– Recommendation based on the results of IMpassion130 study in triple-negative breast cancer, an aggressive type of breast cancer with high unmet medical need
– First positive Phase III cancer immunotherapy study for people with metastatic triple-negative breast cancer
Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Tecentriq® (atezolizumab) plus chemotherapy (Abraxane®; nab-paclitaxel) for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumours have PD-L1 expression (>= 1%) and who have not received prior chemotherapy for metastatic disease.
“This CHMP recommendation marks a breakthrough in the treatment of triple-negative breast cancer, an aggressive type of breast cancer with high unmet medical need,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “With today’s announcement, we hope that people living with PD-L1-positive metastatic triple-negative breast cancer in Europe will soon have a new treatment option with the Tecentriq combination.”
The CHMP recommendation is based on data from the Phase III IMpassion130 study, which demonstrated that Tecentriq plus nab-paclitaxel significantly reduced the risk of disease worsening or death (progression-free survival; PFS) by 38% compared with nab-paclitaxel alone (median PFS=7.5 vs 5 months; HR=0.62, 95% CI: 0.49-0.78, p
After two decades of keeping the public in the dark about millions of medical device malfunctions and injuries, the Food and Drug Administration has published the once-hidden database online, revealing 5.7 million incidents publicly for the first time.
The newfound transparency follows a Kaiser Health News investigation that revealed device manufacturers, for the past two decades, had been sending reports of injuries or malfunctions to the little-known database, bypassing the public FDA database that’s pored over by doctors, researchers and patients. Millions of reports, related to everything from breast implants to surgical staplers, were sent to the agency as “alternative summary” reports instead.
Here’s what we found in those newly public reports:
Almost all the products were made by LifeScan, which had been a Johnson & Johnson company until it was sold to a private equity firm in 2018. Common problems included displaying incorrect messages, losing power or being damaged before customers started using them, according to the database.
“When you’re trying to manage a chronic disease, and especially if your numbers are dangerously high, that’s life-threatening,” said Linda Radach, who chairs the medical device committee for the Patient Safety Action Network.
LifeScan did not return requests for comment.
The FDA said the number of glucose meter problems in the alternative summary reporting database shouldn’t be a surprise.
“Approximately 10% of the U.S. population has diabetes and most rely on these devices several times a day,” said FDA spokesman Michael Felberbaum. The agency also sees a “high volume” of adverse events for glucose meters in its longtime public database, called MAUDE, he said.
He reiterated that the alternative summary reporting program was intended for “well-understood” adverse events “so that we could focus more resources on identifying and taking action on new safety signals and less understood risks.”
2. There were 2.1 million reports for bad dental implants. And 114,200 were reported last year.
This kind of implant goes into the bone to support an artificial tooth or implant. Many of the reports were for problems with connections between the device and the bone.
“A lot of people have gone out and gotten these and probably don’t know about these risks,” said Madris Tomes, a former FDA manager who now runs a website to make the notoriously clunky MAUDE easier to work with.
Dental implants were among the last device types to lose permission to report harm via alternative summary reports instead of the public database. Although the device harm data doesn’t include what happened to patients, Tomes said that if a dental implant has to be removed, it often can’t be replaced because the underlying bone is so damaged.
Felberbaum said that the high number of reports for dental implants is expected because these are commonly used devices, and that more companies have brought new products to market in the past two decades.
3. There were 176 deaths reported through the alternative summary reporting system.
Alternative summary reports are not supposed to include deaths, except for cardiac arrest potentially caused by certain kinds of heart valves that were implanted at least five years beforehand. Those accounted for two-thirds of the deaths in the hidden database, KHN found.
The most recent death was reported last fall by Medtronic, and it was related to a MiniMed Paradigm insulin pump that was hard to program or calibrate. Deaths reported to the once-hidden database also included fatalities associated with two kinds of pacemakers, a breast implant, an intra-aortic balloon pump and a ventilator.
When asked why these were there, the FDA said its “standard practice” was to reach out to the manufacturer for more information when it detected an “ineligible event” in the alternative summary reports. Sometimes, a death was reported in error. Sometimes, the FDA required the manufacturer to report an incident to the public database as well.
KHN found that of the 59 ineligible deaths, only eight appeared to be revised in updated alternative summary reports.
“In some cases, the FDA revoked ASR exemptions following continued reporting of ineligible events in ASRs,” said Felberbaum, adding that ineligible deaths represented “0.001% of all reports received through the ASR program.”
The FDA contacted Medtronic “a number of weeks ago” about the 2018 insulin pump death, said company spokeswoman Pamela Reese. The death was not reported to MAUDE because the “alleged” device malfunction “did not cause or contribute to the patient death,” she said, adding that it was actually caused by “stroke and pneumonia.” She said that the company was in compliance with reporting rules and that the FDA has not asked Medtronic any additional questions about it.
“One has to wonder what other information wasn’t made public if something that clear-cut [the instruction not to include deaths in the ASR] was included and hidden from the public,” said Diana Zuckerman, president of the nonprofit National Center for Health Research. “Did FDA notice?”
4. Surgical stapler-related malfunctions accounted for more than 66,000 previously hidden incidents since 2001.
The KHN investigation spotlighted problems with staplers, which tend to be used in minimally invasive surgery to cut and seal tissue and vessels quickly. Although the FDA received only 84 reports for stapler-related harm in the public database, it acknowledged earlier this year that it had received nearly 10,000 reports through alternative summary reporting.
The most common problems were staplers that failed to fire or fired malformed staples. Nearly 4,700 stapler problems were reported through the hidden database in 2017 alone. If a stapler fails to seal tissue properly during surgery, it can lead to serious bleeding or infection.
An FDA advisory panel last month recommended the agency switch staplers to a higher-risk classification with more safety requirements.
5. Breast implant injuries and malfunctions accounted for nearly half a million unique reports over two decades, including implants that leaked, deflated or migrated.
More than 6,600 incidents have been reported in 2019 by three companies: Allergan, Mentor and Sientra. The most common problem was rupture.
Tomes was especially concerned about cancer attributed to breast implants, which was the subject of an investigation by the International Consortium of Investigative Journalists last fall. But without publicly available data tracking patient problems, which exists in adverse events data for drugs but not devices, it’s impossible to say.
“How is the public supposed to make sense of this if they’ve redacted patient safety codes?” she asked.
Plus: Thousands of medical device types are still eligible for reporting outside the FDA’s public database.
There are still ways that device makers can avoid submitting individual injuries and malfunctions to the MAUDE database.
To replace the ASR program, the FDA has launched the Voluntary Summary Reporting Program. More than 5,600 device types—or 87% of them—are eligible for summary reporting of device malfunctions, according to FDA records.
Patient advocates say they fear that these will be just as difficult to tally and track as ASRs. For example, a summary report for 156 injuries would appear to be a single MAUDE report with a note that it represents 156 injuries, not one.
“Why would you end one [hidden data program] just to start another?” Radach asked.
Methodology: To avoid double-counting adverse events, KHN counted each event identified with a unique report ID only once, unless otherwise noted. Although this isn’t the norm, some companies appear to have recycled report IDs, using them for more than one event. As a result, our counts may be underestimated.
The Mountain View, CA-based develops solutions for patients with chronic diseases that leverage technology and data science. It began with a focus on diabetes, but now has offerings for hypertension, prediabetes and weight management and behavioral health.
Its diabetes solution includes a cellular-connected interactive blood glucose meter, an unlimited supply of test strips, personalized Health Nudges to support behavioral change, various digital tools and coaching/monitoring services.
It says its clients are employers, health plans, government entities and labor unions. It has a subscription-based revenue model which typically run 1-3 years.
Thermo Fisher Scientific (TMO-1.4%) is down, albeit on light volume, in apparent response to a two-day customer disruption caused by a fire at a Pittsburgh, PA data center.
Customers were able to purchase products from its Life Technologies unit but not from Fisher Scientific.
Sarepta Therapeutics (SRPT+19.4%) is up more than double normal as investors buy in after Pfizer’s (PFE) data presentation this morning on DMD gene therapy candidate PF-06939926. Apparently, interim data from a small Phase 1 study was on par with Sarepta’s AAVrh74.
Lannett Company, Inc. (NYSE: LCI) today announced that it has entered into a three-year agreement with Elite Pharmaceuticals to be the exclusive U.S. distributor of a Dantrolene Capsules 25 mg, 50 mg and 100 mg. Total U.S. sales of Dantrolene Capsules 25 mg, 50 mg and 100 mg was approximately $6.4 million for the 12 months ended April 2019, according to IQVIA, although actual generic market values are expected to be lower.
“We have commenced the distribution of Dantrolene, for which the market is currently comprised of a small number of competitors,” said Tim Crew, chief executive officer of Lannett. “While the sales potential for this product is modest, adding Dantrolene to our portfolio demonstrates our commitment to our customers and patients, as well as our success in expanding relationships with existing strategic partners. This is our second transaction with Elite.”
Under the agreement, Lannett will primarily provide sales, marketing and distribution support for the product, for which it will receive a share of the profits. Other financial terms were not disclosed.
Dantrolene Capsules 25 mg, 50 mg and 100 mg is the therapeutic equivalent to the reference listed drug, Dantrium® Capsules 25 mg, 50 mg and 100 mg of Par Pharmaceuticals, Inc. (an Endo International Company).
Aimmune Therapeutics, Inc. (Nasdaq: AIMT), a biopharmaceutical company developing treatments for life-threatening food allergies, today announced that it has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for AR101, an investigational biologic oral immunotherapy to reduce the frequency and severity of allergic reactions following exposure to peanuts in children and adolescents ages 4 to 17.
“This is an important milestone for us as a company, as well as for people across Europe living with peanut allergy, a growing worldwide health problem that significantly affects the quality of life of both patients and their families,” said Jayson Dallas, M.D., President and Chief Executive Officer of Aimmune. “We are continuing to expand our organization across Europe to prepare for potential approval of AR101 in key markets and engaging in reimbursement discussions to expedite access for patients upon approval.”
The MAA submission includes extensive data from the only Phase 3 clinical trial program to meet the primary endpoints in children and teens with peanut allergy. This program included well over 1,000 patients enrolled into the PALISADE, RAMSES and ARTEMIS trials. The pivotal European Phase 3 ARTEMIS study, which represents a key component of the MAA submission, reinforced the consistent clinical profile of AR101 after six months of dose escalation and a three-month therapeutic dosing phase. The ARTEMIS trial enrolled 175 peanut-allergic children and adolescents ages 4 to 17 from 18 sites in France, Germany, Ireland, Italy, Spain, Sweden and the United Kingdom.
A Biologics License Application (BLA) seeking approval for AR101 for the treatment of children and adolescents with peanut allergy currently is under review by the U.S. Food and Drug Administration (FDA), which is expected to take until late January 2020. The Allergenic Products Advisory Committee (APAC) of the FDA will review the BLA for AR101 at its meeting scheduled for September 13, 2019.
