Pharma R&D Annual Review 2018 Supplement: New Active Substances Launched During 2017 - Pharma Intelligence
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Pharmaprojects
Pharma intelligence |
Pharma R&D Annual
Review 2018 Supplement:
New Active Substances
Launched During 2017
Ian Lloyd, Senior Director
Pharmaprojects & Data Integration
Introduction
Following on from our review of trends in the current – developing drugs is difficult. Just as in the pop
pharmaceutical R&D pipeline, published in March world, there is no formula to follow that can
2018 (visit https://pharmaintelligence.informa.com/ guarantee success. Surely world-dominating pop
resources/product-content/pharma-rd-annual- acts such as Adele, Beyoncé and Coldplay would
review-2018 to download the report for free), this agree that producing a hit is not as easy as A-B-C.
supplement takes a look at the industry’s success I suspect that even the inescapable and seemingly
stories of 2017 – the drugs which were launched on unstoppable Ed Sheeran must wonder whether, as
to the market for the first time during the year. Our he sits down to pen a new song, that, just maybe,
survey focuses exclusively on new active substances this one won’t garner the usual 2 billion Spotify
(NASs): new chemical or biological entities where streams. The pharma industry’s labs are littered with
the active ingredient had received no prior approval failures, just as the recording studio reverberates
for human use. This will include vaccines with to rejected riffs and half-realised ideas. While
novel antigenic components. As such, this list drug development is less prone than music to be
represents a subset of all the first launches which blown off-course by the vagaries of fashion, it is
Pharmaprojects reported during 2017, excluding still something of an art, or at least a very inexact
the 60 new drug launches with reformulated or science.
non-NAS moieties, or biosimilars. So to continue our
musical theme this year, we will be favouriting the But we are here to celebrate those that made it to
year’s new hit original compositions on our mp3 the top of the charts, whether they be the global
player, while skipping past the remastered reissues megahits, or are pushing forward the boundaries
(drug reformulations) and cover versions (generics of the niche genres of rare diseases. Let’s start by
and biosimilars). looking at the numbers. As our main report noted
earlier this year, R&D pipeline sizes continue to
A recent report from the consultancy Deloitte expand, which is only a good thing if output does
estimated that the financial return on drug R&D too. Well, this year, there are plenty of reasons for
across 12 large cap biotechs and pharmas fell to pharma execs to be whistling a happy tune.
just 3.2% in 2017.1 No-one can be in any doubt
1. Deloitte (2017) A new future for R&D? Measuring the return from pharmaceutical innovation 2017. Available from: https://www2.deloitte.com/uk/en/
pages/life-sciences-and-healthcare/articles/measuring-return-from-pharmaceutical-innovation.html [Accessed 20 March 2018].
© Informa UK Ltd 2018 (Unauthorized photocopying prohibited.) March 2018 / 3
54 New Active Substance Launches
Now that’s what I call music to pharma’s ears
Figure 1 shows the number of new active a noticeable dip in productivity in 2016. The NASs
substances launched by year for the millennium in this year’s veritable boxset of chart entries
thus far. The graph demonstrates clearly why 2017’s break down into 47 new chemical or biological
results are much more a polyphonic spree than entities, along with a further seven vaccines which
plaintive solo: it was the second-best year we’ve incorporate novel components. The figures add
seen, with a full 54 NAS launches. Only 2014’s 63, to a picture of this decade being a considerable
which was fuelled by a profusion of new hepatitis improvement on the noughties, where the average
C virus (HCV) therapies, beats them. This is an from 2000–09 was just 32 NASs. The mean from
excellent result for the industry, especially following 2010–17 is up to just over 46.
Figure 1: Number of NAS launches by year, 2000–17, with numbers excluding vaccines also shown
70
6
60
7
50 11
3
6 8
7
3
40
Drug Count
11 1
0
1
2 3
0 4
30
1 57
1 47
43
20
37 36 36 37 37
35 34
31
29 29 28
26 26 26
22
10
0
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
Other NASs Vaccines
Source: Pharmaprojects®, March 2018
4 / March 2018 © Informa UK Ltd 2018 (Unauthorized photocopying prohibited.)
The 2017 NAS Statistics
Big pharma gets its voice back, with cancer striking a major chord
Let’s now dive into the full tracklist of 2017’s precise indications for which they were approved,
new active substances. Table 1 provides a full their mechanism of action, the country and month
alphabetical list of the drugs, along with their trade of first launch, and indications of whether or not
names, the companies involved in their launch, the they are first-in-class and orphan drugs.
Table 1: New active substance launches, 2017
Country Month First Orphan
Trade Mechanism Of
Drug name Company Indication Of First Of First In Drug
Name Action
Launch Launch Class? Status?
Gastroenteropancreatic
neuroendocrine tumours,
Advanced
177-Lu-DOTA- unresectable or metastatic, Somatostatin
Lutathera Accelerator Denmark November N Y
octreotate progressive, well receptor agonist
(Novartis)
differentiated somatostatin
receptor positive
Postmenopausal women with Parathyroid
Ipsen/Radius
abaloparatide Eladynos osteoporosis at high risk for hormone receptor USA April N N
Health
fracture 1 agonist
Cancer, breast, hormone
receptor (HR)-positive, human
epidermal growth factor
Cyclin-dependent
abemaciclib Verzenio Eli Lilly receptor 2 (HER2)-negative USA October N N
kinase 4/6 inhibitor
advanced or metastatic
disease, after progression on
endocrine therapy
Cancer, lymphoma, mantle Bruton’s tyrosine
acalabrutinib Calquence AstraZeneca USA November N Y
cell kinase inhibitor
Infection, varicella zoster DNA helicase
amenamevir Amenalief Maruho Japan September Y N
virus inhibitor
autologous
corneal epithelial Holostem Terapie Corneal injury, Limbal stem
Holoclar Not applicable UK November N Y
cells, Holostem Avanzate/Chiesi cell deficiency
Holoclar
Metastatic merkel cell
Merck KGaA/ carcinoma in adults and
avelumab Bavencio PD-L1 antagonist USA March N Y
Pfizer paediatric patients aged 12yr
and older
© Informa UK Ltd 2018 (Unauthorized photocopying prohibited.) March 2018 / 5Country Month First Orphan
Trade Mechanism Of
Drug name Company Indication Of First Of First In Drug
Name Action
Launch Launch Class? Status?
Relapsed or refractory large
B-cell lymphoma after two
or more lines of systemic
therapy, including diffuse
large B-cell lymphoma not
axicabtagene otherwise specified, primary
Yescarta Gilead Sciences CD19 antagonist USA October N Y
ciloleucel mediastinal large B-cell
lymphoma, high-grade B-cell
lymphoma, and DLBCL arising
from follicular lymphoma
(transformed follicular
lymphoma)
Adults with moderate-to-
severe active rheumatoid
Incyte arthritis who have responded
Janus kinase 1/2
baricitinib Olumiant Corporation/Eli inadequately to, or who The EU April N N
inhibitor
Lilly are intolerant to, one or
more disease-modifying
antirheumatic drugs
Kyowa Severe asthma aged 12yr Interleukin
benralizumab Fasenra Hakko Kirin/ and older with an eosinophilic 5 receptor USA November Y N
AstraZeneca phenotype antagonist
RNA directed
Infection, hepatitis B virus, South
besifovir Besivo LG Chem/Ildong DNA polymerase November N N
chronic Korea
inhibitor
Bristol-Myers
Infection, Clostridium difficile Clostridium difficile
bezlotoxumab Zinplava Squibb/Merck USA February Y N
prophylaxis toxin B inhibitor
& Co
Anaplastic
Anaplastic lymphoma kinase- lymphoma kinase
positive (ALK+) metastatic inhibitor,
brigatinib Alunbrig Takeda non-small cell lung cancer ROS receptor USA May N Y
after progression on, or are tyrosine kinase
intolerance to, crizotinib inhibitor,
EGFR antagonist
Formycon/ Keratitis, neurotrophic; Nerve growth
cenegermin Oxervate Germany November N Y
Dompe moderate to severe factor agonist
Tripeptidyl
Late infantile neuronal ceroid Argentina
cerliponase alfa Brineura BioMarin peptidase I May Y Y
lipofuscinosis type 2 & USA
stimulant
Non-Hodgkin’s lymphoma
and relapsed or refractory
copanlisib Aliqopa Bayer follicular lymphoma in PI3 kinase inhibitor USA September N Y
patients who have received at
least two prior therapies
Phosphodiesterase
crisaborole Eucrisa Pfizer Eczema, atopic USA May N N
4 inhibitor
6 / March 2018 © Informa UK Ltd 2018 (Unauthorized photocopying prohibited.)Country Month First Orphan
Trade Mechanism Of
Drug name Company Indication Of First Of First In Drug
Name Action
Launch Launch Class? Status?
diphtheria + Infection, pertussis
pertussis + prophylaxis, Infection,
Boostagen BioNet-Asia Immunostimulant Thailand May N N
tetanus vaccine, diphtheria prophylaxis,
BioNet-Asia Infection, tetanus prophylaxis
Infection, pertussis
prophylaxis, Infection,
diphtheria prophylaxis,
Infection, tetanus
DTwP-HepB- prophylaxis, Infection,
Hib-IPV vaccine, Easysix Panacea Biotec pertussis prophylaxis, Immunostimulant India March N N
Panacea Biotec Infection, hepatitis B virus
prophylaxis, Infection,
Haemophilus influenzae
prophylaxis, Infection, polio
prophylaxis
Eczema, atopic, moderate to
severe in adults which is not
Interleukin
Regeneron/ adequately controlled with
dupilumab Dupixent 4/13 receptor USA April Y N
Sanofi topical prescription therapies,
antagonist
or when those therapies are
not advisable
Cancer, bladder, locally
advanced or metastatic
urothelial carcinoma
following disease progression
during or following platinum-
durvalumab Imfinzi AstraZeneca PD-L1 antagonist USA May N N
containing chemotherapy or
within 12mth of platinum-
containing chemotherapy
before (neoadjuvant) or after
(adjuvant) surgery
Ebola Zaire
Tianjin CanSino Infection, Ebola virus
vaccine, Tianjin Ad5-EBOV Immunostimulant China October N N
Biotechnology prophylaxis
CanSino^
Non-nucleoside
HIV/AIDS infection/ reverse
elsulfavirine Elpida Viriom Russia October N N
prophylaxis transcriptase
inhibitor
Factor IXA
emicizumab Hemlibra Roche Haemophilia A inhibitor, USA November Y Y
Factor X inhibitor
Cancer, leukaemia, acute
Agios myelogenous, relapsed or Isocitrate
enasidenib Idhifa Pharmaceuticals/ refractory disease with an dehydrogenase 2 USA August Y Y
Celgene isocitrate dehydrogenase-2 inhibitor
(IDH2) mutation
© Informa UK Ltd 2018 (Unauthorized photocopying prohibited.) March 2018 / 7Country Month First Orphan
Trade Mechanism Of
Drug name Company Indication Of First Of First In Drug
Name Action
Launch Launch Class? Status?
BioCryst
Cancer, lymphoma, T-cell, Purine nucleoside
forodesine Pharmaceuticals/
Fodosine peripheral, relapsed/ phosphorylase Japan August Y Y
hydrochloride Mundipharma
refractory disease inhibitor
International
HCV nonstructural
protein 5A
glecaprevir* +
Maviret AbbVie Infection, hepatitis C virus inhibitor, USA August N N
pibrentasvir*
HCV nonstructural
protein 3 inhibitor
MorphoSys/
Interleukin 23
guselkumab Tremfya Johnson & Psoriasis USA July N N
antagonist
Johnson
influenza vaccine, Protein Sciences/
Infection, influenza virus
quadrivalent, Flublok-Q Sanofi/ Immunostimulant USA November N N
prophylaxis
Protein Sciences ADImmune
Cancer, leukaemia, acute
inotuzumab The UK
Besponsa Pfizer lymphocytic, relapsed or DNA inhibitor August N Y
ozogamicin and USA
refractory B-cell precursor
Prostaglandin
F2 alpha and FP
latanoprostene NicOx/Valeant
Vyzulta Glaucoma receptor agonist, USA December N N
bunod Pharmaceuticals
Nitric oxide
stimulant
Infection, cytomegalovirus
prophylaxis, in adult CMV-
AiCuris/Merck CMV terminase
letermovir Prevymis seropositive recipients [R+] of USA December Y Y
& Co. inhibitor
an allogeneic hematopoietic
stem cell transplant
Melinta
meropenem + Complicated urinary tract Lactamase
Vabomere Therapeutics/ USA November N N
vaborbactam* infections inhibitor
Rempex
Cancer, leukaemia, acute
myelogenous, newly
diagnosed, FMS-like tyrosine
kinase 3 mutation-positive
(FLT3+), Mastocytosis,
advanced systemic Protein kinase C
midostaurin Rydapt Novartis USA May N Y
mastocytosis, aggressive inhibitor
systemic mastocytosis,
systemic mastocytosis with
associated hematological
neoplasm and mast cell
leukemia
Shionogi/Purdue Opioid receptor
naldemedine Symproic Constipation, opioid-induced Japan June N N
Pharma antagonist
8 / March 2018 © Informa UK Ltd 2018 (Unauthorized photocopying prohibited.)Country Month First Orphan
Trade Mechanism Of
Drug name Company Indication Of First Of First In Drug
Name Action
Launch Launch Class? Status?
EGFR kinase
Cancer, breast, adult patients inhibitor,
Puma with early stage HER2- ErbB-2 tyrosine
neratinib Nerlynx USA July Y N
Biotechnology overexpressed/amplified kinase inhibitor,
disease ErbB-4 tyrosine
kinase inhibitor
Epithelial ovarian, fallopian
tube, or primary peritoneal ADP ribose
Merck & Co./
niraparib Zejula cancer; in a complete or polymerase 1 /2 USA April N Y
Tesaro
partial response to platinum- inhibitor
based chemotherapy
Relapsing forms of multiple
sclerosis (MS) and primary
ocrelizumab Ocrevus Roche/Biogen CD20 antagonist USA March N N
progressive multiple sclerosis
(PPMS)
Synergy Constipation, chronic, Guanylate cyclase
plecanatide Trulance USA March N N
Pharmaceuticals idiopathic stimulant
rabies vaccine,
Serum Institute
Serum Institute of Rabivax-S Infection, rabies prophylaxis Immunostimulant India October N N
of India
India-2
Breast cancer, hormone-
receptor positive, human
epidermal growth factor
Otsuka
receptor-2 negative Cyclin-dependent
ribociclib Kisqali Pharmaceutical/ USA March N N
(HR+/HER2-) advanced kinase 4/6 inhibitor
Novartis
or metastatic disease,
in combination with an
aromatase inhibitor
Arthritis, rheumatoid, adult Interleukin
Regeneron/
sarilumab Kevzara patients with moderately to 6 receptor Canada February N N
Sanofi
severely active RA antagonist
sebacoyl
dinalbuphine Lumosa Moderate to severe post- Opioid kappa
Naldebain Taiwan August N N
ester, Lumosa Therapeutics operative pain receptor agonist
Therapeutics
HCV nonstructural
protein 3 inhibitor,
sofosbuvir + HCV nonstructural
velpatasvir + Vosevi Gilead Sciences Infection, hepatitis C virus protein 5B USA July N N
voxilaprevir* inhibitor,
HCV nonstructural
protein 5A inhibitor
© Informa UK Ltd 2018 (Unauthorized photocopying prohibited.) March 2018 / 9Country Month First Orphan
Trade Mechanism Of
Drug name Company Indication Of First Of First In Drug
Name Action
Launch Launch Class? Status?
Carcinoid syndrome,
in combination with
Lexicon somatostatin analogue Tryptophan 5
telotristat Xermelo Pharmaceuticals/ (SSA) to treat carcinoid hydroxylase USA March Y Y
Ipsen syndrome diarrheoa in adults inhibitor
inadequately controlled by
SSA therapy
Cancer, leukaemia, acute
lymphocytic, paediatric and
tisagenlecleucel-t Kymriah Novartis for patients up to 25 years CD19 antagonist USA October Y N
of age with B-cell precursor
acute lymphoblastic leukemia
Cancer, renal, first line
treatment of patients who are
vascular endothelial growth
Kyowa Hakko VEGFR-1,-2,-3
factor receptor and mTOR
tivozanib Fotivda Kirin/AVEO/EUSA tyrosine kinase Germany November N Y
pathway inhibitor-naive
Pharma inhibitor
following disease progression
after one prior treatment with
cytokine therapy
TissueGene/
Transforming
Kolon Life South
tonogenchoncel-L Invossa Arthritis, osteo, knee growth factor beta June Y N
Science/ Korea
1 agonist
Mundipharma
Vesicular
Neurocrine monoamine
valbenazine Ingrezza Dyskinesia, tardive, adults USA April N N
Biosciences transporter 2
inhibitor
Infection, varicella zoster
Varicella zoster
Shingrix GlaxoSmithKline virus prophylaxis, in adults Immunostimulant USA November N N
vaccine, GSK-2
aged 50yr and older
Varicella zoster
Infection, varicella zoster South
vaccine, SK Skyzoster SK Holdings Immunostimulant December N N
virus prophylaxis Korea
Chemicals
Secondary
Amgen/Ono Calcium-sensing
velcalcetide Parsabiv hyperparathyroidism in Japan February N N
Pharmaceutical receptor agonist
patients on hemodialysis
Beta-
Ultragenyx Mucopolysaccharidosis VII in
vestronidase alfa Mepsevii glucuronidase USA November Y Y
Pharmaceutical children and adults
stimulant
* = drug which is a NAS in a combo
^ = stockpiled for emergency use in case of outbreak
Some months may be approximations
Source: Pharmaprojects®, March 2018
10 / March 2018 © Informa UK Ltd 2018 (Unauthorized photocopying prohibited.)As well as being a good year in general, it was a able to report that last year, all of them launched
much better year for pharma’s stadium acts, the at least one NAS. Table 2 lists the top companies
Top 10 companies by pipeline size. 2016 had posted by number of NAS launches for all of these Top
a somewhat woeful performance, with six of the 10 companies, plus any other companies which
Top 10 unable to deliver any drugs to the market at were involved in the introduction of more than one
all. This state of affairs would surely have become therapeutic.
unsustainable, so it’s extremely good news to be
Table 2: Top company NAS launch performance, 2017
Company Number of NAS launches 2017 Position by pipeline size in Top 100
Novartis 4 1
AstraZeneca 3 3
Pfizer 3 4
Merck & Co 3 7
Sanofi 3 8
Roche 2 5
Gilead 2 24
Kyowa Hakko Kirin 2 34
Regeneron 2 75
Johnson & Johnson 1 2
GlaxoSmithKline 1 6
Takeda 1 9
Bristol-Myers Squibb 1 10
Source: Pharmaprojects®, March 2018
The table shows that last year, not only did Novartis launched more than one NAS, the firm with the best
have the biggest pipeline, it managed to launch NAS to pipeline size ratio was Regeneron, ranked at a
the most drugs, with four. It’s interesting to take a lowly number 75 by R&D portfolio. In fact, both of its
deeper dive into how it came across these agents. launches came via its long-standing collaboration on
It would seem that one was wholly originated at antibody development with Sanofi, which, prior to
the Swiss firm (Rydapt), one came via an acquisition last year, had already delivered the PCSK9 inhibitor
(Lutathera, from Advanced Accelerator), one was for high cholesterol, Praluent (alirocumab). However,
licensed-in (Kisqali, from Otsuka), and one was Sanofi is winding the development partnership down
developed in-house but used technology licensed-in now, having concluded that not only can it make
from a combination of an academic institution and its own antibodies, but also that it is keen to show
a couple of small biotechs (Kymriah). This would it is not dependent on third parties to produce new
certainly indicate that flexibility and a combination drugs.
of approaches is key to success in today’s industry.
Only two other non-Top 10 companies generated
Four other Top 10 companies were able to produce more than one NAS. Japanese venture Kyowa Hakko
three releases apiece: AstraZeneca, Pfizer, Merck & Kirin beat all of its larger compatriots by launching
Co, and Sanofi. Of the four further companies which two new agents: Fasenra for asthma and Fotivda
© Informa UK Ltd 2018 (Unauthorized photocopying prohibited.) March 2018 / 11for renal cell carcinoma. And Gilead completed its of the total, cancer’s NASs took up roughly the
successful album of hepatitis C therapeutics with same proportion of the year’s drug introductions
the triple combination drug Vosevi, which includes as it did of the development pipeline as a whole.
the NAS voxilaprevir; as well as launching the novel Anti-infectives came in a close second, with 16.
CAR-T cell therapy Yescarta – about which, more Even leaving aside the fact that this includes seven
later. vaccines, this is a more than respectable result
for this category, bolstered primarily by antiviral
When we slice up the NASs by the therapeutic area introductions. Viral therapy has come a long
of their launched indication, as Figure 2 illustrates, way in the past couple of decades, although the
the pre-eminence of cancer becomes clear. It led increasingly needed new antibacterials are still
the way in 2017 with 17 NASs launched. At 31% failing to materialize.
Figure 2: 2017 NAS launches by therapeutic group
1
2
Alimentary/Metabolic
5 1
3
Blood & Clotting
4 4 Dermatological
1
Hormonal
Anti-infective
Anticancer
Musculoskeletal
17
16
Neurological
Respiratory
Sensory
Source: Pharmaprojects®, March 2018
12 / March 2018 © Informa UK Ltd 2018 (Unauthorized photocopying prohibited.)Elsewhere, the therapeutic area with the second- So what was the country of choice for this year’s
largest pipeline, neurologicals, fared less well, with batch of new launches? It seems as though, just
just three launches. These were in multiple sclerosis, as in the music biz, the US market is the one to
pain, and tardive dyskinesia, so there were no break. As Figure 3 shows, 34 of the 54 NASs, or 63%,
advances in the big, poorly served areas such as made their debuts there. The next most popular
Alzheimer’s disease or schizophrenia. And there was NAS launching pad was Japan, with just four.
not a single NAS launch in one therapeutic area, This showcases America’s increasing dominance,
cardiovascular, and just one in the related blood and but also reflects the fact that the US FDA had a
clotting field. In terms of the types of drugs brought particularly good year in 2017, hitting a 21-year
to the market, biological drugs accounted for 24 high, with 46 approvals. Since a number of drugs
(44%) of the launches, again fairly close to the which were expected to be approved in the first
percentage in the overall pipeline. This breaks down quarter of 2018 actually made it through a quarter
into nine monoclonal antibodies, seven vaccines, earlier, it’s entirely possible that the good showing
four cell therapies, three recombinant proteins, and made by 2017 may adversely impact 2018’s
one antibody-drug conjugate. numbers – we’ll have to wait and see.
Figure 3: 2017 NAS launches by region
1 1 1 USA
1
1
1 Japan
1
1
South Korea
2
Germany
2
India
2
Canada
3 34 Denmark
EU
4
UK
Argentina
China
Russia
Taiwan
Thailand
Source: Pharmaprojects®, March 2018
© Informa UK Ltd 2018 (Unauthorized photocopying prohibited.) March 2018 / 13It’s often said that pharma is currently obsessed do nothing to dispel this impression. 19 of 2017’s
with chasing the golden goose of rare diseases, NASs received orphan drug status, up from 15 the
where although patient numbers are small, rewards year before, although percentage-wise, this is just
can be significant due to the high prices which can slightly lower than last year’s proportion, as Figure 4
be charged. A look through this year’s NAS list would shows.
Figure 4: Percentage of NAS launches with an orphan drug designation, 2012–17
60
52.2
50
40
36.1 37.0
35.2
% ODS
30
27.5 27.1
20
10
0
2012 2013 2014 2015 2016 2017
*2016 and 2017 figures refer only to drugs with orphan drug status for their marketed indication in their marketed country.
Source: Pharmaprojects®, March 2017
14 / March 2018 © Informa UK Ltd 2018 (Unauthorized photocopying prohibited.)The Novel NASs of 2017
Pharma’s musical palette broadens in a year of notable firsts
Based on the strict definition of novelty as being launch has been delayed to the first quarter of
the first time a drug with a particular mechanism this year: Spark Therapeutics’ Luxturna (voretigene
of action hits the market, 2017 produced 14 novel neparvovec). This became the first ever US-approved
NASs, up from nine in 2016. But, like any good in vivo gene therapy, targeting patients with the
DJ, we are going to have to ‘remix’ our definition ophthalmological genetic disorder, confirmed
somewhat this year to keep up with the times. This biallelic RPE65 mutation-associated retinal
is because two of the most significant launches of dystrophy. It will have to wait to take its applause
2017 were the first two chimeric antigen receptor after the encore in next year’s report, but deserves
T-cell (CAR-T) therapies. CAR-T is effectively an ex props for its contribution to a year where some of
vivo gene therapy, whereby T-cells are removed the new therapeutic techniques certainly came of
from the body and genetically modified to express age.
a CAR, which will programme the cell to target
antigens expressed on the surface of a tumour. This A further cell therapy entrant is Holoclar, Holostem
directs the T-cells, once they are introduced to the and Chiesi’s autologous corneal epithelial cell
recipient, with the specificity seen with monoclonal transplant therapy. Being a non-genetically
antibodies. Both of the first two CAR-T cell therapies manipulated whole cell transplant consisting of
to reach the market use this approach to engineer cells expanded ex vivo, it doesn’t have a specific
a patient’s own cells to target the CD19 molecule, mechanism of action as such, so once again doesn’t
which is expressed on a variety of tumours. While, count as novel by our traditional definition. However,
strictly speaking, Amgen got there first in 2014 with it’s undeniably innovative, being given the go-ahead
the CD19-targeting monoclonal antibody Blincyto in the EU back in 2015 for corneal injuries such as
(blinatumomab), there can be no denying the burns to the eye which result in limbal stem cell
intrinsic novelty of the CAR-T approach, so it feels deficiency. The UK’s health technology assessment
right to include these two ‘drugs’ in the setlist of agency, NICE, gave the green light for its use on the
2017’s most innovative hits. NHS in August 2017, but restricted its use to treating
one eye, and in those who have already had a
First to get the FDA nod was Novartis’s Kymriah conjunctival limbal autograft or there is not enough
(tisagenlecleucel-t), which was approved in August tissue for a conjunctival limbal autograft (or it is
before an October launch for paediatric acute contraindicated). It’s another orphan drug launch.
lymphocytic leukaemia and for B-cell precursor
acute lymphoblastic leukaemia in patients up to An additional ex vivo gene therapy was also
25 years of age. The CAR-T song soon became a launched, however, which manages to tick the
duet, being joined on the mic in October by Gilead boxes of being novel both in approach and via its
Sciences’ (via its Kite Pharma acquisition) Yescarta assigned mechanism of action. TissueGene and
(axicabtagene ciloleucel), which gained approval Kolon Life Science’s Invossa (tonogenchoncel-L)
in adult patients with relapsed or refractory large consists of primary chondrocytes infected with a
B-cell lymphoma for use after two or more lines retroviral vector expressing transforming growth
of systemic therapy. Both drugs received orphan factor beta 1 (TGF-ß1), which are then injected intra-
drug status, and both are expecting EU approvals articularly into the patient. This technique using
in the first half of this year. This kind of ex vivo gene local delivery overcomes the t1/2 and side-effect
therapy holds great promise, and there are a further limitations of systemically administered TGF-ß. This
68 such therapies in clinical trials at the time of makes it the first drug of any kind to hit the market
writing. with the mechanism of TGF-ß1 agonist, having been
launched in South Korea for osteoarthritis of the
On the subject of gene therapy, it also seems knee.
prudent to mention in passing a highly significant
2017 approval which didn’t make our list, as its This chorus of approval for cell and gene therapies
© Informa UK Ltd 2018 (Unauthorized photocopying prohibited.) March 2018 / 15has been matched in cancer by a further set of these, GlaxoSmithKline’s Shingrix, is expected to
of first-in-class drugs of the more established achieve blockbuster status.
kinds. Whereas this year, there were no such new
monoclonal antibodies, there was further activity Also novel in the bacterial infections world is
in the small molecule kinase inhibitors space. Zinplava (bezlotoxumab), for the treatment of
Launched in July by Puma Biotechnology was Clostridium difficile (C. diff) infections. This is not an
Nerlynx (neratinib), which is approved for adult antibiotic; rather, it is a monoclonal antibody specific
breast cancer patients with HER2-overexpressed/ for C. diff’s toxin B. It is this toxin which causes the
amplified disease. What makes this agent novel diarrhoea associated with this intestinal infection.
though, is that as well as targeting ErbB-2 tyrosine Originally under development by Medarex, Bristol-
kinase (HER2), it also hits the ERbB-4 kinase, or HER4. Myers Squibb acquired rights following its acquisition
of that company, but licensed it out for development
Before we leave cancer, which, aside from the and commercialization to Merck & Co. Its US launch
CAR-T therapies, accounts for only four of the in February was quickly followed by EU launches
novel NASs, there are a further two first-in-class and a Japanese approval later in the year. A follow-
orphan drugs which both debuted in August. Agios up combination product adding actoxumab, which
Pharmaceuticals and its collaborator, Celgene, targets C. diff’s toxin A, is already in Phase III trials.
premiered Idhifa (enasidenib), the first isocitrate
dehydrogenase 2 (IDH2) inhibitor, which was In the metabolic area, two new enzyme
greenlit specifically for patients suffering from replacement therapies count as first-in-class.
relapsed or refractory acute myelogenous leukaemia Late infantile neuronal ceroid lipofuscinosis type 2
with an IDH2 mutation. Finally, the combination of may be more of an obscure indie band type of
BioCryst and Mundipharma delivered the first purine disease than a headline act, but is a severe and
nucleoside phosphorylase inhibitor in the form of fatal childhood lysosomal storage disorder disease
Fodosine (forodesine hydrochloride). This drug is causing seizures, vision loss, and death usually
indicated for relapsed or refractory peripheral T-cell before the age of 12. It is caused by defective
lymphoma and is another of the NASs starting its lysosomal tripeptidyl peptidase I, something
world tour in Japan. addressed by BioMarin’s recombinant version of
the enzyme, Brineura (cerliponase alfa). Similarly,
Moving to this year’s other success story, anti- Ultragenyx Pharmaceutical’s Mepsevii (vestronidase
infectives, unusually, there were two novel NASs alfa) is a recombinant form of beta-glucuronidase,
in viral diseases in 2017 away from the usual HIV the enzyme which is faulty in another lysosomal
or HCV axis. Cytomegalovirus (CMV) is an infection storage disorder, mucopolysaccharidosis type VII.
which fell off the radar somewhat in recent years; it Unsurprisingly as both of these drugs are for very
was a common opportunistic infection in AIDS, but rare metabolic disorders, both have orphan drug
is now rarely seen in the West due to the rarity of status.
the syndrome as most HIV patients are successfully
kept in good health by antiretrovirals. However, it Moving to autoimmune diseases, two novel
can still pose a problem in other immunosuppressed monoclonal antibodies got their big break.
populations, such as those who have undergone The first interleukin-5 receptor antagonist (as
bone marrow transplants following chemotherapy. opposed to the previously launched direct Il-5
Thus, it’s good to welcome AiCuris and Merck & Co’s antagonists, mepolizumab and reslizumab), Fasenra
Prevymis (letermovir) to this year’s rock ‘n’ roll hall (benralizumab), was a codevelopment between
of fame. It’s the first example of a CMV terminase AstraZeneca and the drug’s originator, Japan’s
inhibitor, and was launched in the US at year-end Kyowa Hakko Kirin, using the latter’s proprietary
for prophylactic use in adult CMV-seropositive Potelligent technology. The indication here is severe
recipients of an allogeneic hematopoietic stem cell asthma in patients aged 12 years and older with
transplant. In Japan, we saw Maruho’s Amenalief an eosinophilic phenotype, and launch occurred
(amenamevir) introduced for varicella zoster virus in the US in November. Dupixent (dupilumab) is
infection (shingles). It’s a DNA helicase inhibitor, the first systemic therapy for atopic dermatitis to
and contributes to a banner year for shingles, with hit the market, along with being the first to have
two new vaccines also reaching the market. One the mechanisms of interleukin-4 and -13 receptor
16 / March 2018 © Informa UK Ltd 2018 (Unauthorized photocopying prohibited.)antagonism. This drug is indicated for the difficult- Roche and Biogen’s Ocrevus (ocrelizumab) for
to-treat population of adults with moderate-to- the relapsing-remitting and primary progressive
severe disease which is inadequately controlled forms of multiple sclerosis distinguished itself by
with prescription topical therapies, or where such booking almost a billion US dollars-worth of sales
therapies are deemed not advisable. The drug’s US in the nine months it was on the market – a record
launch has been followed by several in the EU, and for recent introductions. Also in the autoimmune
developers Sanofi and Regeneron have already filed area, Regeneron and Sanofi’s Kevzara (sarilumab)
a follow-on application in the US for use in asthma, is set to make a noise in rheumatoid arthritis (RA).
with an EU filing in this indication to come in 2018. It will need to pump up the volume to make itself
heard in a crowded market, which is dominated by
Antibodies are even finding their way into Roche’s Actemra (tocilizumab), but the RA market
haemophilia, a disease more commonly associated is sizeable, and patient response with therapies
with treatment via recombinant proteins. Hemlibra variable, so any chunk which it can grab will reap
(emicizumab) is an asymmetric bispecific IgG rewards. Also entering a competitive arena is
antibody to factor IXa and factor X, which mimics MorphoSys and Johnson & Johnson’s monoclonal
the factor VIII cofactor function. It can thus be for plaque psoriasis, Tremfya (guselkumab). It
used to prevent or reduce the frequency of bleeding is the first product to be launched based on the
episodes in adults and children with haemophilia A German biotech’s proprietary HuCAL antibody library
with factor VIII inhibitors. It’s also the first time technology, and is rolling out in Europe now too,
we’ve seen factor IXa inhibition as a mechanism following a July US first launch.
on an approved drug, and once again, the US is
the first market to benefit, with the EU expected But, like a 70s concept album, let’s bookend our
to be in harmony later this year. However, there is discussion with a reprisal to where we began, as
a note of dissonance to add to this refrain, as the it was indisputably cancer’s year. They may not
drug’s owner, Roche/Genentech, is facing patent be the New Kids On The Block anymore, but the
challenges from its competitor Shire. immuno-oncology strategies had another good
year, with PD-L1 antagonists having successful
Our final novel NAS, Xermelo (telotristat ethyl), is for follow-ups to Roche/Genentech’s 2016 hit Tecentriq
yet another orphan disease – diarrhoea associated (atezolizumab) in the form of both AstraZeneca’s
with carcinoid syndrome, for use in combination Imfinzi (durvalumab) and Merck KGaA and Pfizer’s
with somatostatin analogues where the latter alone Bavencio (avelumab). Both were launched in May for
proved inadequate. This syndrome is found to occur urothelial cancer, with the latter also being launched
in about 5% of patients with carcinoid tumours, a a little earlier in the year for Merkel cell carcinoma.
slow-growing form of neuroendocrine tumour, and And the more established small molecule kinase
can include intense diarrhoea, abdominal pain, and inhibitors keep on rockin’ too, with a whole host of
flushing of the skin, caused by endogenous secretion new agents. The supergroup here had AstraZeneca
of serotonin and kallikrein. As the world’s first also bringing Calquence (acalabrutinib) to the party,
tryptophan hydroxylase inhibitor, the agent works by along with Otsuka and Novartis’s Kisqali (ribociclib),
inhibiting the former’s production. It’s a new release Eli Lilly’s Verzenio (abemaciclib), Bayer’s Aliqopa
from the duo of Lexicon Pharmaceuticals and Ipsen. (copanlisib), and Kyowa Hakko Kirin, AVEO and
EUSA Pharma’s Fotivda (tivozanib). 2017’s NAS list
A few other 2017 debuts deserve a sleeve note was truly music to the ears of oncologists in their
credit, despite not being strictly-speaking novel. ongoing battle with this devastating area of disease.
© Informa UK Ltd 2018 (Unauthorized photocopying prohibited.) March 2018 / 17Good Vibrations for Pharma as it Enjoys a Second Summer of Love
But no room for complacency if a punk-style backlash is to be avoided
It would seem that the Good Times are back for Believe The Hype. The promised efficiencies to the
the pharma industry, based on the combined R&D process didn’t really materialize, with little
analyses of this year’s Pharma R&D Report and this discernible improvement in attrition rates or drug
NAS Supplement. The industry continues to grow, development times. The industry turned to the
with more drugs in the pipeline than ever before, megamerger to solve its problems in the noughties,
which seems to be delivering a healthy output of but this didn’t seem to work either, and productivity
new therapeutics and some major advances for went into something of a slump. A change of tactics
patients. But history teaches us that trends tend to was needed. The past decade has seen Big Pharma
be cyclical. So let’s draw one final analogy from the narrow its focus to fewer therapeutic areas, and
world of popular music before we close, to sound a seize on rare diseases as a route to enlightenment.
note of caution. Instead of miring itself in huge corporate mergers
and acquisitions, it is looking to bolster its pipelines
In the late sixties, a flowering of creativity and via targeted in-licensing and takeovers of smaller,
seismic societal changes led to the so-called more agile companies where innovation has
Summer Of Love. There was a feeling that anything prospered. As a result, pharma seems to be enjoying
was possible. But disillusionment soon set in, something of a second summer of love of its own.
fuelled by the Vietnam war, and the hippie ideal
and flowers in the hair soon wilted. Seventies prog But history teaches us the prudence of injecting a
rock grew self-important, bloated and complacent. few cautionary notes. As previously outlined, the
Inevitably, revolution was scented on the air. The somewhat arbitrary nature of taking a snapshot
twin blitzkriegs of punk and disco shook up the late by calendar year can serve to flatter one year at
seventies, leading to another creative flowering and the expense of the next. So a year of fanfare can
the so-called second summer of love in the late very easily be followed by a funereal dirge the
eighties, as rave culture burst through. This time, the next. Secondly, you never know when the intrinsic
riot of innovation fell to the corporate takeover, as complexities of biological systems themselves
big business moved in and created the superclubs might throw a spanner in the works. There are many
and the bombastic sounds of EDM. Arguably, we are examples of drug class effects which only show
now in an era of unsurpassed musical blandness up in late-stage development, or even worse, after
and homogeneity, but, in reality, innovation has just launch. It would only take an unexpected problem
returned to the underground. It’s all one big Circle Of to arise in a hot area, such as immuno-oncology or
Life. CAR-T, to change the industry’s mood from Ready
For The Weekend to Blue Monday. In the political
How does this relate to pharma’s fortunes? Like arena, for those Born In The USA, the capricious
Prince, it certainly had a purple patch in the late nature of the country’s president ensures that few
eighties and nineties, when there were high levels are clear as to whether he is the industry’s Friend Or
of NAS introductions, and it seemed that emerging Foe. And will instability in Europe, and in particular
technologies were also leading to a new dawn Britain following the latter’s Brexit, lead to Anarchy
and a new day, which would leave the industry In The UK? Many fear so. In a survey conducted by
Feeling Good. But it turned out to be a case of Don’t Informa Pharma Intelligence’s Scrip publication,
18 / March 2018 © Informa UK Ltd 2018 (Unauthorized photocopying prohibited.)fewer than one in six pharma executives surveyed to be highlighting next year are: three new anti-
thought that drug development in the UK would not CGRP monoclonals (a new class of drugs for
be impacted by Brexit, and 73% thought that the the prophylaxis of migraine); an endometriosis
UK will be a later market for new product launches – and uterine fibroids therapy predicted to be a
sobering stuff. Plus, novelty rates remain fragile, and blockbuster; a new therapy for moderate-to-severe
will need bolstering if the industry is to stay relevant psoriasis; and further agents in the exciting CAR-T
and not fall back on relying on drug tribute acts. and immuno-oncology franchises. Pharmaprojects
So certainly, there is no shortage of reasons why and the rest of Informa Pharma Intelligence will
pharma’s apparent progress this year could easily be continue to watch for new breakout successes,
blown off course. because as in the music industry, there is no such
thing as a dead cert. But with the pipeline currently
But to end in a major key, 2018 is looking potentially busting with hot new talent, it could well be that
exciting. Among the pending approvals we expect some of pharma’s Greatest Hits are still to come.
© Informa UK Ltd 2018 (Unauthorized photocopying prohibited.) March 2018 / 19pharma@informa.com
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