It’s breathtaking’: A Chinese biotech CEO weighs in on policy changes remaking China’s FDA



It’s breathtaking’: A Chinese biotech CEO weighs in on policy changes remaking China’s FDA

By Rebecca Robbins @rebeccadrobbins

February 22, 2018

With China’s biotech sector on the rise, changes are afoot at the agency tasked with regulating the country’s pipeline of new drugs.

In recent months, China’s version of the U.S. Food and Drug Administration, known as CFDA, has introduced a host of new regulations meant to make drug makers happy: Companies can now submit certain datafrom clinical trial sites outside of China. More Chinese hospitals can run trials. Manufacturing need no longer be done in-house. And drug makers weary of waiting for a green light to proceed with a safety study could soon be allowed to go ahead if they don’t hear back from the agency within 60 days.

James Xue, CEO of Beijing-based CANbridge Life Sciences, has had a front-row view of it all. He’s been interacting with CFDA officials on and off for the past 15 years, first in running Genzyme’s China operations and now in steering his own biotech company seeking approval for four oncology drugs. And Xue knows how drug approval works in the U.S., too: Born and raised in China, Xue did his graduate education and started his biopharma career in the U.S. before coming home as part of Thousand Talents, a Chinese government recruitment program that’s seen both successes and struggles.

So what does the raft of changes at the CFDA look like to such a tuned-in observer? We called up Xue to get his impressions.

What do you make of all these changes at the CFDA?

“In the last 12 months, I have experienced more reform and drastic change for better [than] over the 14 years before that combined,” Xue said. “It’s breathtaking, in a very good, very positive way.”

James Xue, CEO of CANbridge Life Sciences CANbridge Life Sciences

The palpable change, he says, extends to how quickly CFDA officials respond in correspondence about his company’s applications — a change he attributes to the agency’s moves to cut the backlog of applications for old generic products.

What’s the biggest difference between working with China’s FDA and the U.S. FDA?

“The biggest difference prior to the reforms last year was the mentality,” Xue said. The CFDA was “not really risk taking at all.”

But the recent changes at the CFDA are making it not so different to work with drug regulators in China compared to those in the U.S., Xue said.

How have changes at the CFDA shaped your strategy at CANbridge?

Of the four drugs CANbridge is trying to get approved in China, two have already been approved in other countries. For the other two molecules, Xue is going to China for first-time approval.

Now that his team can submit data from clinical trial sites outside of China, Xue is taking a second look at the data from global clinical trials supporting several of the molecules his company has licensed to try to commericalize in China. “Before, we had to reproduce those data,” he said.

That same change has Xue thinking more about future hiring plans in North America. And another recent policy change allowed him to open a clinical trial site in Taiwan in pursuit of an approval in China.

Have any of the recent changes at the CFDA made it harder for you to do business or move your products along swiftly?

Xue pointed to a new CFDA policy that allows drug makers to contract out their manufacturing to a plant in China, instead of having to set up a plant in-house. That’s a “very positive” change, Xue said, but it doesn’t go far enough. He’d like to see it extend to manufacturing plants outside of China.

“I wish the CFDA would be more bold in allowing ex-China manufactured product to be entitled to the same benefits of the reform,” Xue said. That way, “we would not need to duplicate efforts by transporting a manufacturing process that is already very matured and established in the West for the sake of bypassing this laborious process.”

What challenges remain in working with the CFDA?

“I think the biggest pain point is still the truly innovative drug categories,” Xue said. When it comes to cutting-edge science, “the Chinese FDA is still not yet experienced enough to review the protocol or to give constructive input in making the protocol less risky” and more likely to get approved.

When you talk with U.S. biotech CEOs, how aware are they of all these changes at China’s FDA?

“I’m surprised, actually,” Xue said. “Their senior executives are very tuned in to the recent reforms in China. I have no doubt that they affect how they do their corporate strategy on a global basis. Nobody can afford to deprioritize China’s rise.”

China’s Canbridge nabs Puma’s Nerlynx for HER2+ breast cancer in $70M deal


The news source of record covering the development of innovative human therapies

Actionable Intelligence • Incisive Analysis

February 7, 2018 Volume 29, No. 26

or click here for a PDF version BioWorld 2

China’s Canbridge nabs Puma’s Nerlynx for HER2+ breast cancer in $70M deal

By Shannon Ellis, Staff Writer

SHANGHAI – Beijing’s Canbridge Life Sciences Inc. has acquired the greater China rights to Puma Biotechnology Inc.’s Nerlynx (neratinib) as an adjuvant for early stage HER2-positive breast cancer and other HER2 tumors, such as gastric cancer, which is highly prevalent in China.

The deal will provide Puma with an up-front payment of $30 million, with the possibility of another $40 million upon regulatory milestones. Royalties and sales milestones could also provide Puma with further payments.

Nerlynx, an irreversible tyrosine kinase inhibitor, was approved by the U.S. FDA in July. But the Los Angeles-based company encountered pushback from Europe’s regulators, with the Committee for Medicinal Products for Human Use (CHMP) indicating a negative trend vote last month. (See BioWorld, July 19, 2017, and Jan. 25, 2018.)

With poor prospects in Europe, Canbridge remains steadfast about Nerlynx’s chances in greater China. “We assessed the opportunity and even with the recent news from Europe, we will not waver in terms of our position to get this product to patients in China,” James Xue, Canbridge chairman, CEO and president, told BioWorld. “I want to emphasize this is a brand new drug that received U.S. FDA approval in an area that has very little treatment options and has a strong case for us to present to the authorities in our geographies, including mainland China, Taiwan, Hong Kong and Macau.”

Nerlynx is approved in the U.S. as an adjuvant for patients using Herceptin (trastuzumab, Roche Holding AG)-based therapy with HER2-positive breast cancer. About 20 percent to 25 percent of breast cancer patients overexpress the HER2 protein.

After a course of Herceptin, patients often have no additional treatment options, explained Xue. Depending on the individual, within about five years a significant number of patients – up to 25 percent – will find the cancer recurs in a very vicious form. Many patients lacking treatment options will die within six months; Xue called it “a very dire situation.” In China, that is especially so. “In terms of Chinese patients, the Chinese breast cancers are more aggressive compared to the western form and occur in a younger age group relative to the western patient population,” said Xue.

Assessing the global phase III MRCT data from Puma, Xue said a significant number of patients taking Nerlynx had reduced rates of recurring cancer vs. the comparator (according to Puma’s release it can be 34 percent). “This is a major accomplishment and clinical benefit for patients who do not have recurring cancer; they will live over five years,” Xue said. “And for those with recurring cancer, it allows those patients to have a chance at extended disease-free survival.”

Accelerated approval in China possible

The large amount of data that Puma collected in its global pivotal study may help Canbridge seek accelerated approval in China. Post-ICH (International Council for Harmonisation) admittance, China’s regulators have said they will accept global data. Since a portion of the data collected by Puma also included Chinese patients and those of Asian ethnicity, there is a chance that Canbridge may be able to seek approval without a clinical study in China, or only a limited one.

“We believe that we will be able to leverage the existing data to a maximum extent for a shortened market approval pathway,” said Xue. “We will leverage the data that Puma has already built on a global scale, including Asian patients with their pivotal study. Over 2,000 patients enrolled in the pivotal study over five years – it is one of the most sophisticated studies ever done in breast cancer.”

But in Europe, regulators have raised concerns over the clinical relevance and risk-worthiness of Nerlynx in extended adjuvant use for women with early stage, HER2-positive breast cancer and asked for Puma to take “additional steps.”

Puma said the CHMP found a benefit-risk assessment for Nerlynx to be negative since it was based solely on evidence from a single pivotal trial and because “two- and five-year invasive disease-free survival benefits observed to date may lack sufficient clinical relevance.”

Another factor Canbridge will need to work through when discussing Nerlynx with Asian regulators are the side effects of Nerlynx, including grade III diarrhea. “Puma did a good job to educate us about how they developed effective patient management protocol for the side effects,” Xue said. “We looked at the data for the prevalence and seriousness of the diarrhea … the protocol developed by Puma should be very straightforward for us to adopt in China.”

Meanwhile, in the U.S., Puma is seeking to widen the scope of use for Nerlynx to more HER2-expressed cancers in a basket trial for patients with breast, cervical, biliary, salivary and non-small-cell lung cancers.

Canbridge will take the lead on gastric cancer, which is highly prevalent in China. The company will also seek out approval for other forms of HER2-positive cancers as well, including late-stage metastatic breast cancer in China.

Getting market ready

With many of China’s regulatory hurdles now lowered, Canbridge, like many Chinese biotech startups, is getting market ready for the first time. The firm’s plan is to see Nerlynx on the market by mid-2019. In advance of that, Canbridge’s CAN-002 for mucositis caused by radiation or high-dose chemotherapy should receive CFDA approval.

“The timing of this deal is excellent in terms of building a full-fledged commercial presence which is already underway,” said Xue. “This is transformative because it accelerates our vision to build a virtually integrated company from development to full commercialization. My team and I are very excited about Puma’s decision to choose us as a partner. We want to be

 “I want to emphasize this is a brand new drug that received U.S. FDA approval in an area that has very little treatment options and has a strong case for us to present to the au­thorities in our geographies, including main­land China, Taiwan, Hong Kong and Macau.

James Xue

Chairman, President/CEO, Canbridge

known as the partner of choice in China and greater Asia area for such opportunities.”

The remainder of Canbridge’s pipeline is more early stage. CAN- 008 for glioblastoma multiforme is already in phase I trials in Taiwan. The biotech holds the greater China rights for CAN-008, which has been designated a MAH (marketing authorization holder) pilot project in China where it is seeking an IND. In addition, Canbridge’s CAN-017 is also seeking an IND in China for squamous cell esophageal cancer. Canbridge holds global rights for CAN-017, excluding North America.

Lumendi plans sale following regulatory approval and product launch, CEO says

Endoscopic devicemaker Lumendi said it plans to pursue a sale following the pending launch of its DiLumen C2 device in April, said company CEO Peter Johann.

The London-based company has been in discussions about potential distribution partnerships and a potential sale of the company for the past six months, Johann said on the sidelines of the 2018 JP Morgan Healthcare Conference.

To read the full article click on the link Mergermarket1.18

Stigma Against Mental Illness Is Built Into Health Care System

Stigma Against Mental Illness Is Built Into Health Care System

Editor’s note: This is the second of a three-part series.

Thursday, January 4, 2018

By Kenny Goldberg

When Kerry Martin was in graduate school at Harvard, she was deeply troubled. She was suffering from bipolar disorder. She was struggling with her sexuality.

To make matters worse, her mother had recently attempted suicide.

One day, Martin worked up her courage and made an appointment at Harvard’s Mental Health clinic.

“And I went in, and I met with a woman who was just getting her degree, I guess,” Martin remembered. “And I just poured my heart out to her. I said, ‘here’s what’s going on with me, my family. I think I’m gay. I’m having a real hard time with this.’”

But people with serious mental health challenges are sometimes considered to be different, dangerous or even beyond help. That same kind of stigma against mental illness can exist in our health care system, too.

Part One: For Those With Mental Illness, Battling Stigma Is First Step In Getting Help

When Martin got back to her apartment later that day, the therapist called her on the phone.

“And she says to me, ‘Kerry, I can’t help you.’ And I just kind of like, what? And she’s like, ‘I can’t help you’. And I was gonna have to ring somebody else. I’m like, I thought to myself, I’m beyond help.”

Martin felt hopeless. A few months later, she tried to kill herself.

Her roommate found her and called an ambulance.

Kerry Martin, founder of Hope Xchange, is shown on July 12, 2017.

Martin remembers being in the emergency room, writhing around on a gurney, while a nurse was trying to stick a tube down her throat.

“The nurse said to me, ‘Lay still, you did this to yourself.’ And I will never, ever forget that comment,” Martin said. “It’s like, you want compassion. Yes, I did this to myself, I guess I did. But at that moment, that’s the last thing I wanted to hear.”

Today, Martin runs the nonprofit Hope Xchange. It’s a phone and text-based service that focuses on preventing suicide in the LGBTQ community and in people with bipolar disorder.

Martin tries to provide the kind of support and compassion she wished she would have gotten years ago.

Belittled and dismissed

It’s not unusual for people with a mental illness to say they’ve felt belittled and dismissed by health care providers.

Some believe there’s a certain degree of stigma against mental illness built into the health care system.

Dr. Michael Plopper is medical director at Sharp Mesa Vista Hospital in Kearny Mesa, the largest private mental health facility in Southern California.

He said Medicare, for example, has a lifetime cap on the number of days a person can stay in a psychiatric hospital.

“Whereas, that’s not true for physical health. So still, to this day, Medicare discriminates in that way,” Plopper said.

Then there’s a federal policy called the IMD exclusion.

It prohibits fee-for-service Medicaid programs from covering inpatient care in free-standing mental health facilities like Sharp Mesa Vista.

“So what that does is, creates a logjam for these people, it creates problems in access to care for people with Medicaid,” Plopper said. “And so that’s a federal discriminatory law.”

Photo credit: Katie Schoolov

Judi Holder, an administrator with RI International, is shown Aug. 23, 2017.

Low expectations

Judi Holder is an administrator with RI International, an agency that provides peer-support services for people with mental health challenges.

Years ago, Holder was in psychiatric care herself. When she was diagnosed with borderline personality disorder, she was faced with a life of lowered expectations.

“I was basically told that it was important that I accept the fact that I was ill, accept the fact that that was who I was now, and told that I could never work again,” Holder recalled.

Holder remembers feeling worthless.

“Being told to kind of accept this new life, where there were no responsibilities, no expectations, was almost worse than the mental health challenges I was experiencing,” Holder said.

Her breakthrough came when she took a peer support class. The teacher had suffered from severe mental illness but was high functioning and fully employed.

“There was certainly a lot of doubt on my part,” Holder remembered. “But there was just that tiny glimmer of hope that said, maybe that can happen for me, too.”

Holder said there are plenty of caring and competent mental health providers. But she believes if all they see are severely troubled people, they just don’t expect people to get well.

“And so, in order to look past that, you have to be open to the perspective that what you see is not all there is,” she said

For Those With Mental Illness, Battling Stigma Is First Step In Getting Help

For Those With Mental Illness, Battling Stigma Is First Step In Getting Help

Nearly one out of five Americans suffer from it. But that hasn’t prevented the stigma of mental illness from being a powerful and damaging force.

Editor’s note: This is the first of a three-part series.

Wednesday, January 3, 2018

By Kenny Goldberg

Evan Hilliard had a tough childhood.

His father died when Hilliard was seven. He remembers having his first thoughts of suicide shortly after that.

At age 13, Hilliard spent a month-and-a-half in a psychiatric hospital.

When Hilliard got out, he didn’t tell his classmates where he had been.

“And that was because of stigma, ’cause I didn’t want to be labeled,” Hilliard recalled. “It’s already hard to fit into school, so I didn’t want any other hardships with that.”

Nearly one out of five Americans suffer from mental illness. But that hasn’t prevented the stigma of mental illness from being a powerful and damaging force.

Hilliard was initially diagnosed with depression. Then bipolar disorder. Then schizoaffective disorder. But he never talked about it.

Hilliard was hospitalized in 2011 for the fifth time. When he was released, he decided not to keep his condition secret anymore.

Evan Hilliard, who’s suffered from mental illness for much of his life, is shown on Aug. 1, 2017.

“I just didn’t want to die without anybody knowing who I was,” Hilliard said. “And I felt like I was on the road to killing myself. I was thinking about killing myself just about every single day since I was nine.”

Stigma is destructive

The stigma of mental illness is a destructive force. It prevents people from admitting they have a problem. That stigma also prevents people from seeking help. And it can increase the pain experienced by those who are struggling to get well.

Michelle Ahkoi, who has bipolar disorder, believes the mental illness stigma is everywhere, especially in the media.

“The media portrays us as like crazy people, or we’re gonna hurt you,” she said. “And sometimes, yes, we go through hospitalizations, or things that are a little intense, like my manic episodes, but I don’t hurt people.”

Mental illness equals violence?

Yet many Americans equate mental illness with violence.

For example, after the November mass shooting at a Texas church, President Trump said guns weren’t the problem.

“I think mental health was the problem here,” Trump said at a press conference. “This was, based on preliminary reports, a very deranged individual.”

Dr. Michael Plopper, medical director at Sharp Mesa Vista Hospital, is shown, June 23, 2015.

Dr. Michael Plopper, medical director at Sharp Mesa Vista Hospital, the largest private mental health facility in Southern California, said Trump’s language was way off base.

““I think that that is very stigmatizing,” he said, referring to the president’s remarks. “So, we’re having to overcome that type of rhetoric.”

Plopper believes when it comes to violence and mental illness, people need to get a reality check.

“So there’s this misbelief that people with mental illness are more prone to be violent. There’s a very small percentage of people with very specific type of disorders in which that can be true,” he said. “But the vast majority of people with all types of mental illness, from minor to severe, are not violent people.”

Dr. Jim Dunford, professor emeritus of emergency medicine at UC San Diego School of Medicine, said despite the advances in awareness and treatment, there’s a persistent notion that mental illness is a moral failing.

“There is a continuing belief on the part of some people that you’re weak, right? The old theory was that you had to cope with these things on your own,” Dunford said.

As Evan Hilliard explained it, for most of his life, that kind of stigma made him feel terrible.

“I felt like I couldn’t be myself, I felt like I couldn’t be vulnerable with other people, I felt like I couldn’t be authentic,” he said.


Today, Hilliard works as a peer support specialist at a local nonprofit agency.

He’s also on the board of the nonprofit Impact Young Adults. The group’s mission is to encourage young people with mental health challenges to reach out, make friends, and socialize.

Impact Young Adults believes mental illnesses are chronic conditions like diabetes or hypertension. And just like those disorders, mental illnesses need to be properly treated and managed.

In other words, mental illnesses are medical conditions – they’re not a sign of weakness.

Now that he’s accepted his condition, Hilliard has stopped concealing it, and he’s trying to take an active role in fighting stigma.

“I think it’s important to show people what mental illness really looks like, so that we don’t label people without understanding what’s going on,” Hilliard explained. “And I just want to help. I know for a long time I was suffering. And I know many other people are suffering, too.”

DiLumen Endolumenal Interventional Platform (EIP)


Surgeons interested in expanding their alternatives in pursuing minimally invasive options need to be attuned to new tools coming into the marketplace. One of the most intriguing devices is the DiLumen Endolumenal Interventional Platform (EIP), manufactured by Lumendi.

Click on the link to read the full article Surgical Products 12.11.17

Plaxgen Working to Expand Sales of Statin Test, Explore Lipid Morphology Data


Plaxgen Working to Expand Sales of Statin Test, Explore Lipid Morphology Data

Nov 21, 2017 | Adam Bonislawski

NEW YORK (360Dx) – Diagnostics firm Plaxgen is looking to expand sales of its StatRes test for predicting patient response to statins.

The Fremont, California-based company has been offering the test on an early-access basis through an agreement it signed last year with St. Joseph Health, a regional hospital system with five hospitals throughout Northern California and is now working to expand its reach through similar agreements with additional hospitals, said Shanmugavel Madasamy, Plaxgen’s founder and CEO.

The company is also investigating whether data on the morphology of cholesterol particles could help identify patients at risk of cardiac events and guide statin therapy. In September, company researchers and their collaborators published a study in the Journal of Visualized Experiments in which they found links between particle morphology and abnormal lipid levels, and observed changes in patient particle morphology following treatment with various statins.

Launched by Madasamy in 2007, Plaxgen uses a system that combines the capture of target biomarkers on plaque arrays with the isolation and analysis of those markers by techniques including flow cytometry and MALDI mass spectrometry.

The company’s plaque array system works essentially as an enrichment step, allowing researchers to investigate only plaque-related serum proteins, as opposed to the full serum proteome. The arrays are composed of soluble plaque-forming constituents that are then incubated with serum from test subjects. These plaque-forming constituents work as substrates for the plaque-related serum analytes, allowing for their pull-down and subsequent analysis.

Last year, the company published a paper on the StatRes test in the American Journal of Cardiology looking at 30 serum samples from patients with high cholesterol who went on to receive treatment with statins. It found that it was able to predict response in 13 of 15 patients receiving simvastatin and 12 of 15 patients on atorvastatin.

The company is now putting together a larger clinical validation trial in which it plans to follow thousands of patients over the course of four years. Madasamy said it hopes with that data to take the test through the US Food and Drug Administration regulatory process. Plaxgen currently offers the StatRes test as a laboratory-developed test through its CLIA lab.

In the JoVE study, the company paired its plaque capture system with analysis by imaging flow cytometry, which allowed it to study the shape of circulating cholesterol particles.

“In general, it’s understood that in atherosclerosis, not only the number of particles, but also the morphology and size of the particles, plays an important role [in the condition],” Madasamy said. However, he noted, the role of morphology has seen relatively little study compared to work focused on quantification of lipids involved in atherosclerosis.

The researchers used Plaxgen’s technology coupled to imaging flow cytometry to compare the morphology of cholesterol particles in 50 patients with plaque disease and age-matched healthy controls, and found that the subjects with plaque disease had higher levels of linear-shaped particles (mean of 18.3 percent) compared to healthy controls (mean of 11.1 percent).

They also used the platform to look at the changes in morphology of cholesterol particles in response to treatment with various lipid-lowering agents, incubating isolated particles with lovastatin, simvastatin, atorvastatin, rosuvastatin, fluvastatin, ezetimibe, fibrate, niacin, and omega-3 fatty acid. They analyzed drug-induced morphology changes and found that lovastatin, simvastatin, atorvastatin, and ezetimibe induced the formation of both linear and globular morphologies, while rosuvastatin, fluvastatin, fibrate, niacin, and omega-3 fatty acid induced formation of only globular particles.

The results, Madasamy said, suggest both the role of morphology in plaque disease and that different lipid-lowering drugs may have different effects on this morphology.

“We believe that in specific populations, the morphology data could be a biomarker to complement [existing] diagnostics to improve accuracy,” he said. “Because, yes, a patient’s lipid levels can look fine, but they can still have a heart attack or stroke.”

Madasamy said Plaxgen is now applying its morphology analysis to the amyloid-beta plaques characteristic of Alzheimer’s disease, another area of focus for the company.

“We are expanding to that and have data that we hope to publish next year,” he said.