Pharma news highlights: Novartis, J&J, Merck and more

Ed Silverman

Pharmalot

Ed Silverman provides us with his top news highlights from the pharma industry, including J&amp,J’s litigation settlement and Novartis’ manufacturing issues, over the past four weeks.

(Continued from “Pharma news highlights: July”)

In its quest to speed approvals and reward innovation, is the FDA green-lighting medicines with too many risks? An essay in the Journal of the American Medical Association argues that the agency may, in fact, be jeopardizing public health by relying too often on limited clinical trial data that, in some instances, has raised serious questions about safety. In doing so, the JAMA authors prompted a furious new installment in an ongoing debate.

“Although enabling new drugs with a favorable benefit-to-harm balance to become available to patients more rapidly is a laudable goal, the underlying question is what public health risks are taken when drugs are approved for widespread use while important safety questions remain unanswered.”

Thomas Moore, a senior scientist at the Institute for Safe Medicine Practice, and Curt Furburg, a health sciences professor at the Wake Forest School of Medicine.

They noted the FDA used various expedited approval programs for 16 of 35 new drugs, or 46 percent, endorsed in fiscal year 2011.

“All of the drugs received Priority Reviews, which provide shortened review times for drugs that may offer a therapeutic advance, 13 drugs were also designated for the Fast Track program that allows reviews to begin before clinical studies are complete for drugs that may fill serious unmet medical needs, and three drugs received Accelerated Approval, a program that relies on preliminary but not definitive evidence of benefit,” they wrote.

They offered three examples in which approvals were made – the Gilenya MS pill, the Pradaxa bloodthinner and the Caprelsa thyroid cancer treatment – but procedures and decisions appeared to place more emphasis on fast approvals than ensuring patient safety. The FDA, however, did not remain silent. The agency quickly issued a statement that said:

“Making regulatory decisions about drugs always involves uncertainty and risk. FDA works directly with the affected patient populations and treating physicians when considering just how much uncertainty and risk are reasonable to accept. We know, for example, that patients and physicians are willing to accept more risk with a treatment that is effective for serious diseases, particularly if existing treatment options are limited, and we factor this risk tolerance into our decision making.”

Novartis’ manufacturing issues

For the past year, Novartis has struggled with manufacturing problems at several plants around the world and attracted scrutiny from regulators. The latest mishap occurred in Rosia, Italy, where a data-handling discrepancy caused some vaccines to be temporarily and voluntarily held for several months. The drugmaker undertook a good manufacturing practice investigation and reported findings to the European Medicines Agency and the Agenxia Italiana del Farmaco before shipments resumed two months ago.

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“Novartis has struggled with manufacturing problems at several plants around the world and attracted scrutiny from regulators.”

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The disclosure came after a facility in Nebraska suffered embarrassing gaffes involving over-the-counter meds and animal health drugs. And the FDA sent a warning letter last November for “significant violations” at two other US plants – Broomfield, Colorado and Wilson, North Carolina. A Sandoz plant in Quebec, Canada, meanwhile, halted some production and there were problems at a facility in Austria.

Novartis is not the only drugmaker to experience such widespread problems. Over the past two years, the FDA, entered into a consent decree with Johnson &amp, Johnson, closely scrutinized numerous Hospira facilities, prompting Wall Street to speculate that consent decree is on its way, and issued a warning letter to Merck KGgA about problems at three plants – one that makes active pharmaceutical ingredients, another that makes finished prescription drugs and a third that is responsible for testing meds for the US market.

Whether Novartis is headed toward a consent decree is unclear. Despite the raft of serious problems other drugmakers have encountered, the FDA has not been quick to pursue such agreements, although the possibility, of course, always remains that the agency will consider such a step if manufacturing problems continue to appear systemic and intractable over a prolonged period.

Meanwhile, Novartis execs are clearly on the defensive and, as part of the damage control, Novartis ceo Joe Jimenez used a memo late last week to announce a new internal initiative. The drugmaker has already made several managerial changes at its over-the-counter division and recently begged veterinarians to stick with its products.

In a note late last week, he offered a progress report in which he repeatedly insisted that ‘quality matters’ and things are starting to look up. But the FDA has signaled a willingness to take a holistic approach to manufacturing reviews and such scrutiny can, of course, become costly. Whether such pep talks will amount to any significant change remains to be seen, but he is clearly worried that the string of problems has invited the sort of scrutiny that can reverberate for a long time.

J&amp,J settles marketing litigations

In an effort to resolve a mountain of litigation over the marketing of its antipsychotic medications, Johnson &amp, Johnson has agreed to pay $181 million to resolve claims by 36 states for promoting the Risperdal and Invega pills for unapproved uses. The settlement, which includes the District of Columbia, comes shortly before the healthcare giant is expected to pay as much as $2.2 billion over the same allegations by the feds involving these and other drugs.

The deal came after J&amp,J suffered setbacks in several states where off-label marketing charges went to court. In April, an Arkansas judge fined the healthcare giant $1 billion, just three months after J&amp,J agreed to settle a lawsuit brought by the Texas attorney general and just a few days of blistering courtroom testimony that placed its marketing practices in a harsh light.

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“…the healthcare giant is expected to pay as much as $2.2 billion over the same allegations…”

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And last year, J&amp,J was ordered by a South Carolina judge to pay $327 million for deceptive marketing, which he called detestable. Two years ago, a Louisiana jury ordered J&amp,J to pay $257.7 million in damages for making misleading safety claims, and $73 million in legal fees were later added.

However, the deal with the states includes provisions that are more specific than the sort of restrictions that the feds often impose on drug makers, such as agreeing not to misuse continuing medical education programs for marketing or awarding grants to doctors based on their prescribing habits. One provision, in particular, however, restricts the ability of drug makers to use sales and marketing personnel to distribute peer-reviewed reprints of journal articles that contain off-label information, which is a significant development.

“The J&amp,J / Janssen agreement goes part of the way toward addressing the government arguments in the First Amendment litigation about why off-label promotion should be prohibited entirely. FDA is saying they should be permitted to review claims before they are disseminated as off-label promotion. Janssen is saying we’ll meet you part of the way there. They’ll submit an application before they allow sales and marketing to disseminate peer review reprints. They’re at least implicitly acknowledging that justification has some merit.”

Arnie Friede, a former FDA associate chief counsel and a former senior corporate counsel at Pfizer.

Keller retires from Brown University

In the midst of an ongoing campaign to have a medical journal retract a controversial study of the Paxil antidepressant, the lead author, Martin Keller, quietly retired from his academic position at Brown University. Keller officially retired on June 30 and the next day was named an emeritus professor of psychiatry and human behavior, according to a university spokesman.

The spokesman, however, declined to provide any further information on the reasons for retirement and Keller did not respond to messages for comment. Consequently it is unclear if the move is linked to the hubbub surrounding the Paxil study, which has shone an uncomfortable spotlight on Brown University and figured in the recent $3 billion settlement paid by GlaxoSmithKline (GSK) to resolve civil and criminal charges in connection with off-label promotion of several drugs, failing to report safety data and reporting false prices. The deal was announced last month, after the retirement.

The saga began in 2001, when the Journal of the American Academy of Child and Adolescent Psychiatry published a paper concluding that Paxil was “generally well tolerated and effective for major depression in adolescents”. But the study has since been discredited amid charges that primary and secondary outcomes were conflated, selective results were reported and ghostwriting was involved.

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“…it is unclear if the move is linked to the hubbub surrounding the Paxil study…”

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The paper, though, has never been retracted and the universities whose academics were listed as co-authors did not rebuke the authors. Brown University, for instance, declined to take action concerning Keller. Late last year, a group of academics wrote university officials to seek a retraction, but were rebuffed by medical school dean Ed Wing, who wrote that the university would not contact the JACAAP to seek a retraction. The JACCAP editor later told BMJ the paper does not contain any inaccuracies and negative findings are included in a results table and, as a result, there are no grounds for withdrawal.

Oncologists more open to sales reps

Just as the pharmaceutical industry doubles down on researching cancer therapies, a new survey shows that oncologists are more likely than any other specialty to deny or restrict access to sales reps. The findings underscore the oft-stated impatience that many physicians have expressed with sales pitches and, simultaneously, a growing reliance on technology to gain info about treatments.

The survey found that 61 percent of oncologists placed moderate-to-severe restrictions on visits from reps, specifically, 11 percent cited severe restrictions and 50 percent impose restricted access. This makes oncology the most restrictive of the 20 most common medical specialties measured in the report by ZS Associates, a consulting firm that works with drugmakers on sales and promotional strategies.

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“…oncologists are more likely than any other specialty to deny or restrict access to sales reps.”

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Looked at another way, 39 percent of oncologists were accessible, compared with 65 percent of all prescribers. And just 9 percent of all prescribers placed severe restrictions on rep visits. Meanwhile, about 47 percent of cardiologists and only 38 percent of primary care physicians restrict rep access to the same degree. However, 52 percent of nephrologists ranked behind oncologists in overall restrictions.

Merck asks Supreme Court to review patent case

Last month, a US federal appeals court ruled that a pair of patent settlements between Merck’s Schering-Plough and two generic drug makers over the K-Dur blood pressure medication amounted to “evidence of an unreasonable restraint of trade”. The decision by the US Court of Appeals for the Third Circuit, which reversed a ruling by a federal court in New Jersey, was quickly hailed by the US Federal Trade Commission as proof that such deals are anti-competitive.

Now, Merck has asked the US Supreme Court to review the case, which the drugmaker argues is a perfect example of why the issue should be examined.

“This case presents one of the most significant unresolved legal questions currently affecting the pharmaceutical industry: what is the appropriate antitrust standard for evaluating settlements of patent litigation between brand manufacturers and generic manufacturers, where the settlement includes a payment from the brand manufacturer to the generic manufacturer?

“That question has been percolating in the lower courts for more than a decade. Until the decision in this case, the courts of appeals had consistently held that the federal antitrust laws generally permit a settlement that includes a payment from the brand manufacturer to the generic manufacturer, as long as the settlement does not exclude competition beyond the scope of the patent. The Third Circuit’s decision in this case dramatically departs from the prevailing view.”

Merck lawyers write in their brief.

Will the Supreme Court agree to review the case? This, of course, remains unclear, but given the split in the lower courts, the odds suggest this may happen. As the Merck lawyers write: “all of the interested parties — private plaintiffs, defendants, and the federal government — agreed that the issue presented is of enormous legal and practical significance”.

The next ‘Pharma news highlights’ will be published in October.

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About the author:

Ed Silverman is a prize-winning journalist who has covered the pharmaceutical industry for the past 16 years. In addition to editing Pharmalot, he is currently an editor-at-large for Med Ad News.

Previously, he was a bureau chief for The Pink Sheet, the venerable industry newsletter, and a contributor to its sister publication, In Vivo magazine. Before that, Silverman worked as a business writer for The Star-Ledger of New Jersey, one of the nation’s largest daily newspapers, where he conceived and launched Pharmalot. During his 13-year tenure, he closely followed a variety of topics of concern to those who work for, and with, drug makers – drug development, mergers and acquisitions, regulatory oversight, safety and pricing controversies, and marketing issues.

Prior to joining The Star-Ledger, Silverman spent six years at New York Newsday and previously worked at Investor’s Business Daily, among other newspapers. He has a master’s degree in journalism from New York University and a bachelor’s degree in accounting from Binghamton University. Tethered to his laptop and Blackberry, Silverman lives in suburban New Jersey with his wife, three children, a sizeable Labrador retriever and a sneaky beagle.

Which pharma news story has got you talking this month?