Trump administration proposes plan to boost number of kidney transplants

The Trump administration unveiled several new rules Tuesday that aim to boost access to transplants for patients with kidney disease.

The Centers for Medicare & Medicaid Services issued a rule that overhauls oversight of organ procurement organizations (OPOs). The measures were last updated significantly in 2006, and the new proposed rule would change the recertification cycle for these organizations from every four years to annually.

CMS also wants to include new performance measures for these groups, such as donation and transplantation rates. The changes, if finalized, would take effect in 2022.

On a call with reporters Tuesday morning, CMS Administrator Seema Verma said the agency estimates the changes would lead to an additional 5,000 kidney transplants.

“Our proposed rule represents a fundamental shift in the way we assess OPOs,” Verma said.

The changes are borne out of an executive order signed by President Donald Trump in July that included a slew of initiatives to improve kidney care for patients and address the high costs associated with the disease.

Also as part of that order, CMS released five new payment models designed to drive greater use of home dialysis and increase access to transplants. Under one of the models, called End-Stage Renal Disease Treatment Choices, CMS said it will adjust participating providers’ payments up or down depending on their transplant and home dialysis rates.

Kidney care has been a focus for the administration for some time, as the Department of Health and Human Services launched a nephrology-centric accelerator, called KidneyX, in April 2018 and Secretary Alex Azar has spoken about how kidney care has “some of the worst incentives in healthcare.”

In addition to the rule from CMS, the administration also released a rule from the Health Resources and Services Administration (HRSA) that aims to ease some of the financial barriers to becoming a living kidney donor.

HRSA’s proposed rule would offer greater coverage for expenses associated with the donation, such as lost wages, childcare or eldercare. Kidneys transplanted from living donors typically produce better outcomes than those from deceased donors or compared to dialysis, according to HRSA.

HRSA Administrator Tom Engels said on the press call that the changes could lead to a notable increase in living kidney donations. About 96,000 people are on the waiting list for a kidney transplant, he said.

“Many potentially living donors may be willing and available to donate an organ to a family member, friend or an unknown recipient, but would be unable to afford the loss in income while out of work during the transplant process, which include pre-transplant evaluation, surgery, subsequent recovery time and follow up appointments,” Engels said.

“This proposed rule would remove this potential barrier to living organ donations,” he said.

https://www.fiercehealthcare.com/payer/trump-administration-proposes-plan-to-boost-number-kidney-transplants

AstraZeneca, Merck: FDA Panel Backs Lynparza in Pancreatic Cancer

AstraZeneca and Merck & Co. Inc. (MRK) said an U.S. Food and Drug Administration advisory panel voted to recommend lynparza for first-line maintenance therapy in pancreatic cancer.

The Oncologic Drugs Advisory Committee voted 7-5 to recommend lynparza as a first-line maintenance monotherapy for germline BRCA-mutated metastatic pancreatic cancer, the companies said.

The FDA in August accepted the supplemental New Drug Application for lynparza for this indication.

The ODAC provides the FDA with independent advice and recommendations on marketed and investigational medicines for use in the treatment of cancer. The FDA isn’t bound by the committee’s guidance but takes its advice into consideration.

In 2017, AstraZeneca and Merck unveiled an oncology collaboration to co-develop and co-commercialize lynparza.

https://www.marketscreener.com/ASTRAZENECA-4000930/news/AstraZeneca-Merck-Say-FDA-Panel-Recommends-Lynparza-in-Pancreatic-Cancer-29740411/

Data-sharing snafu due to cloud provider switch – DexCom

DexCom (DXCM +2.4%) says the recent failure of its G6 remote glucose monitoring feature was related to its change of cloud-computing service providers.

According to CEO Kevin Sayer, the company switched to a new vendor for its data-sharing feature, but then DexCom introduced new platform components that “weren’t configured for optimal performance.” Core processes within the platform were disrupted when these components failed.

The company is reviewing its computer systems and making changes to ensure that such a snafu does not recur.

https://seekingalpha.com/news/3526900-data-sharing-snafu-due-to-cloud-provider-switch-dexcom

How Novartis cancer drug Tasigna restores key dopamine lost to Parkinson’s

Researchers at Georgetown University have been trying to repurpose Novartis’ cancer drug Tasigna to treat Parkinson’s disease since 2013, when they showed it could clear toxic alpha-synuclein protein clumps in the brains of mice. But it wasn’t until 2017, when they moved Tasigna into a small phase 2 trial, that they started to understand exactly how Tasigna—a tyrosine kinase inhibitor—might work in the brain to relieve Parkinson’s symptoms.

The Georgetown researchers have gained new insights from that trial they believe offer critical clues to Tasigna’s action in the brain. They reported an increase in dopamine, the critical brain chemical that’s lost to Parkinson’s, among patients in the trial who were taking Tasigna (nilotinib). That increase, coupled with a decrease in neurotoxic proteins, may explain how Tasigna can stop the decline of both motor and non-motor functioning, they reported in the journal JAMA Neurology.

The trial included 75 Parkinson’s patients who either received 150 mg or 300 mg of Tasigna or a placebo. The trial was designed primarily to assess the safety of the drug in Parkinson’s, but the researchers also measured clinical outcomes, and they collected biomarkers from the patients’ cerebral spinal fluid.

They found that patients taking Tasigna had 20% less alpha-synuclein and 30% less tau, another toxic brain protein. They also had 50% more dopamine metabolites—a sign that clearing neurotoxic proteins may boost the ability of the brain to use dopamine.

After 15 months, motor ability improved among patients on the lower dose of Tasigna, while those taking placebo or the higher dose of the drug remained stable. All patients on Tasigna reported an improvement in quality of life.

The results suggested that Tasigna “stabilized the disease—a potential disease modifying effect that we haven’t observed with any other agents,” said lead investigator Fernando Pagan, M.D., Georgetown neurology professor and medical director of the GUMC Translational Neurotherapeutics Program, in a statement.

Tasigna was approved by the FDA to treat chronic myeloid leukemia at a dose of up to 400 mg per day. The drug does carry a black box warning, however, because by inhibiting Abl tyrosine kinase—a protein that’s critical for cellular functioning—it can cause sudden death. So part of the mission of the Georgetown team was to determine whether the drug could be safely administered to Parkinson’s patients at lower doses and still be effective.

At both 150 mg and 300 mg, the drug did not inhibit Abl tyrosine kinase, the researchers reported. Only two patients withdrew from the phase 2 trial due to adverse effects.

That finding suggests that Abl inhibition is unlikely cause the lowering of neurotoxic proteins that the Georgetown team observed. It’s possible that the blocking of other tyrosine kinases may be causing the beneficial impact in the brains of Parkinsons’ patients, they suggested.

Novartis supplied Tasigna for the study but is not otherwise providing financial support to Georgetown, which owns the intellectual property rights for use of the drug in some neurodegenerative diseases. The Michael J. Fox Foundation was among the early supporters of the Tasigna research. The phase 2 was supported by the Lasky-Barajas Family Fund and other donors, Georgetown said.

In March, the Georgetown team published data from the phase 2 trial showing that Tasigna may have other benefits in the brain. At a dose of 200 mg, the drug seemed to boost levels of TREM2, an anti-inflammatory protein in the brain.

The phase 2 trial is expected to be completed in 2020. Then the clinical findings will need to be confirmed in larger studies involving diverse populations of patients, Pagan said.

https://www.fiercebiotech.com/research/how-novartis-cancer-drug-tasigna-restores-critical-dopamine-s-lost-to-parkinson-s-disease

FDA raises doubts about benefits of Epizyme’s cancer drug ahead of AdComm

The FDA has picked holes in Epizyme’s filing for approval of tazemetostat, pointing to limited efficacy and safety concerns in its advisory committee briefing document. One analyst said the conclusions “read a bit harsh,” leading them to put the chances of a positive vote at no more than 25%.

Epizyme is seeking FDA approval of tazemetostat, an EZH2 inhibitor, in adults with metastatic or locally advanced epithelioid sarcoma who are not eligible for curative surgery. The filing is based on data from a non-randomized, open-label clinical trial that gave tazemetostat to around 100 epithelioid sarcoma patients.

In briefing experts on its advisory committee ahead of a meeting Wednesday, the FDA raised doubts about whether the objective response rate (ORR) seen in the EZH-202 trial is good enough.

“With limited clinical experience and lack of comparative data, FDA is concerned that the ORR of 13%  observed in Cohorts 5 and 6 of EZH-202 does not provide sufficient evidence of benefit to outweigh the risks of tazemetostat in patients with epithelioid sarcoma,” the agency wrote.

The FDA thinks the ORR of 13% may flatter Epizyme’s drug, noting that “the true response rate to tazemetostat may thus be as low as 4-7%” given the position of the 95% confidence interval. The agency compared that figure to the 24% ORR that won doxorubicin approval in soft tissue sarcoma in 1974, although that side by side comes with the caveat that response criteria have changed over the intervening years.

Drugs have received positive advisory committee recommendations on the basis of limited evidence of efficacy in the past, particularly in rare diseases such as epithelioid sarcoma, but tazemetostat is also hampered by a safety signal. While the FDA thinks tazemetostat is generally well tolerated and may have a better toxicity profile than standard therapies, it also pointed to “a clear risk of secondary malignancies” associated with use of the EZH2 inhibitor.

Michael Yee and his colleagues at Jefferies called the briefing document “pretty cautious” and “a bit harsh,” leading them to put the likelihood of a positive advisory committee recommendation at 20% to 25%. Yee’s peers at SVB Leerink struck a softer tone, calling the briefing document “relatively balanced,” but still came away from the FDA analyses thinking tazemetostat “does not appear to confer superior benefit to [existing] agents based on available data.”

If shared by the advisory committee and the FDA reviewers, that conclusion could sink Epizyme’s hopes of bringing tazemetostat to market in epithelioid sarcoma. That outcome would only be a small blow to Epizyme’s prospects, though.

Epithelioid sarcoma is a small indication—Yee puts the opportunity at less than $50 million—that is dwarfed by the size of the other market targeted by Epizyme. Yee and his colleagues think the case for tazemetostat in the second disease, follicular lymphoma, is much clearer, meaning Epizyme could file for approval in an indication worth an estimated $500 million even if the FDA rejects the drug in epithelioid sarcoma.

https://www.fiercebiotech.com/biotech/fda-raises-doubts-about-benefits-epizyme-s-cancer-drug-ahead-adcomm

PharmaMar files for FDA approval of small cell lung cancer drug

PharmaMar has filed (PDF) for FDA approval of lurbinectedin in relapsed small cell lung cancer. The filing tees PharmaMar up to become the first company to win approval for a new chemical entity in the disease in more than 20 years.

Lurbinectedin is designed to cause cell death by inhibiting activated transcription and inducing DNA double-strand breaks. Through this mechanism, PharmaMar thinks lurbinectedin can improve the prospects of small cell lung cancer patients who have progressed after receiving platinum-containing therapy.

PharmaMar ran a phase 2 clinical trial to generate data to back up that hypothesis. In the 105-subject small cell lung cancer cohort, PharmaMar linked lurbinectedin to a 35% response rate. Of the eight patients previously treated with immuno-oncology drugs, five responded.

The study also generated data on the duration of those responses. The median duration of response clocked in at 5.3 months, and the median overall survival was 10.8 months. One in 10 patients had ongoing responses 12 months into the trial.

PharmaMar achieved the best results in a subset of patients with chemotherapy-free intervals of more than 90 days, which it classed as having sensitive disease. In that subgroup, the response rate was 47%, as compared to 21% in patients with shorter chemotherapy-free intervals. The responses in the sensitive disease subgroup were longer, too.

The data are now with the FDA for review. PharmaMar thinks it has a shot at bringing lurbinectedin to market in the U.S. in the second half of next year. If PharmaMar achieves that goal, lurbinectedin will become the first new chemical entity approved in the indication since Hycamtin in the 1990s.

That fact paints a slightly misleading picture of the extent of innovation in the indication. In recent years, Bristol-Myers Squibb and Merck have won approval for Opdivo and Keytruda, respectively, in the indication, giving patients the option of receiving checkpoint inhibitors.

Opdivo and Keytruda came to market in the indication on the strength of response rates that fell short of the 35% achieved by lurbinectedin, although the unreliability of cross-trial comparisons makes the significance of that difference unclear. PharmaMar also has early evidence that lurbinectedin works in patients previously treated with immuno-oncology agents.

https://www.fiercebiotech.com/biotech/pharmamar-files-for-fda-approval-small-cell-lung-cancer-drug

Most cancer docs rely on pharma salespeople for info: survey

Here’s a stat drugmakers would love to tout: With the cancer drug market exploding, oncologists rely on pharma’s own sales reps for information about the latest drugs and study data—and, crucially, assistance in helping their patients afford their meds.

By a wide margin, in fact. Seventy-one percent of U.S. oncologists surveyed by Cardinal Health Specialty Solutions agreed sales reps play an important role in their new-product education.

While turning to the makers of the drugs for information makes logical sense, it’s still good news for drugmakers in general and pharma reps in particular. The sales rep role has been eroding as pharma companies turn to technology for doctor communications, for one thing, but more importantly, marketing scandals have tightened up rep access to many doctors.

Oncologists are more welcoming. Among the cancer doctors surveyed, 48% allow full access to sales reps, while 45% allow access with limits.

“Oncologists appreciate the pharmaceutical companies and they rely on them, particularly when it addresses a high unmet medical need,” said Joe DePinto, president of Cardinal Health Specialty Solutions, which conducts the oncology survey, now in its sixth year, in advance of Cardinal’s oncology summits.

The key value-adds ascribed to sales reps? Patient access and assistance programs (64%), followed by providing staff education (42%) and providing patient education materials (24%), were the key benefits listed by the 170 community and hospital cancer doctors surveyed over three months this fall.

However, sales reps are still just one of many resources oncologists use for information—key opinion leaders and online clinical support platforms ranked ahead of sales reps as more often-used channels. Overall, use of digital information and education continues to grow, DePinto said, with 73% agreeing that websites, internet and e-newsletters play an important role in finding new products.

“Pharmaceutical companies are a go-to, but physicians have access to more and more information, just like consumers, and there are multiple vehicles and they are clearly using all of them,” DePinto said.

Pharma companies should note areas of opportunity such as what oncologists name as the value they get and want from pharma. Their answers focus on what patients need to access specialty products and what physicians’ staff members need to navigate treatment approaches.

The survey also asked about the kind of content oncologists want from pharma companies, beyond clinical and safety trial data. The top answer named by 24% was patient outcome studies based on real-world evidence, followed by comparative effectiveness studies (20%).

“There continues to be growing interest in real world evidence,” DePinto said, “Two-thirds of the respondents said real world evidence is necessary to inform treatment decisions—that’s substantial.”

https://www.fiercepharma.com/marketing/survey-oncologists-finds-large-majority-rely-pharma-sales-reps-for-new-drug-education