Amgen latest drugmaker with Herceptin biosimilar sidelined by FDA letter

Amgen, in a two-sentence announcement today, said it received a complete response letter for the biosimilar of Roche’s cancer med Herceptin it developed with Allergan. It marks the third Herceptin biosimilar that has been stalled by the FDA but has won approval in Europe.

The Thousand Oaks, California-based drugmaker offered no insight into what the FDA found lacking in its version. “We will work closely with the FDA to bring this important medicine to patients in the U.S. We do not expect this to impact our U.S launch plan,” it said in the announcement.

Biosimilar makers have been hot to develop their own versions of Roche’s Herceptin, a long-in-the tooth oncology drug that still raked in $2.5 billion in U.S. sales last year and $7 billion worldwide. Mylan and partner Biocon, Pfizer and now Amgen have all had their initial applications rejected by U.S. regulators. Pfizer just today won an European Medicines Agency approval for its Trazimera.

None of the drugmakers have provided much detail as to what triggered their CRLs, so it is unknown whether there has been a common theme for the denials or what the hangup is for the FDA that has not bothered the EMA. FDA concerns about Biocon’s Indian plant figured into the rejection of the version from Mylan and its Indian partner.

Mylan and Biocon won an FDA thumbs-up for their Herceptin biosimilar in December, but only after a three-month delay in which the FDA looked over some new technical data that had resulted from changes made in their manufacturing operations. When the partners got their CRL it looked like they would go from the front of the line to the back of the line as the FDA considered applications from other drugmakers. But the partners ended up being the first to win approval as competitors also had their versions sidelined.

These delays have allowed Roche to continue to go to the Herceptin cash machine. Despite recent approvals for biosimilars in the EU, Herceptin sales worldwide were up 3% last year to about $7 billion on higher sales in the U.S. and Brazil. While most of those sales come from the U.S., $2.7 billion, EU revenue is also significant, at $2.1 billion.

While regulatory and manufacturing stumbles have protected Roche’s Herceptin sales, the Swiss drugmaker is also throwing up roadblocks. Last fall, Roche sued Pfizer for infringement on 40 Herceptin patents, asking a court to block a potential biosim launch. Pfizer said it will defend its “position vigorously and in the appropriate venue.”

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Medtronic recalls HeartWare HVAD over electrical disconnection

Medtronic is recalling the HeartWare HVAD because of the possibility for an interruption to occur in the electrical connection between the system’s power source and the HVAD controller, the FDA said in a statement on its website. The agency added, “Interruptions to the electrical connection could cause unintended intermittent electrical disconnection, which could result in a pump stop. A pump stop could cause patient harm such as exacerbation of heart failure symptoms, or symptoms such as mild weakness, dizziness, anxiety, nausea, loss of consciousness, or death.”

https://bit.ly/2JkqlHT

Theranos investors cannot pursue class action: U.S. judge

A U.S. judge has ruled that investors who claimed that Theranos Inc defrauded them into investing indirectly in the company by touting revolutionary blood-testing technology that never existed cannot pursue their claims as a class action.

The ruling late on Thursday by U.S. Magistrate Judge Nathanael Cousins in San Jose, California, is a setback for investors who might otherwise recover more by suing Theranos, Chief Executive Elizabeth Holmes and former Chief Operating Officer Ramesh “Sunny” Balwani as a group.

The proposed class had included more than 200 people who invested in funds between July 29, 2013, and Oct. 5, 2016 for the purpose of buying shares in Theranos, once a star of Silicon Valley.

Cousins, however, said individual lawsuits were appropriate because some investors might be unable to show they relied on the blood-testing company’s alleged misrepresentations.

“It is easy to imagine, for example, that someone invested simply because a friend suggested it, or because all that percolated down the grapevine was vague insight that Theranos was a fast-growing company, or had promising (but unspecified) technology,” Cousins wrote in a 34-page order.

Reed Kathrein, a lawyer for the plaintiffs, said he may appeal or seek reconsideration.

“It is too early to say anything other than we are very disappointed,” ahead of the scheduled depositions of Holmes and Balwani and completion of discovery this month, Kathrein said in an email.

Indirect investors in private companies such as Theranos cannot sue under federal securities laws, which address the integrity of public markets. The Theranos investors sought to avoid this by suing under California state law.

Michael Mugmon, a lawyer for Theranos, said: “We are pleased by the court’s ruling, as it brings the company a step closer to resolving its outstanding legal issues.”

Lawyers for Holmes and Balwani did not immediately respond to requests for comment.

Once valued at $9 billion, Theranos’ fortunes darkened amid reports that its technology, which offered hope that one drop of blood could help Americans control their health, did not work.

On March 14, the U.S. Securities and Exchange Commission charged Theranos, Holmes and Balwani with running a “massive fraud” by exaggerating the technology while raising more than $700 million from investors.

Holmes settled by agreeing to cede majority control, pay a $500,000 fine, and not serve as an officer or director of public companies for 10 years. Balwani did not settle.

Theranos also faces a criminal probe into whether it misled investors, The Wall Street Journal said in April.

The case is Colman et al v Theranos Inc et al, U.S. District Court, Northern District of California, No. 16-06822.

https://reut.rs/2JgMC9B

ASCO stand on Trump drug price proposals

A leading U.S. group of cancer doctors is wary of new Trump administration proposals for lowering drug prices, particularly if new negotiation tools are introduced that will mean the U.S. government no longer routinely pays for all cancer drugs in the Medicare health program for older people.

The rising cost of cancer care will be in focus during an annual meeting of the American Society of Clinical Oncology (ASCO) that begins Friday in Chicago. In recent years, potent new immunotherapies and treatments that target genetic mutations underlying cancer have successfully curbed the disease in some patients.

But they have come with ever-rising price tags, spurring new questions about how much individuals, corporations and the government in the United States, already the world’s most expensive health system, will pay for these breakthroughs.

President Donald Trump last month unveiled a “blueprint” to reduce drug prices by promoting the entry of cheaper rivals to existing drugs and giving private insurers more scope to negotiate prices.

In private health insurance plans, insurers have tools to negotiate prices on the drugs they cover for their members. In exchange for manufacturer discounts, insurers may lower the patient co-payment below competing treatments, or drop coverage of a rival drug altogether, to increase prescriptions.

The Trump proposal includes the possibility that the government would stop covering all approved drugs for certain illnesses, including cancer, in the Medicare program. It has requested feedback from the industry on this and other ideas.

“It is a balancing act, because we do think that there should be an ability to negotiate price, but we are always driven by our belief that patients should not be denied the most effective drugs for their condition,” ASCO’s chief executive officer, Dr. Clifford Hudis, told Reuters.

Another idea is to change Medicare’s reimbursement of doctors including a fee calculated as a percentage of a drug’s price. Critics say the payments encourages physicians to use the most expensive drugs. Hudis said ASCO is not opposed to changing the formula, but argues that oncology practices will still need to be reimbursed for handling specialized cancer medicines delivered by infusion or injection.

ASCO, the nation’s leading association of cancer physicians, said it will publicize its full response after submitting feedback to the Trump administration by a July 16 deadline.

EFFECTIVENESS VS PRICE

U.S. spending on cancer drugs reached almost $50 billion last year – nearly doubling since 2012 – and is projected to double again to $100 billion in five years, according to IQVIA, which collects drug sales data.

Expensive new cancer treatments like Merck & Co’s $162,000-per-year immunotherapy Keytruda and Gilead Sciences Inc’s $373,000 blood cancer therapy Yescarta, which have helped some patients survive previously untreatable disease, are contributing to the increase.

But so are less effective drugs without competitors whose prices are raised by manufacturers each year. Oncologists and other specialists benefit from price increases on drugs that are administered in their offices.

Without percentage-based fees, oncology practices would lose “their ability to make considerable sums off their relationship with the pharmaceutical industry,” said Dr. Peter Bach, director of Memorial Sloan Kettering’s Center for Health Policy Outcomes in New York. ASCO and other institutions have proposed their own methods for reducing healthcare costs, but stopped short of urging drugmakers to lower prices. ASCO has recommended ranking drugs on their comparative clinical value, including relative efficacy and side effects, but not price. The group has also suggested that the price of a cancer drug could vary depending on how effective it is for a specific indication, or how well an individual patient fares after the treatment.

The association does not support moving to a flat fee for treating cancer patients, including drugs, an approach that is being used in other specialties. That “could force providers to make suboptimal or lower-value choices,” the organization said. At ASCO’s annual meeting, which runs from June 1-5, cancer researchers will provide new data on survival rates with Keytruda, on the emerging class of CAR-T cell treatments for blood cancers and on genetically targeted therapies.

Some research will address the cost question, including a comparison of treatment costs and outcomes for colon cancer patients in the United States and Canada.

https://reut.rs/2LegmB5

Euro regulators recommend restrictions on Merck, Roche immunotherapies

The European Medicines Agency on Friday recommended restricting use of two immunotherapies, one from Roche and the other from Merck, in initial bladder cancer treatment, saying they may not work as well as chemotherapy in some patients.

“Early data from two clinical trials show reduced survival with (Merck’s) Keytruda and (Roche’s) Tecentriq when used as first-line treatments for urothelial cancer in patients with low levels of a protein called PD-L1,” the agency said. “The data indicate that Keytruda and Tecentriq may not work as well as chemotherapy medicines in this group of patients.”

https://reut.rs/2snWFzO

Roche gets Euro OK for breast cancer med-chemo combo therapy

Roche announced that the European Commission has approved Perjeta in combination with Herceptin and chemotherapy for post-surgery treatment of adult patients with HER2-positive early breast cancer at high risk of recurrence. High risk of recurrence is defined as lymph node-positive or hormone receptor-negative disease. The Perjeta-based regimen should be administered for a total of one year as part of a complete regimen for eBC and regardless of the timing of surgery. “Despite advances in the treatment of HER2-positive early breast cancer, many people still have a recurrence and progress to an incurable stage. In the early breast cancer setting, where the ultimate goal is cure, it is critical that we continue building on existing therapies,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “Today’s approval is great news, as we believe the Perjeta-based regimen has the potential to make a significant impact on the lives of people with HER2-positive early breast cancer who are at high risk of recurrence. We are committed to working with EU member states to ensure the Perjeta-based regimen is available to eligible patients as soon as possible.”

https://bit.ly/2J1MNpH

Estrogen, T cell immune response linked to autoimmune inflammation

Women are more prone to the development of autoimmune diseases. The female hormone estrogen is likely to affect the immune system. A team of scientists from Turku Center for Biotechnology and University of Georgia reported new findings related to the involvement of estrogen hormone receptor in autoimmune diseases.

The incidence of autoimmune diseases such as MS, RA, and SLE is higher in women than in men. The estrogen hormone secreted in women may contribute to the pathogenesis of these diseases. A research team led by Docent Zhi Chen from Turku Center for Biotechnology of the University of Turku has collaborated with researchers from the University of Georgia, United States to address the long-standing issue of hormonal effect on autoimmune diseases.

Estrogen hormone shows its action on cells mostly through estrogen receptor alpha (ERα). Researchers from Turku generated mice with ERα protein specifically deleted in T cells.

“The eureka moment of our research is that in a mouse model of human inflammatory bowel disease, transfer of naive T helper cells from ERα deficient mice did not succumb to colitis, unlike transfer from their counterparts,” Docent Zhi Chen says.

“Furthermore, using cutting-edge technique RNA sequencing approach combined with in vitro and in vivo experiments, we discovered that ERα regulates multiple aspects of T cell function, including T cell activation, proliferation and survival,” Chen adds.

Regulatory T cells are group of T cells that help in preventing autoimmune diseases. The researchers found that ERα influences the function and differentiation of regulatory T cells.

More information: Imran Mohammad et al, Estrogen receptor α contributes to T cell–mediated autoimmune inflammation by promoting T cell activation and proliferation, Science Signaling (2018). DOI: 10.1126/scisignal.aap9415

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