-ter notice at www.fdanews.com/ext/resources/files/12/12-19-13-CP.pdf.

FDA Approves GSK’s COPD DrugThe FDA on Dec. 18 approved GlaxoSmith-

Kline’s Anoro Ellipta, an inhaler-based treatment for chronic obstructive pulmonary disease (COPD).

The approval advances the first-ever once-daily dual bronchodilator to be approved for COPD in in the U.S., according to GSK. The approval follows a positive Sept. 10 advisory committee

recommendation and is based on seven Phase III clinical trials involving 6,000 COPD patients.

In announcing the approval, FDA officials lauded the drug as an alternative treatment for a disease that is the third leading cause of death in the U.S.

The drug carries a boxed warning of increased asthma-related death. GSK has submit-ted Anoro Ellipta for approval in the EU, Japan, Brazil and elsewhere.

Teva to launch Generic Viagra Pfizer will allow Teva to launch a generic

version of Viagra in the U.S. in 2017 — more than two years before the final patent on the drug expires — under a deal that settles a long-run-ning patent flap.

In return, Teva will pay Pfizer a royalty for a license to produce its generic version of the blockbuster erectile dysfunction drug.

A federal judge in 2011 ruled a method-of-use patent covering Viagra (sildenafil citrate) pro-tects the drug from generic competition well into 2019. A six-month extension for testing the drug in pediatric patients protects the drug until April 2020, Pfizer claims.

Viagra was approved by the FDA in 1998. The drug has annual sales of about $1.8 billion with nearly $1.2 billion from the U.S. alone.

Omeros Wins Orphan Drug DesignationThe FDA has granted Omeros orphan drug des-

ignation for its OMS721 human monoclonal antibody that targets the primary regulator of the immune lec-tin pathway, called MASP-2, and prevents comple-ment-mediated thrombotic microangiopathies.

The company is in the process of carrying out a Phase I trial of the drug. The highest dose of OMS721 delivered to date in that trial caused a high degree of inhibition of the lectin pathway. Further Phase I data is coming early next year, with Phase II studies beginning around the same time.

BRIEFS

Washington Drug Letter Dec. 23, 2013Page 12

PhRMA Wary of FDA’s Call for Antibacterial Superiority Trials

PhRMA is pushing back against the centerpiece of the FDA’s draft guidance on antibacterial drug development, saying superiority trials for antibacte-rials that treat drug-resistant infections are “neither routinely possible nor consistently ethical.”

It can be difficult to find a comparative treat-ment that is effective, a key part of a superiority trial, and unethical to use an ineffective or inad-equate comparative drug, the group said in com-ments on the guidance.

The trade group believes superiority trials should only be used when:

● There are high levels of resistance to all existing therapies;

● The only active therapy has significant toxicity issues; and

● An add-on to standard therapy is being developed.

PhRMA said that noninferiority trials, and trials that use alternative approaches to statistical inference testing, help to develop multiple drugs that treat the same indication.

This can help with patients who might have an allergy to one treatment or have an infection that is resistant to another treatment, the group said.

For example, Bayer commented that noninferior-ity trials can create misleading results, while superi-ority trials “by design show a meaningful difference which is unlikely to occur due to trial design issues.”

Another development approach in the guid-ance focuses on accelerated approval based on a surrogate endpoint that predicts a clinical bene-fit of the drug. PhRMA wants the FDA to define how exactly surrogate endpoints can be used alongside the types of endpoints typically used in antibacterial development.

“When considering the strength of evidence required for use of a surrogate endpoint, PhRMA encourages the FDA to account for the serious-ness of the condition and unmet medical need,” the group said.

FDA draft guidance proposes four drug development approaches to incentivize the devel-opment of antibacterials that treat drug-resistant infections (WDL, July 19). In addition to supe-riority, one of the development approaches calls for noninferiority trials intended to show that the drug is not worse than another treatment by a specific margin.

The guidance is part of the FDA and Congress’ efforts to address the dwindling pipeline of antibac-terials that treat serious and resistant infections.

A bipartisan bill was just introduced in the House that would allow drugmakers to sub-mit less data for antibiotics and antifungals that affect limited patient populations.

The comment period for the guidance, docket no. FDA-2013-D-0744, is closed. To read Anti-bacterial Therapies for Patients with Unmet Medical Need for the Treatment of Serious Bac-terial Diseases, visit www.fdanews.com/ext/files/07-02-13-Antibacterial.pdf. — Robert King

Reporters: Nick Otto, Elizabeth Orr, Ferdous Al-Faruque, Lena Freund, Robert King

President: Cynthia Carter; Content Director: Dan Landrigan; Executive Editor: Johnathan Rickman

Copyright © 2013 by Washington Business Information Inc. All rights reserved. Washington Drug Letter (ISSN 0194-1291), an executive briefing on the regulation of pharmaceuticals, is published weekly, 50 issues, for $1,347. Photocopying or reproducing in any form, includ-ing electronic or facsimile transmission, scanning or electronic storage is a violation of federal copyright law and is strictly prohibited with-out the publisher’s express written permission. Subscribers registered with the Copyright Clearance Center (CCC) may reproduce articles for internal use only. For more information, contact CCC at www.copyright.com or call (978) 750-8400.

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FDA Complete Response Letter Analysis:How 51 Companies Turned Failure to Success

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