Innovation

Was 2016 as bad a year for pharma R&D innovation as everyone says?

Each year, IDEA Pharma produces its Productive Innovation Index, designed to highlight innovation at a clinical, regulatory and commercial level within pharma.

The 2017 PII will be available in February and we’ve taken the opportunity in this article to highlight and discuss areas of interest around R&D and drug approvals.

Question, what is the meaning of the following statement?

Last year (2015) saw a large fall in the number of drugs licensed by the FDA (22) from the numbers recorded in the two previous years (41 in 2015, 45 in 2015).

Note: This includes new molecular entities (NMEs) approved by CDER (except imaging agents), plus rDNA agents approved by CBER (source: FDA)

Is it a sign of falling innovation in Pharma, a more rigorous response from the FDA, a mere statistical blip or recession to the norm (approvals of 20+ a year were common in the last decade as shown below)?

ABOVE DATA TO Dec 9th, 2016 Multiple applications pertaining to a single new molecular/biologic entity are only counted once. Original BLAs that do not contain a new active ingredient are excluded. Since applications are received and filed throughout a calendar year, the filed applications in a given calendar year do not necessarily correspond to an approval in the same calendar year. Certain applications are within their 60-day filing review period and may not be filed upon completion of the review. (Source: FDA)

NOTE: See end of this document for the complete list of 2016 FDA approvals

We can discount a more rigorous FDA as no major procedural changes have occurred according to the agency. However, contrasting this with the fact that the number of drugs submitted in 2016 was close to those in the 2 previous years, implies a fall-off in the quality of submission.

This is supported by the marked increase in applications that met with a complete response letter, the means by which the agency places a hold on application until data/ issues highlighted in the CRL are supplied or resolved. The FDA reported on Dec. 9 that 12 BLA/NME applications resulted in a CRL in 2016, compared to just two the previous year.

Is this is a measure for “the need for speed”, i.e. a rush to get to get to market? Certainly, as the table below shows, licensed drugs made increased use in 2016 of the accelerated programs available but there are insufficient data available, as yet, to suggest that failed submissions may be related to accelerated programs, although it remains an intriguing topic for investigation.

Drugs approved in 2015 and 2016

Looking at other metrics, it is hard to determine any other reason as many of the metrics used to assess drug R&D did not change significantly:

  • Research spending, now at $154 billion across the industry, has kept growing, if modestly
  • The 13 historic big pharma companies received 36% of the approvals vs. 41% in 2015
  • In both years, the same percentage of drugs (41%) were prized first-in-class therapies targeting novel modes of action
  • Cancer, infectious diseases, hematology and central nervous systems remained the leading therapeutic areas, accounting for 73% of the approvals vs. 71% in 2015
  • Biological drugs gathered a majority of the approvals for the first time (55% vs. 39% in 2015), extending the trend of recent years

To summarize, the class profile of 2016 does not stand out from its predecessor on any metric that might explain the lower approvals. It must be pointed out importantly though that 5 approvals originally slated for early 2016 were brought forward and received approval at the end of 2015, changing the approvals for 2014-2016 from 41, 45, 22 to 41, 40, 27.

What did change, however, were the companies getting the approvals. The outperformers of recent years, GlaxoSmithKline (GSK), Johnson & Johnson and Novartis did not get an approval in 2016.

Neither did Amgen, AstraZeneca, Bayer and Bristol-Myers Squibb (BMS). In all, seven of the 13 historic big pharma companies, which received 14 approvals in 2015, came up empty-handed in 2016. The remaining six companies saw their take grow from 6 to 8.

That innovation is being driven increasingly by smaller, more agile companies, was highlighted by the performance of the top 10 pharma giants, which account for about $70 billion in annual R&D (some 46% of the industry total) costs and maintain a dominant position in late-stage development, scored only eight OKs. Eli Lilly, Merck and Roche accounted for six of those. Sanofi and Pfizer each got one.

Highlights of the year included Gilead’s introduction of the first agent to treat all 6 Hepatitis C genotypes, as well as agents from the likes of Jazz Pharma and Amgen/ Biogen in orphan diseases with huge unmet needs.

We cannot leave 2016, however, without referring to the latest in the long line of agents which have fallen over in Alzheimer’s, solanezumab from Lilly. Shares in Lilly were down 14% by November and Lilly has said it would take a $150 million charge in the fourth quarter as a result of the setback, although this is clearly only a fraction of its total spend of a drug which entered Phase 2 nearly a decade ago.

Note that IDEA Pharma’s Productive Innovation Index, and its accompanying White Paper, explore the performance of individual companies in much greater detail.

Please email info@ideapharma.com to ensure that these documents are e-mailed to you immediately on publication.

What then for 2017?

Two factors argue strongly for a return to 2014-5 approvals in the coming year:

  1. The uplift in NME applications made in the second half of 2016, slated for review in 2017?
  2. The large number of complete response letters issued in 2016 will see NMEs returning to approval table with improved submissions

In addition, 2 governmental/ legislative changes may have a major impact on the FDA and the approval process:

  1. The introduction of the 21st Century Cures Act, a major new piece of legislation passed in December 2016 The act contains a very broad range of measures across research funding and drug regulation, but its core proposition is that the FDA’s process for approving new drugs and devices needed to be accelerated.
  2.  President-elect Trump has hinted at regulatory changes in the year ahead to cut through approvals red tape, and is also believed to be considering a shortlist of (inevitably) controversial candidates to be the next FDA Commissioner – with present incumbent Robert Califf almost certain to be replaced Much of Trump’s campaign message was built upon undoing much of the groundwork laid by his predecessor –  this extends to the Affordable Care Act Reducing regulatory burden on business is also part of Trump’s broader agenda, and hence his goal of perceived bottlenecks involved in the FDA’s drug approvals process While perhaps encouraging, it is important to note that references made to “cutting red tape” in President-elect Trump’s 100-day action plan were in passing at best, no specific details regarding an approach were given

In terms of approvals, the most awaited regulatory event of 2017 is probably KTE-C19 from Kite, which promises to be the first-in-class CAR-T drug approval. If its supporters are to be be believed, this will herald truly individualized cancer therapy on a realistic scale and form a genuinely new approach to treating cancer.

FDA Published List of Approvals in 2016

No. 

Drug

Company

Active Ingredient

Approval Date 2016

FDA-approved use on approval date

1

Zepatier

Merck & Co.

elbasvir and grazoprevir

28 Jan

Chronic hepatitis C virus (HCV) genotypes 1 and 4 infections in adult patients.

2

Briviact

UCB

brivaracetam

18 Feb

To treat partial onset seizures in patients age 16 years and older with epilepsy.

3

Anthim

Elusys

obiltoxaximab

18 Mar

To treat inhalational anthrax in combination with appropriate antibacterial drugs.

4

Taltz

Lilly

ixekizumab

22 Mar

To treat adults with moderate-to-severe plaque psoriasis.

5

Cinqair

Teva

reslizumab

23 Mar

To treat severe asthma

6

Defitelio

Jazz

defibrotide sodium

30 Mar

Hepatic veno-occlusive disease with kidney or lung abnormalities after stem cell transplant

7

Venclexta

AbbVie

venetoclax

11 Apr

Chronic lymphocytic leukemia in patients with a specific chromosomal abnormality

8

Nuplazid

Acadia

pimavanserin

29 Apr

Hallucinations and delusions associated with psychosis in Parkinson’s disease

9

Tecentriq

Roche

atezolizumab

18 May

To treat urothelial carcinoma, the most common type of bladder cancer

10

Zinbryta

Biogen

daclizumab

27 May

Multiple sclerosis

11

Ocaliva

Intercept

obeticholic acid

27 May

To treat rare, chronic liver disease

12

Axumin

Blue Earth

fluciclovine F 18

27 May

A new diagnostic imaging agent to detect recurrent prostate cancer

13

Netspot

AAA

gallium Ga 68 dotatate

01 Jun

A diagnostic imaging agent to detect rare neuroendocrine tumours

14

Epclusa

Gilead

sofosbuvir + velpatasvir

28 Jun

To treat all six major forms of hepatitis C

15

Xiidra

Shire

lifitegrast

11 Jul

Dry eye disease

16

Adlyxin

Sanofi

lixisenatide

27 Jul

To improve glycemic control

17

Exondys 51

Sarepta

eteplirsen

19 Sep

Duchenne muscular dystrophy

18

Lartruvo

Lilly

olaratumab

19 Oct

Soft tissue sarcoma

19

Zinplava

Merck & Co.

bezlotoxumab

21 Oct

To reduce recurrence of C diff infection

20

Eucrisa

Pfizer

crisaborole

14 Dec

Mild and moderate eczema

21

Rubraca

Clovis

rucaparib

19 Dec

Ovarian cancer

22

Spinraza

Biogen

nusinersen

23 Dec

Spinal muscular atrophy (SMA)