Johnson & Johnson (J&J) and its U.S.-based Janssen pharmaceutical companies will contribute up to an additional $1 billion in a settlement to resolve all opioid lawsuits filed, as well as future claims, by states, cities, counties and tribal governments.

The New Brunswick, N.J.-based company last year agreed, in principle, to pay $4 billion to resolve hundreds of opioid suits in several states, including a federal multidistrict litigation that combines more than 1,600 cases brought by states, counties, cities, tribes and other groups against J&J and other opioid manufacturers.

The additional $1 billion J&J offered this week stems from continued negotiations and is intended to maximize participation in that settlement, the company said Oct. 13. The terms and conditions of the settlement are still being finalized, but it includes no admission of liability or wrongdoing.

J&J signed onto the agreement shortly after an Oklahoma judge ordered it last year to pay more than $572 million to immediately abate the nuisance he said the company and its subsidiary had caused in the state with its “misleading marketing and promotion” of opioids. The judge later reduced the amount to $465 million, citing an error he had made in his calculations.

(J&J was one of three biopharma companies charged with being a public nuisance in Oklahoma due to their marketing of FDA-approved opioids. The other two, Purdue Pharma LP and Teva Pharmaceutical Industries Ltd., settled before the trial began.)

J&J is appealing the Oklahoma decision and said it will continue to defend against any opioid-related litigation not resolved by the final agreement.

Retiring lawmakers urge 340B modernization

In what could be their swan song before retiring from the U.S. Congress, Rep. Greg Walden (R-Ore.), ranking member of the House Energy and Commerce Committee, and Sen. Lamar Alexander (R-Tenn.), chair of the Senate Health, Education, Labor and Pensions Committee, are asking for ideas on how to improve the 340B Drug Pricing Program that gives qualifying hospitals steep discounts on certain prescription drugs to generate revenue for “charity” services.

They also stressed that Congress and 340B participants must be open to updating the program so it can best serve seniors and the most vulnerable patients while still protecting services provided by participating hospitals, clinics and other health care providers. While there is strong bipartisan support for 340B in Congress, lawmakers have been divided on the need for modernization and stronger oversight efforts.

Walden and Alexander noted that changes are “long overdue” to the nearly 30-year-old program, pointing to “significant confusion about the requirements of the program and the lack of data necessary for effective oversight.”

For too long, 340B has been governed by guidance and regulatory actions rather than law, Walden and Alexander said. Consequently, the Health Resources and Services Administration (HRSA), which is tasked with overseeing the program, has limited enforcement ability. Because of resources that haven’t kept up with the growth of the program, HRSA relies primarily on hospital self-attestations of eligibility.

Since 2005, the number of hospitals and associated sites participating in 340B has increased nearly 3,000% – from 432 hospitals and 594 associated sites in 2005 to 2,541 hospitals and 26,641 associated sites today.

There’s also been significant growth in the number of contract pharmacies involved in the program. Although the pharmacies aren’t referenced in law, from 1996 to 2010, participating hospitals and clinics with no in-house pharmacy were allowed to contract with one outside pharmacy to ensure patients could access the discounted drugs – even though they’re not required to pass the discounts on to the patient. That cap was lifted in 2010, so now participating hospitals and clinics can contract with unlimited outside pharmacies. As a result, the number of contract pharmacies involved in 340B has grown from 1,300 at the beginning of 2010 to more than 25,000 today.

Because of that expansion, some drug manufacturers recently have taken it upon themselves to limit contract pharmacy involvement in 340B by demanding data claims or refusing to extend the mandated discounts to the pharmacies.

“We have been following this activity closely and believe contract pharmacies are an important part of the continued discussion around 340B modernization,” Walden and Alexander said.

“Allowing program participants to continue playing by their own rules leaves the most important 340B stakeholder on the sideline – the patient,” the lawmakers said.

How human are ‘human antibodies’?

In a precedential opinion that boiled down to the definition of “human antibodies” and the standard used to interpret claims related to those antibodies, the U.S. Court of Appeals for the Federal Circuit upheld the Patent Trial and Appeal Board’s (PTAB) inter partes review (IPR) decision that invalidated Immunex Corp.’s ’487 patent, which covers isolated human antibodies that bind the human interleukin-4 receptor – a significant inhibition in treating various inflammatory disorders.

Immunex’s claims had held up in a federal district court where a narrower, or Phillips, standard of interpretation was used. But in a subsequent IPR filed by Sanofi SA, Genzyme Corp. and Regeneron Pharmaceuticals Inc., the PTAB’s broadest reasonable interpretation (BRI) standard opened the definition to include partially human and humanized antibodies, which were subject to prior art that made the claims obvious.

Although the PTAB has since adopted the court’s narrower interpretation standard for IPRs, the Federal Circuit said it still must use the BRI in appeals dealing with IPRs filed when that was the PTAB standard for unexpired patents.

After the briefs were submitted in the appeal of the PTAB decision, Immunex filed a terminal disclaimer of the patent. As a result, the patent expired May 26, 2020 – a few months before oral argument in the Federal Circuit.

Immunex argued that since the patent had expired, the Federal Circuit should revert to the Phillips standard, which it has used in other cases involving expired patents. The Federal Circuit declined, saying the expiration was expected in those cases and it happened before briefing began, so all the parties could brief accordingly.

That’s “not so here, where the patentee shortened the term abruptly after the parties had already fully briefed claim construction under the BRI standard,” according to the Federal Circuit opinion that was handed down Oct. 13. Thus, the court reviewed the PTAB’s claim construction by giving the terms of the claim their “broadest reasonable construction in light of the specification of the patent.”

Even if the Federal Circuit had used the narrower Phillips standard, the wording of the claims themselves – and Immunex’s revisions to the patent – argued against “human antibodies” being defined as only those that are fully human. “Nothing in the claim’s language restricts ‘human antibodies’ to those that are fully human,” the Federal Circuit said. It cited claim specifications that made it “clear that ‘human antibodies’ is a broad category encompassing both partially and completely human antibodies.”

The appellate court also referenced an amendment Immunex made to the patent in which it removed a claim covering “humanized and chimeric embodiments as well as fully human ones,” replacing it with the term “human antibodies.” In a post-amendment office action, the patent examiner “wrote that the amended ‘human’ antibodies encompassed ‘humanized’ antibodies,” the court said.

Immunex said, with no substantiation, that the examiner’s note was a copy and paste error. However, the court noted that “Immunex made no effort to disabuse the examiner of this understanding.”

ANDA suitability MAPP updated

The FDA revised its manual of policies and procedures (MAPP) for ANDA suitability petitions to reflect and clarify its current policies and procedures.

A prospective applicant may submit a petition requesting permission to submit an abbreviated new drug application (ANDA) for a generic that differs from a reference listed drug in its route of administration, dosage form or strength, or that has a different active ingredient in a fixed-combination drug product.

The agency will reject suitability petitions if:

  • it determines the safety and effectiveness of the proposed change cannot be adequately evaluated without data from investigations that would be beyond the scope of what may be required for an ANDA;
  • a drug is approved in a new drug application for the change requested in the suitability petition;
  • the petition requests changes that trigger the need for pediatric studies under the Pediatric Research Equity Act.

MHRA: Drug interactions possible with COVID-19

The U.K.’s Medicines and Healthcare products Regulatory Agency (MHRA) issued guidance Oct. 13 reminding of the need to continue regular blood tests in patients taking warfarin and other anticoagulants who have developed symptoms or tested positive for COVID-19.

The guidance also includes a reminder of the potential for drug interactions between some anticoagulant tablets and drugs, such as antivirals or antibiotics, used to treat infections. The interactions may increase the blood-thinning effect of some anticoagulants and lead to a higher risk of bleeding, according to the MHRA.

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