With a number of COVID-19 variants raising concerns, the FDA said it’s working on guidances to help sponsors evaluate the impact of the mutations as they develop diagnostics, drugs and vaccines targeting the coronavirus.

“We believe these guidances will demonstrate our flexibility to work with individual sponsors to support their modification or development of products to fight COVID-19,” Acting FDA Commissioner Janet Woodcock said.

In the drug space, Woodcock said the FDA is working with sponsors to accelerate the evaluation of new antibodies that could be effective against mutations, as some of the neutralizing monoclonal antibodies that have received emergency use authorization (EUA) or are under development are less effective against some of the variants that have emerged.

Woodcock also acknowledged that the performance of diagnostics could be adversely impacted by the variants, although she said, “at this time, we believe the risk that the currently known mutations will impact overall testing accuracy of molecular tests is low.”

But going forward, the agency is considering expanding in silico monitoring by sponsors before and following authorization to assess for mutations that impact a test’s performance, test designs to minimize the impact of new mutations and transparent labeling about what a test can detect.

While the data available so far suggest that the two vaccines authorized by the FDA remain effective against the currently circulating variants, Woodcock said the agency is considering the types of data that will be needed to support changes in a vaccine as variants continue to emerge. Part of that discussion involves how sponsors could demonstrate an immune response to new variants through streamlined clinical programs that can be executed quickly while gathering the data the FDA will need to evaluate effectiveness.

In addition to the guidances, Woodcock said the FDA is conducting scenario planning to help “anticipate and address impacts to products and supply chains as quickly as possible, no matter what path the pandemic takes in the next months.”

Meanwhile, the FDA has revised the EUA it issued last August for convalescent plasma to clarify that the authorization is limited to the use of only high titer COVID-19 convalescent plasma in hospitalized patients early in the course of disease and those hospitalized with impaired humoral immunity. The revised EUA also includes several more tests that are acceptable for qualifying high titer COVID-19 convalescent plasma.

The revision is based on data from additional studies that show the potential clinical benefit is associated with high titer units administered early in the course of disease. “Transfusion of COVID-19 convalescent plasma in hospitalized patients late in the course of illness . . . has not been associated with clinical benefit,” the FDA said.

CBO model touts savings of H.R. 3

Based on a simulated model of drug pricing negotiations, the U.S. Congressional Budget Office (CBO) said last week that direct Medicare negotiations, as would be required under H.R. 3, would reduce U.S. drug prices by 57% to 75%, with the variance depending on the data and parameters it used in its calculations.

In the CBO analysis, the average drug price resulting from such negotiations would be about 120% of an international drug price index – the ceiling price allowed under H.R. 3.

Unlike a CBO estimate issued after H.R. 3 was first proposed in 2019, the new report focuses on the model and its projected savings. It is silent on the impact negotiations could have on innovation. In its 2019 estimate, the CBO said the negotiations mandated by H.R. 3 could produce savings of up to $345 billion from 2023 through 2029, but the long-term impact likely would be a reduction in biopharma R&D and eight to 15 fewer new drugs being developed.

When the legislation was being discussed in committee in 2019, Democrats said the predicted savings was worth the sacrifice of 15 new drugs. That was before COVID-19 when drug and vaccine innovation became a matter of survival for hundreds of thousands of people.

The House passed H.R. 3 on party lines in 2019, but the legislation went nowhere in the Republican-controlled Senate. Although the bill would have to be reintroduced in the House, it could make headway in the 117th Congress through the reconciliation process now that Democrats have narrow control of the Senate.

FDA to ODAC: Are data ripe for 2nd TNBC Keytruda approval?

The FDA’s Oncologic Drugs Advisory Committee (ODAC) will be faced with one question when it meets Feb. 9 to consider yet another indication for Merck & Co. Inc.’s Keytruda (pembrolizumab).

That question is whether the data are there yet for an approval decision on the use of Keytruda in high-risk, early stage triple-negative breast cancer (TNBC) or whether the FDA should delay that decision until it gets more data from a future analysis of the KEYNOTE-522 trial.

The specific proposed indication is to use Keytruda in combination with multi-agent chemotherapy for neoadjuvant treatment followed by Keytruda monotherapy for adjuvant treatment in high-risk, early stage TNBC. Since many patients with that type of TNBC may be cured with standard therapy, the FDA said the added toxicity of pembrolizumab for neoadjuvant and adjuvant treatment must be carefully considered.

In its briefing document for the meeting, the FDA noted that only a small absolute improvement in pCR rate was observed in neoadjuvant treatment with pembrolizumab. It said it didn’t view that small rate difference between treatment arms as clinically meaningful, adding that the interim analyses may have overestimated the treatment effect, given the small number of events. FDA reviewers also characterized the event-free survival and overall survival data as “immature and unreliable.”

First approved in 2014 as an orphan drug for use in patients with advanced or unresectable melanoma who are no longer responding to other drugs, the PD-1 inhibitor is now approved to treat nearly 20 different cancers, including, in combination with chemotherapy, locally recurrent unresectable or metastatic TNBC with tumors expressing PD-L1.

Fifth Circuit reiterates no liability remedy for generics

In a ruling upholding a lower court’s dismissal of a liability suit against Novartis Pharmaceuticals Corp. and several generic drug companies, the U.S. Court of Appeals for the Fifth Circuit recognized that Supreme Court case law left the plaintiff, Ramon Johnson, without a legal remedy for injuries he allegedly suffered because he took generic versions of the antibiotics Minocin (minocycline) and Tegretol (carbamazepine).

Johnson, who claimed he developed symptoms of Peyronie’s disease (PD) after taking minocycline and a worsening of the symptoms when he later was prescribed carbamazepine, tried to get around the Supreme Court’s Mensing and Bartlett rulings preempting state liability claims by saying his was a “strict liability marketing defect claim” under Texas law.

His argument failed, the Fifth Circuit said, as it basically was the same one presented under Mensing. To comply with the state law, the generic companies would have had to update their label when they acquired knowledge of a risk of PD from their generics, but that would have been impossible under federal law, the Supreme Court said in its preemption finding in Mensing.

The Fifth Circuit, holding to its own precedent, also shot down Johnson’s claims against the brand company. Under Texas law, brand drug companies can only be held liable for the products they make and they “owe no common-law duty under Texas law” to those who take generic versions of their drugs, the appeals court reminded Johnson.

Johnson also tried to argue that the companies perpetrated fraud on the FDA, but the court said that argument would only make a difference had Johnson taken the brand drug.

Consultant faces insider trading charges

Mark Ahn, an Oregon-based biotech consultant, was charged with two counts of securities fraud Feb. 5 in federal court in Boston in connection with an insider trading scheme involving Ultragenyx Pharmaceutical Inc.’s $138 million acquisition of Cambridge, Mass.-based Dimension Therapeutics Inc. in 2017.

In the course of his consulting work for a New York firm looking to acquire Dimension, Ahn learned of Dimension’s intention to be acquired by another biotech and gained access to confidential information about Dimension’s business, according to the U.S. Attorney’s Office for the District of Massachusetts. While in possession of the nonpublic information, Ahn bought Dimension stock, which increased 262% in one day when Dimension announced that its acquisition by Ultragenyx, of Novato, Calif.

If found guilty, Ahn could face up to 25 years in prison and a fine of $250,000. Ahn also faces a separate civil action filed Feb. 5 by the SEC. The SEC is seeking penalties, injunctive relief and an order barring Ahn from serving as an officer or director of any SEC-reporting company.