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

STAT

Biotech

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

By Rebecca Robbins @rebeccadrobbins

https://www.statnews.com/2018/02/22/james-xue-biotech-ceo-china-fda/

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?

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“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.”

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

BioWorld

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

Actionable Intelligence • Incisive Analysis

February 7, 2018 Volume 29, No. 26

http://www.bioworld.com/content/chinas-canbridge-nabs-pumas-nerlynx-her2-breast-cancer-70m-deal-0

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
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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.

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Canbridge nabs rights to Aveo’s ErbB3 antibody for esophageal cancer

By Shannon Ellis
Staff Writer

Tuesday, March 22, 2016

SHANGHAI – Canbridge Life Sciences Ltd., a privately held biopharma in Beijing, has in-licensed AV-203 , a clinical-stage ErbB3 (HER3) inhibitory antibody candidate from Aveo Oncology Inc., of Cambridge, Mass. While the candidate has been tested in numerous tumor models, Canbridge will develop AV-203 in esophageal squamous cell cancer (ESCC), the most prevalent form of esophageal cancer especially in China where half of all new cases arise.

A virtual biopharma with a team of 20, Canbridge has a China-focused strategy by seeking out global candidates that can meet a specific unmet need in China or Asia. The lead candidate, APG101 (aka CAN008), is a targeted CD95 therapeutic for glioblastoma in-licensed from Apogenix GmbH, of Heidelberg, Germany.

In this deal, Aveo will receive a $1 million up-front payment with the potential to receive $133 million downstream if all goes according to plan. Terms also call for Aveo to receive a tiered royalty with a percentage range in the low double digits on net sales.

In return, Canbridge has the right to develop AV-203 (aka CAN017) globally, excluding North America, for numerous indications although ESCC is the top priority.

“This is not a regional deal; it is worldwide outside of North America,” James Xue, Canbridge CEO, told BioWorld Today. “When you come to a valuation, you build in both geographies as well as indications. Because it is our decision to investigate esophageal carcinoma first, but it has potential in other types of tumors where squamous cell is dominant or has a significant presence, we feel to show our seriousness a modest up-front payment was appropriate.”

Canbridge will cover the costs for developing CAN017 for squamous cell esophagus cancer to demonstrate proof of concept including additional in-China manufacturing requirements, preclinical and clinical studies all the way to phase IIa.

The two sides leave open the option of working more closely to co-develop the candidate once Canbridge completes proof of concept in China.

“This agreement allows us to further advance AV-203 development by leveraging the resources of a motivated partner in Canbridge,” said Michael Bailey, Aveo’s president and CEO. “Importantly, it also allows us to retain North American rights for future development for a third clinical stage drug candidate, providing Aveo with a robust portfolio of oncology therapeutics.”

THE GENZYME CONNECTION

Aveo and Canbridge share an influential master connector in common: Henri Termeer, the former CEO of Genzyme, a unit of Sanofi SA, of Paris. Termeer is the chairman of Aveo and also Canbridge’s chief advisor. (Before branching out on his own, Xue was the China general manager for Genzyme.) Having Termeer on the team has been a boon for Canbridge in making ties with the U.S. and Europe.

“We talked about how Canbridge has an interest in Asian disease and whether in their pipeline there was something where we could leverage our strengths, and it came to the AV203,” said Xue. “Aveo had already completed a phase I study in the U.S. but because of their priorities, they probably will not have any immediate plans for post-phase I development. We took a closer look and saw the relationship with squamous cell type carcinoma. We moved pretty quickly after determining that since Asia has over half the world prevalence of esophageal cancer.”

For its part, Aveo has had a bumpy ride after its lead candidate, tivozanib for renal cell carcinoma, ran into costly regulatory complications with the FDA during phase III trials. The company has had to cut its research team and has been monetizing its pipeline in order to refocus efforts on tivo. (See BioWorld Today, Feb. 18, 2014.)

TOO MANY PICKLED VEGETABLES

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A China-focused statistical review published in Thoracic Cancer estimated there were 287,632 new cases of ESCC diagnosed and 208,473 deaths in 2010. Esophageal cancer incidence ranked fifth of all cancer types in China, with a rate of 21.88 per 100 000. For both incidence and mortality, men living in rural areas were most likely to be affected, peaking at the age 80 to 84.

In certain rural areas in Henan, Hebei and Shanxi, the incidence rate shoots to the highest in the world, greater than 100 cases per 100,000 according to a study in the Journal of Epidemiology. Other high incidence areas are found in the provinces of Sichuan, Anhui, Jiangsu, Hubei, Fujian, Guangdong and Xinjiang.

Studies show there is a complex interaction between genetic factors when combined with alcohol consumption, smoking and poor nutrition that can cause ESCC. It is believed diets containing a high quantity of pickled vegetables (with nitrosamine content) are also to blame.

 

ERBB3 (HER3)

ErbB3 belongs to a family of four proteins that also includes EGFR (HER1) and HER2 tyrosine kinase receptors. ErbB3 stimulates cancer growth and its overexpression generally correlates with poor prognosis.

AV-203 selectively targets the receptor ErbB3 and demonstrated preclinical activity in a number of different tumor models including breast, head and neck, lung, ovarian and pancreatic cancers. The preclinical data further showed the potential for heregulin, the only known ligand for ErbB3, to serve as a biomarker predictive of AV-203 anti-tumor activity.

Aveo completed a phase I study showing no dose-limiting toxicities at a maximum dose of 20 mg/kg.

Plans are already under way at Canbridge to make use of PDX mice models to continue testing CAN017 in tumors from Chinese squamous cell esophageal cancer patients. Company execs expect to be ready to submit an investigational new drug application next year, and take advantage of China’s new guidelines for innovative drugs.

“We are going to start a human trial in China first and hope to take advantage of the green channel approach. Because it is [CAN017 targets] a major malignant tumor, has a Chinese specificity, and we are going to manufacture the product in China, it will allow us to tap into the national guidance,” said Xue.

CHINA AS A LAUNCHPAD TO THE WEST

Meeting China’s significant unmet medical needs is the stated aim of many of China’s most promising biopharmas, in large part because there is such a gap between the drugs available in developed markets and in China – with only about 30 percent drugs available in China.

“The big multinational companies have set their center of gravity and development capabilities mostly in the West,” explains Xue. “Many products are successfully launched with Western populations as a priority. If they happen to be able to address a disease in the Asian population then it is perfect. However, if prevalence in Asia is much greater than in the West and you are still using this algorithm to the do the global launch then it will be quite a missed opportunity for those companies. That is where companies like Canbridge can come in.”

But with Canbridge’s first foray into a global rights deal, the company is joining a small band of companies that are hoping to pull the center of gravity slowly their way.

“Once the data generated in China begins to look very promising, we have strong confidence that we can replicate the data in the West,” said Xue. “We can utilize Asia as a base to develop innovative therapies for the global patient, instead of the other way around.”