2017 A Takeoff Year For China Drug Approvals?

2017 may become a banner year for the China FDA as the agency officially joined the ICH process and began aligning more closely with the US FDA, approving over 25 innovative new drugs so far with an increasing focus on treatments for cancer, hepatitis and orphan diseases.

When people look back at the history of new drug approvals in China, the year of 2017 is likely to stand out as the time the country decided decisively to tackle the drug lag issue. It has generally taken three to five years for a new drug to get approved in China after it has gained a greenlight in the US or Europe.

Now, however, this situation has started changing.

Throughout 2017, China's top regulatory agency, the China FDA, issued a plethora of new policies, ranging from allowing more foreign data to support new drug approvals, to new rules on patent linkage and data exclusivity. The moves were billed by some analysts as "historic and unprecedented". (Also see "China FDA Proposes Sweeping Reforms To Incentivize Innovation" - Pink Sheet, 15 May, 2017.)

There were 26 new drug approvals (NDAs) last year by the CFDA, according to data compiled by The Pink Sheet. In comparison, the agency approved 23 NDAs for chemical drugs and nine biologic product approvals (BLAs) in 2016.

As the year came to an end, what were some of the significant new drugs that successfully sailed through the CFDA and what messages did these approvals convey? The Pink Sheet takes a deep dive into the data and examines the underlying trends.

Harvest Time: Antiviral Treatments

Among the NDAs, chronic disease treatments continued to dominate. Out of the total, roughly 25% - or six out of 26 – were innovative therapies approved for hepatitis C, a prevalent viral infectious disease in China.

The specific products included Sovaldi (sofosbuvir) from Gilead Sciences Inc., Olysio (simeprevir) from Johnson & Johnson, Daklinza (daclatasvir) from Bristol-Myers Squibb Co., Exviera (dasabuvir) from AbbVie Inc., Sunvepra (asunaprevir) from BMS, and AbbVie's three-drug combination Viekirax (ombitasvir, paritaprevir and ritonavir).

The flurry of new HCV drug approvals also set the stage for competition between Gilead, J&J, AbbVie, and BMS's all-oral, direct-acting antiviral products in China.

HCV aside, other anti-infectious treatments also bagged approval, including the combination HIV therapy Triumeg (abacavir, dolutegravir, and lamivudine), which was developed by ViiV Healthcareand is marketed in China by GlaxoSmithKline PLC.

Being a populous country, China continues to emphasize new drugs for unmet clinical needs for major infectious diseases, such as chronic hepatitis and HIV, and there are expected to be more approvals for antivirals in the years to come.

Crowding The Gate: Oncology Drugs

Another critical condition, cancer, saw five NDAs, and one abbreviated NDA. Imbrutinib from Pharmacyclics Inc., now part of AbbVie, Tagrisso from AstraZeneca PLC, Jakavi from Novartis AG, and generic pemetrxed from domestic firm Sichuan Huiyu, highlighted China's desire to expedite getting new anticancer therapies to the market.

Efficacy and clinical need are ranked as key criteria for gaining approvals in China. Roche's Zelboraf (vemurafenib), for one, was approved and launched for melanoma in 2011 in the US and other countries, but Chinese patients with the often fatal skin cancer had no new treatments.

Despite metastatic melanoma having a much lower incidence in China - 0.48 out of 100,000 people compared to 21.6 in the US - the CFDA said in its approval report that the clearance reflected proven efficacy, a tolerable safety profile, and that the current standard care lacked efficacy to improve overall survival and had high toxicity.

The approval of Tagrisso reflected a lack of treatment options for lung cancer patients who have the T790M mutation and resistance to current EGFR-TKI agents, noted the CFDA. The drug has shown significant efficacy in improving progression-free survival and the approval will meet the urgent clinical need for NSCLC patients with the mutation, noted the agency in the approval report.

Approval Acceleration

Cardiovascular treatment Entresto (sacubitril and valsartan) from Novartis AG received the CFDA nod two years after its US approval, indicating that the CFDA may be closing the drug approval lag.

The agency has previously promised to eliminate a backlog of approval filings and to start new drug reviews on a rolling basis, from 2018.

Throughout 2017, the agency issued a series of guidances, ranging from allowing the use of foreign data towards new drug approvals to streamlining the qualification process for clinical sites, from a previous certification procedure to a simplified filling process.

Against this backdrop, several drugs pending approval have sailed through the process, including Sumitomo Dainippon Pharma Co. Ltd.'s Lonasen (blonaserin) for schizophrenia and Pfizer Inc.'s Xeijanz (tofacitinib) for rheumatoid arthritis.

Orphan diseases is another focus for accelerated approvals in China, with Sanofi's Myozyme (aglucosidase alfa) cleared for Pompe's disease and Boehringer Ingelheim GMBH's Ofev (nintadenib) for idiopathic pulmonary fibrosis (IPF).

The CFDA recently released a list of 17 novel drugs that are being selected for accelerated review for clinical trial approvals (CTAs), among them five orphan products. They include Roche's R04074067 for Duchenne muscular dystrophy, a neuromuscular disorder in children. Others include a Factor VIII preparation for hemophilia from Chengdu RongSheng Pharma, Zavesca (miglustat) for Niemann-Pick disease type C from Actelion Pharmaceuticals Ltd., and an expanded indication for ibrutinib.

"There are three things in the new Chinese regulations which are particularly helpful for all drug makers. First is the wide conditional approval based on the clinical efficacy trend; second is the patent linkage which can potentially give patent extensions for innovative drugs; and thirdly is that now innovative drugs can outsource manufacturing" said BeyondSpring Inc. CEO Huang Lan in an interview last year. (Also see "BeyondSpring CEO: China's New System Will Get Our Drug To Market Faster" - Scrip, 5 Dec, 2017.) .

BeyondSpring is developing a novel treatment for non-small cell lung cancer for the market

Highlights Of CFDA NDAs In 2017

No	Product	Active ingredient		Dosage	Indication	MAH holder	Approval
1	Ofev	nintedanib		100mg tablets	IPF	Boehringer Ingelheim	Sept. 20, 2017
2	Olysio	simeprevir		150mg capsules	hepatitis C	J&J	Aug. 24, 2017
3	Daklinza	daclatasvir		60mg tablets	hepatitis C	BMS	June 2, 2017
4	Exviera	dasabuvir		250mg tablets	hepatitis C	AbbVie	Sept. 20, 2017
5	Imbruvica	ibrutinib		140mg capsules	B-cell lymphoma	Pharmacyclics	Aug. 24, 2017/
6	Zyvox	linezolid		5ml:100mg oral suspension	antibacterial	Pharmacia &Upjohn	Feb, 21, 2017
7	Entresto	sacubitril and valsartan		50mg,100mg, 200mg tablets	heart failure	Novartis	Sept. 20, 2017
8	Sunvepra	asunaprevir		100mg capsules	hepatitis C	BMS	April 24, 2017
9	Jardiance	empagliflozin		10mg tablets	type 2 diabetes	Boehringer	Sept. 20, 2017
10		pemetrexed		100mg IV injection	anticancer	Sichuan Huiyu Pharmaceutical Co. Ltd	Sept. 29, 2017
				500mg
11	Viekirax	ombitasvir, paritaprevir ritonavir		fixed dose combo tablets	hepatitis C	Abbvie	Sept. 20, 2017
12	Tagrasso	osimertinib		40mg tablets	NSCLC	AstraZeneca	March 22, 2017
				80mg
13	Brintellix	vortioxetine			severe depression	Lundbeck	Dec. 2017
14	Lonasen	blonanserin			schizophrenia	Dainippon Sumitomo	Feb. 2017
15	Giotrif	afartinib		40mg tablets	NSCLC	Boehringer	N/A
16	Votrient	pazopanib		800mg	RCC	Novartis	March 3, 2017
17	Stivaga	regorafenib		160mg/day	CRC, GIST	Bayer	March 2017
18	Zolbrof	vemurafenib		tablets	melanoma	Roche	April 17, 2017
19	Xarelto	rivaroxaban		tablets	New PE indication	Bayer	April 2017
20	Flonase	fluticasone propionate		inhaler	expanded for use in 4-16 year-olds	GSK	Sept. 2017
21	Triumeg	abacavir, dolutegravir, lamivudine		tablet	Anti-HIV	GSK	Aug 2017
22	Xeljanz	tofacitinib		5mg tablet	RA	Pfizer	March 8, 2017
23	Myozyme	aglucosidase alfa		injection	Pompe's Disease	Sanofi	Sept 2017
24	Xolair	omalizumab		subcutaneous	atopic asthma	Novartis	Aug 2017
25	Jakavi	ruxolitinib		tablet	PMF	Novartis	March 10, 2017
26	Ebola Vaccine	recombinant		injection	Ebola infection	CanSino, China Military Med Academy	Oct. 19, 2017

(Source: CFDA, compiled by Pink Sheet)