'Flexible Pricing' For Kisqali To Compete Against Pfizer

24 Pages·2017·2.58 MB·English

Company Focus Expert view Changes to NICE Timelines
Analysts aren’t surprised to see the Hemophilia patients are loyal to New rules will allow NHS England
Danish diabetes giant stalking brand-name clotting factors but a to delay some new drugs for up to
Global Blood Therapeutics (p5) shakeup may be coming (p8) three years (p15)
Scrip24 March 2017
No. 3846
scrip.pharmamedtechbi.com Pharma intelligence | informa
Novartis is looking to differentiate through
its “flexible price structure.”
Bill Hinshaw, head of Novartis US Oncol-
ogy, revealed the price structure during a
conference call with reporters on March
13, explaining that the wholesale acquisi-
tion cost (WAC) for a 28-day cycle (21 days
on treatment followed by seven days off)
is $10,950 for the 600 mg once-daily dose,
$8,760 for the 400 mg dose and $4,380
for the 200 mg dose; a patient assistance
program will be available for both insured
and uninsured patients. The drug will be
shipped to specialty and retail pharmacies
Shutterstock: Lightspring asdapsno Hodssoin inhnodgesnsh m b taaoaawss t tMeo hdlneao or ognctniheec de k s1nd i4do t.fehow aern tffp cerKeacisrstdcsq.ri aoSiblvoi eamprsscre ituc oclinaa arsg,de l ijsvur eoest-rf
QT prolongation, AST and/or ALT elevation
Novartis Sets ‘Flexible Pricing’ For and high-grade neutropenia were reported
in the Phase III MONALEESA-2 trial, which
was the basis for the US FDA approval.
Kisqali To Compete Against Pfizer
Novartis has formulated Kisqali in 200 mg
capsules, making it easier for oncologists to
MANDY JACKSON [email protected] lower dosing to the required 400 mg or 200
mg doses as needed to manage the CDK4/6
Novartis has packaged and priced Kisqali – the second CDK4/6 inhibitor approved in inhibitor’s effects on heart rhythm, liver
the US – to compete with Pfizer’s Ibrance, which made the mechanism of action the function and neutropenia – three items that
standard of care in untreated metastatic HR+/HER2- breast cancer. prescribers must measure at certain points
before and during treatment.
Novartis AG’s Kisqali (ribociclib; dent kinase 4 and 6 (CDK4/6) inhibitors. Hinshaw noted that Kisqali dosing can
LEE011) was approved on March The mechanism quickly became the front- be reduced without treatment interruption
13 as the second drug of its kind in line standard of care for post-menopausal – a luxury that oncologists don’t have with
the first-line setting for certain breast cancer women with hormone receptor (HR)- Pfizer’s Ibrance, which is formulated in 125
patients in the US – and it could have com- positive/human epidermal growth factor mg, 100 mg and 75 mg capsules and was
petition from a third next year – so the com- receptor-2 (HER2)-negative advanced or launched in early 2015 with a WAC price
pany has packaged and priced its product metastatic breast cancer – the populations per cycle of $9,850. Ibrance pricing in ex-US
to compete with Pfizer Inc.’s first-to-market for which Kisqali and Ibrance are approved. markets has come under pressure, particu-
Ibrance (palbociclib). Similar profiles for the two drugs were seen larly in the UK where its cost may limit ac-
Both drugs and Eli Lilly & Co.’s Phase III in Phase III clinical trials that were stopped cess. The drug is under review in Japan.
candidate abemaciclib are cyclin-depen- early for positive efficacy, so its appears that CONTINUED ON PAGE 7
BROUGHT TO YOU BY THE EDITORS OF PHARMASIA NEWS, START-UP AND SCRIP INTELLIGENCE
IN THIS ISSUE
5
Competition
iTeos: IO
For Hemophilia
Therapies For
Franchises
Hot And Cold
Tumors
Novo After Global
8 21
Blood Therapeutics?
COVER / Novartis Sets ‘Flexible Pricing’ For Kisqali To Compete
from the editor Against Pfizer
[email protected] 3 Mylan Clears Runway For US Herceptin Biosimilar Launch
4 Blood Cancer Sector More Competitive After
The term ‘microbiome’ has only really taken on any
Keytruda Approval
kind of currency since the early part of this century,
but in the past few years it has become a regular 5 Company Focus: Is Anemic Growth Sending
feature of biopharma discussions. Referring to the Novo Nordisk After Global Blood Therapeutics?
totality of the micro-organisms (and their genetic
6 Ackman ‘Throws In The Towel’ – What’s Next For Valeant?
material) in a particular environment, the human
microbiome (and most commonly that of the gut) is
7 Threshold/Molecular Templates: The Power Of Two
increasingly the target of therapeutic R&D programs,
and the raison d’être for a growing band of start-ups. 8 Expert View: Competition Coming For Hemophilia
We have created an infographic (p14) on the indus- Franchises, But Will Patients And Payers Embrace
try’s efforts in the field, which has attracted around New Drugs?
$1bn in company funding since 2011. As with any
11 R&D Bulletin
hot topic, there are voices of caution and dissent; one
panellist in a partnering function at a big pharma 12 Research & Development: AstraZeneca’s Lynparza
memorably declared at BIO last year that she might Looks To Hang On To Lead
herself get C. diff if yet another microbiome proposi-
13 Editas Deal Opens Allergan’s Eyes To CRISPR
tion crossed her desk.
Scrip would like to hear the views of our readers: 14 Infographic: The Microbiome
are you excited about the opportunity in this field?
15 Pricing: NICE Appraisal Changes: A New Pricing Hurdle
Or are you cautious about significant hurdles that
you feel are being overlooked? Drop me an email.
16 Business Bulletin
17 Company Focus: Lilly Eyes Top 10 Japan Ranking Built
On Launches
18 FDA Moves On Endo’s Opana ER Unlikely To Sweep
Up Other Opioids
exclusive online content
20 Policy & Regulation Briefs
21 Emerging Company Profile: iTeos: IO Therapies For
Is Amgen’s FOURIER Enough For Physicians,
Hot And Cold Tumors
Payers To Expand Repatha Use?
Detailed results presented at ACC show a reduction in risk of 22 Pipeline Watch
major adverse cardiovascular events, but perhaps not at the
23 Appointments
level hoped for by payers.
http://bit.ly/2neial5
Finance Watch: Two New VC Funds Raise $500m;
One New US IPO; And Galena’s ‘Strategic Review’
http://bit.ly/2nRAZbp
Deal Watch: Success Nets CytomX Another
$200m From BMS, Up To $3.6bn For Milestones
http://bit.ly/2nd2IVC
@scripnews /scripintelligence
/scripintelligence /scripintelligence
2 | Scrip intelligence | 24 March 2017 © Informa UK Ltd 2017
HEADLINE NEWS
Mylan Clears Runway For US Herceptin Biosimilar Launch
JESSICA MERRILL jessica [email protected]
Mylan NV could be the first manufacturer to launch a biosimilar logics Price Competition and Innovation Act’s (BPCIA) “patent dance”
version of Roche’s blockbuster breast cancer treatment Herceptin is optional or mandatory and whether 351(k) sponsors must wait until
(trastuzumab) in the US. The company has an application for a ver- licensure before providing 180-day notice of launch.
sion of trastuzumab pending at FDA with a user fee date of Sept. There has not been much legal precedent yet related to biosimi-
3., and now the company has also cleared the crucial intellectual lars in the US, so it remains to be seen how the IP issue will evolve.
property hurdle. There are many other versions of trastuzumab in development, and
there is no guarantee that Mylan’s product, developed with partner
Mylan announced March 13 that it has reached a patent Biocon Ltd., will have a smooth regulatory review. Mylan updated in-
settlement agreement and a licensing deal with Roche vestors on its pipeline during an investor overview March 1, highlight-
related to patents for Herceptin. The global license will pro- ing biosimilars and complex small molecule drugs. The company said
vide a clear path for Mylan to commercialize trastuzumab globally it has one of the broadest biosimilar pipelines in the industry, including
(excluding Japan, Brazil and Mexico), the firm said. The catch is that a second product pending at FDA, a biosimilar to Amgen’s Neulasta
the US launch timeline remains unknown. Mylan said the effective (pegfilgrastim), with an Oct. 9 action date.
dates for launches in various markets under the agreement remain There are as many as 19 different formulations of trastuzumab in de-
confidential, which means it is unclear how much, if any, delay Mylan velopment. Pfizer Inc. has completed Phase III testing of its formula and
and Roche might have negotiated beyond the FDA action date. presented positive top-line results in December.
Mylan, meanwhile, agreed to withdraw its pending inter partes re- Approved in 1998, Herceptin is a backbone therapy for the treat-
view (IPR) challenges against two US patents for Herceptin held by ment of women with HER2-positive breast cancer. Herceptin gener-
Roche’s Genentech unit (patents 6,407,213 and 6,331,415). ated CHF6.78bn ($6.73bn) in 2016. The drug is one of Roche’s top-
Biosimilar sponsors face a tangled web of patent proceedings, which sellers, behind Rituxan (rituximab) and Avastin (bevacizumab), which
are one of the biggest hurdles to getting more biosimilars to market. are also expected to face biosimilar competition, creating substantial
More clarity on the legal proceedings could come in 2017. The US headwinds for the Swiss pharma. Roche introduced an antibody-drug
Supreme Court agreed to hear a dispute between Amgen and Sandoz conjugate version, Kadcyla (ado-trastuzumab emtansine) in 2013.
Inc. involving Sandoz’s Zarxio (filgrastim) related to whether the Bio- Published online 13 March 2017
scrip.pharmamedtechbi.com 24 March 2017 | Scrip intelligence | 3
HEADLINE NEWS
Blood Cancer Sector More Competitive After
Keytruda Approval
The US FDA approval of Keytruda in its first hematologic cancer indication will put Merck & Co in a position to
compete with Bristol-Myers Squibb, whose own checkpoint inhibitor Opdivo gained a similar, but not identical,
marketing approval in classical Hodgkin lymphoma last year.
JOHN DAVIS [email protected]
Confirmation that checkpoint inhibitors are beneficial in the ing patients, the median duration of response was 11.1 months
treatment of blood-borne cancers has come from the US (ranging from zero to 11.1 months).
approval of Merck & Co. Inc.’s anti-PD1 therapy Keytruda Keytruda is administered intravenously every three weeks until
(pembrolizumab) for the treatment of patients with classical Hodg- disease progression or unacceptable toxicity, or up to 24 months in
kin lymphoma refractory to other treatments, or who have relapsed patients without disease progression. This compares with a dosing
after three or more prior lines of therapy. Previously the drug was schedule of every two weeks for Opdivo.
only approved in solid tumors. Keytruda was discontinued due to adverse reactions in 5% of 210
The approval, announced March 14, is the first for Keytruda in a patients in the KEYNOTE-087 study, and treatment was interrupted
hematologic malignancy, and Merck also highlighted that the addi- due to adverse reactions in 26% of patients. The most frequent se-
tional indication is regardless of prior stem cell transplant or use of rious adverse reactions (>1%) were pneumonia, pneumonitis, py-
Seattle Genetics Inc.’s Adcetris (brentuximab vedotin). The approval rexia, dyspnea, GvHD and herpes zoster.
comes nearly a year after Bristol-Myers Squibb Co.’s checkpoint
inhibitor Opdivo (nivolumab) was approved in the US for a similar The additional indication is regardless
indication, although then the FDA specified that Opdivo therapy
in relapsed and refractory classical Hodgkin lymphoma should of prior stem cell transplant or use of
follow treatment with autologous stem cell transplant and post-
brentuximab vedotin
transplant brentuximab vedotin therapy.
In Europe, Opdivo was approved for the classical Hodgkin lym-
phoma additional indication in November 2016, while Keytruda is There are few other options for patients with classical Hodgkin
in Phase III studies for classical Hodgkin lymphoma. lymphoma who do not respond to a stem cell transplant, or use of
Interestingly, Opdivo has just been knocked back by the UK’s brentuximab vedotin. “Treating their disease becomes more chal-
health technology assessment body, NICE, that asked in a prelimi- lenging,” commented Dr Craig Moskowitz, clinical director in the
nary assessment released March 13 for a revision of cost-effective- division of hematologic oncology at the Memorial Sloan Kettering
ness analyses versus standard of care, the use of UK data on stan- Cancer Center, in a Merck statement.
dard of care, and data on the subsequent rate of allogeneic stem There are also far fewer patients with classical lymphoma; there
cell transplant. That could allow Keytruda to catch up some ground are around 8,500 new cases reported every year in the US, with
on the BMS drug, at least in the UK. around 1,120 deaths, with the condition affecting patients at a
According to Datamonitor Healthcare senior analyst Dominique relatively young age, predominantly adolescents and young adults.
Fontanilla, the US approval is positive news for Keytruda, but is un- Fortunately, nearly three-quarters of patients are cured with che-
likely to have a major impact in terms of sales. Hodgkin lymphoma motherapy and/or radiation.
is relatively uncommon, with DMHC estimating there were 18,770 In the past, the use of checkpoint inhibitors has been primar-
diagnosed cases in 2014 in the US, Japan, and the five major EU ily focused on solid tumors such as non-small cell lung cancer.
markets (France, Germany, Italy, Spain and the UK). Additionally, However, their use in blood cancers is now an active field of
Keytruda’s and Opdivo’s approvals in the later line of treatments research, with for example Celgene Corp. and AstraZeneca PLC
means the potential market size is even smaller. partnering on the development of the PD-L1 inhibitor dur-
However, Merck has started a large Phase III study (KEYNOTE-204) valumab in hematologic cancers, and BMS studying Opdivo in
comparing Keytruda to the current standard of care Adcetris in pa- multiple myeloma.
tients with relapsed Hodgkin lymphoma, that could close any gap Merck also reported March 14 a three-month extension, to June
between Keytruda and Opdivo, Fontanilla commented. 9, 2017, to the FDA’s target action date on its sBLA for Keytruda use
Keytruda was cleared under the US’s accelerated approval regu- in previously-treated patients with advanced microsatellite instability-
lations for use in adult and pediatric patients with refractory classi- high (MSI-H) cancer. MSI-H is seen in around 15% of patients with
cal Hodgkin lymphoma (cHL), or who have relapsed after three or colorectal cancer, and Merck recently submitted additional data and
more prior lines of therapy, based on the tumor response rate and analyses to the regulator, that was considered a major amendment
the durability of that response in the KEYNOTE-087 study. In that necessitating a three-month extension to the review. Merck could be-
study involving 210 patients, the overall response rate with Key- come one of the first companies to gain an approval for a checkpoint
truda was 69% (95% CI: 62, 75) with a complete remission rate of inhibitor in colorectal cancer.
22% and a partial remission rate of 47%. Among the 145 respond- Published online 15 March 2017
4 | Scrip intelligence | 24 March 2017 © Informa UK Ltd 2017
COMPANY FOCUS
Is Anemic Growth Sending Novo Nordisk After Global
Blood Therapeutics?
STEN STOVALL [email protected]
Once high-flying Novo Nordisk has been drug emicizumab (ACE910) eroding sales
sending out M&A signals as it seeks a so- of NovoSeven, and thus acting as a drag
lution to weak growth, so analysts aren’t on 2018 and 2019 earnings.” NovoSeven
surprised to see the Danish diabetes is Novo Nordisk’s aging hemophilia drug
giant stalking US-based Global Blood whose sales have been sliding; the com-
Therapeutics. pany doesn’t yet have strong commercial
response after it decided in September
Novo Nordisk AS’s long and steady fi- 2012 to discontinue the development of
nancial run on self-generated diabe- vatreptacog alfa, a fast-acting recombi-
tes and obesity products is flagging nant Factor VIIa analogue for hemophilia
–tlriehn apaentos d rittt o stnh geietee Dndiseas r niantiotsteh er r fegervesriosttehaud lpirz e eihvn eai tnsCs u aaoeclitk fhgonerroonrw wipalt-rebhod ad–gsu eescddot pitNnilao ttPvihehoenaSnstes eva ewsII nIia t.t hrrie aipnlslha aicbneidtmo hersna dtw fhboierc ehbn loh scaekdeb nbu esutenen-r Shutterstock: Cherries
Global Blood Therapeutics Inc. have not sur-
prised observers. GLOBAL BLOOD BOLT-ON?
‘Novo Nordisk has avoided
Reuters and Bloomberg, quoting un- So could Global Blood Therapeutics help
named sources, reported the South San the Danish group respond to its current acquisitions in the past, so
Francisco-based sickle cell drug developer commercial gloom?
this is a change of direction
has been approached by Novo Nordisk. The loss-making company was found-
Neither Global Blood nor Novo Nordisk ed in 2012 by Third Rock Ventures and for them’
would comment to Scrip on the reports, launched an IPO in Aug. 2014. Before me-
but analysts say it makes sense for the Dan- dia reports of Novo Nordisk’s interest in it,
ish group to actively look outside for a bolt Global Blood Therapeutics had a market
on to help it diversify beyond its aging dia- value of around $1.2bn.
betes franchise. It is developing drugs for blood-based FDA for treating patients with SCD and or-
diseases including sickle cell disease (SCD) phan status in Europe.
DIVERSIFICATION NEEDED and idiopathic pulmonary fibrosis. Ana- “It’s an interesting approach, chang-
“I’m sure it’s a calculated risk; in this case lysts say acquiring the young company ing the affinity of hemoglobin for oxy-
since Novo Nordisk’s diabetes business is would provide positive additions to Novo gen, but the data are still somewhat
suffering, so they need to focus elsewhere Nordisk’s portfolio. Of immediate interest preliminary at this point,” BioMedTracker
and this acquisition can help them strength- is its product candidate known as GBT440, analyst Peter Chang said, adding that the
en their blood offerings. Novo has avoided a hemoglobin modifier that binds to he- drug did increase hemoglobin apprecia-
acquisitions in the past so this is a change moglobin molecules. The oral, once-daily bly “and could well impact symptoms,
of direction for them,” commented Steven therapy for sickle cell disease is in double- though the study was quite small and
Muntner of Medtrack. blind Phase I/II clinical trialing and will en- there is only limited side effect informa-
Rising competition and pricing pressures ter a pivotal Phase III study in SCD called tion so far.”
in the US and elsewhere led Novo Nordisk HOPE by the end of 2017, according to Analysts said Novo Nordisk had alerted
last October to slash its growth expecta- BioMedTracker. Like hemophilia, SCD is an the investment community last year dur-
tions for 2017 and increase R&D efforts, an- orphan disease. ing its third quarterly earnings update that
nouncing expansion into new therapy ar- Since oxygenated sickle hemoglobin it was thinking about M&A.
eas and seek external deals for early-stage does not polymerize, Global Blood Thera- “They were looking to do bolt-on acqui-
assets to bulk up its pipeline. peutics thinks GBT440 blocks polymer- sitions, which they said was more realistic
Its outlook reduction last autumn sent ization and the resultant sickling of red than a large acquisition, and get slightly
Novo Nordisk shares south. Berenberg an- blood cells. “With the potential to restore out of their core and add competencies,
alysts Mar. 6 said, “Novo’s shares have not normal hemoglobin function and improve in addition to their growth in emerging
recovered from the profit warnings issued oxygen delivery, GBT440 may be capable markets for diversification. So it does look
by the group in 2016. It is clear from guid- of modifying the progression of SCD,” the like this would fit into their strategy in that
ance that 2017 will be a slow year, and company says. GBT440 has both fast track sense,” Chang said.
there is a risk of Roche’s new hemophilia and orphan drug designation from the Published online 13 March 2017
scrip.pharmamedtechbi.com 24 March 2017 | Scrip intelligence | 5
HEADLINE NEWS
Ackman ‘Throws In The Towel’ – What’s Next For Valeant?
Valeant’s prospects were dim with or without Pershing Square’s continued backing, but at least one analyst says
Ackman’s departure sends a signal that business won’t rebound at the Canadian specialty pharma any time soon.
JOSEPH HAAS [email protected]
The business outlook at Valeant Phar- portfolio, including recently approved pso- approvals, and a primary care effort behind
maceuticals International Inc. is un- riasis drug Siliq (brodalumab). Valeant CEO key product Xifaxan to accelerate that prod-
certain at best and the sell-off by Joseph Papa expressed optimism about uct,” Nachman said.
Pershing Square Capital Management of its Siliq’s potential to be a growth-driving prod- In a March 14 note on Pershing Square
nearly 10% stake in the Canadian specialty uct for the company during its most recent Holdings, Jefferies analyst Matthew Hose
pharma doesn’t necessarily make the situa- earnings call Feb. 28, but analysts aren’t ter- suggested that with Valeant’s stock having
tion any worse – but only because Valeant’s ribly bullish on the product. fallen 95% from its peak price, the hedge
prospects are so bleak to begin with. “Unsurprisingly, Valeant’s stock seems to fund’s investors “are likely to have attribut-
Pershing Square, led by billionaire activist be reacting to the loss of [Ackman’s] vote ed little or no value to the remaining posi-
investor Bill Ackman, had tied its fortunes to of confidence, but the fundamentals of the tion in Valeant.” He expects the divestiture
Valeant in the past two years, going so far as business remain unchanged, from our per- to play out positively for Pershing Square.
to increase its holdings in the firm as a com- spective,” W aterhouse told Scrip. “Restructur-
bination of pricing pressure, accounting ing the debt maturities is a slight positive, CHOPPY WATERS
questions and a heavy debt load catalyzed but management still has a lot of work to It’s been a stormy tenure at Valeant for Ack-
an ongoing decimation of Valeant’s share do with asset sales or returning to growth man, who stage-managed the departure of
price. Ackman aligned himself with the to climb out of the debt hole. Greater than Pearson – the exec who had overseen a long
troubled biopharma, even testifying along- expected performance from Xifaxan or from string of acquisitions around already-on-
side the embattled outgoing CEO Michael the launch of Siliq could offer some upside, market products or late-stage clinical can-
Pearson before the Senate Aging Commit- but we’re skeptical for the time being.” didates to build up the company’s portfolio
tee about the company’s practices last April. In a March 6 note on Valeant, Waterhouse – and his replacement with Papa, former
All that changed March 13, as Pershing had said the specialty firm faces an exacer- CEO of Perrigo Co. PLC. The Senate Aging
Square Holdings, the hedge fund’s publicly bated debt problem with “no room for er- Committee’s review of Valeant’s business
traded security arm, revealed that it had sold ror.” The gastrointestinal drug Xifaxan (rifaxi- practices unveiled a set of correspondence
off its entire interest in Valeant – more than min) faces near-term generic competition, between Ackman and the company in
27m shares and options – incurring a loss es- as does Jublia (efinaconazole), a topical which he urged the company to tell the full
timated at between $3bn and $4bn. Inves- product for onychomycosis. Valeant earn- truth about its business relationship with the
tors reacted predictably by further punishing ings will continue to contract, the analyst specialty pharmacy Philidor, adding that in-
Valeant’s stock, which dropped an additional wrote, “due to the firm’s efforts to invest in vestors increasingly distrusted answers they
10.3% on March 14 to close at $10.86. All new product launches combined with de- were getting from Valeant management.
told, the Laval, Quebec-headquartered firm clining sales from higher customer rebates Using terms like “brink of catastrophe”
has seen its share price decline by approxi- and new generic competition on several and “death spiral,” Ackman told Valeant ex-
mately 95% since peaking at $257 in 2015. high-margin products. With ongoing per- ecs in an October 2015 emails that their
Offering its rationale for selling the formance below our expectations, we see staged conference call to try to manage
shares now at a loss rather than maintain- few favorable options on the horizon.” controversies around price increases and
ing in hopes of a business rebound, Persh- One possible move Valeant could make, the Philidor relationship had worsened
ing Square said “the investment required a Waterhouse added, is to sell off the Bausch the situation.
disproportionately large amount of time & Lomb Inc. eye care unit, whose legacy Still, Ackman testified alongside Pearson
and resources. As a result, we elected to sell products continue to perform well. Theo- before the Aging Committee in April 2016,
our investment and realize a large tax loss, retically, selling this business could bring to address reports that 30 of Valeant’s top-
which will enable us to dedicate more time Valeant a solid price, he said. selling drugs had increased in price by an
to our other portfolio companies and new BMO Capital Markets’ analyst Gary Nach- average of 78%. At the time, Ackman said
investment opportunities.” man reads the Pershing Square decision to Pershing had been mistaken in taken a pas-
mean that it determined turning Valeant sive investment role in the company, but
ATTEMPTED RECOVERY around would take longer than expected asserted that frequent price increases were
Analyst Michael Waterhouse of Morningstar and face even more hurdles than initially only “a small part of the business” at the time
said Ackman’s departure at this point likely anticipated. “The timing of this decision is his company evaluated investing in Valeant.
won’t have a major effect on Valeant’s future particularly noteworthy since new man- Still, Ackman increased his initial stake from
prospects, which will be driven by getting agement is just beginning to implement a 5.6% to more than 9%, becoming second-
out of debt, realizing solid returns by selling number of its strategic initiatives, including largest holder of Valeant stock.
off assets and succeeding with the current asset sales to help pay down debt, pipeline Published online 14 March 2017
6 | Scrip intelligence | 24 March 2017 © Informa UK Ltd 2017
HEADLINE NEWS
CONTINUED FROM COVER Ibrance efficacy, however, since median Threshold/
In addition to its flexible price structure, PFS for the Pfizer drug in combination with
Novartis also believes it can compete with Molecular
letrozole was 24.8 months in the Phase III
Pfizer in terms of convenience. Hinshaw
PALOMA-2 study versus 14.5 months for le-
Templates: The
pointed out that patients can take the drug
trozole alone. Ibrance is approved for treat-
whenever they like, since – unlike Ibrance –
ment in combination with letrozole as well Power Of Two
it does not have to be taken with food.
as in combination with the selective estro-
gen receptor degrader fulvestrant for post-
Although a vehicle for Molecular Tem-
IBRANCE’S ADVANTAGE
menopausal women who fail treatment
plates to take its Engineered Toxin Bodies
Ibrance has a big and important advantage
with letrozole or other endocrine therapies.
oncology platform public, the combined
over Kisqali, of course, because it has been
Safety also is not a major differentiator for company also will seek a pathway to ap-
on the market for two years, rapidly becom-
the two drugs. Like Kisqali, Ibrance has warn- proval for Threshold’s evofosfamide for
ing a blockbuster product. Pfizer reported
ings about cardiovascular and hematologic pancreatic cancer in Japan.
$2.14bn in 2016 Ibrance sales versus $723m
adverse events in its label – pulmonary em- A reverse merger between troubled
in 2015 and Leerink analyst Seamus Fernan-
bolism and neutropenia – with neutropenia Threshold Pharmaceuticals Inc. and
dez recently forecast $3.25bn in 2017 sales,
specifically identified as a side effect that may privately held Molecular Templates
rising to $6.83bn by 2021.
require prescribers to reduce the Ibrance Inc. will take the latter company, fo-
Novartis has its own blockbuster hopes
dose. The label has separate dose-lowering cused on new a class of cancer drugs
for Kisqali – one of a dozen potential $1bn-
instructions for non-hematologic events. with potential in immuno-oncology,
plus sellers in its research and development
public. However, the combined
pipeline – but Pfizer may very well maintain
ADDITIONAL TRIALS ONGOING company remains committed to the
a strong lead in the market for CDK4/6 in-
Outside of their approved labels, Pfizer’s former’s evofosfamide, which was
hibitors. US oncologists have had two years
drug also has a lead over Novartis’s product considered dead and buried after a
to get acquainted with Ibrance, during
in the adjuvant setting where the Phase III pair of Phase III failures in late 2015.
which time it has become part of the stan-
PALLAS study began in August 2015 evalu- The two firms announced their
dard of care in first-line treatment of meta-
ating treatment with Ibrance plus an endo- merger during an investor call on
static HR+/HER- breast cancer.
crine therapy for at least five years versus March 17, outlining an all-cash
Also, with remarkably similar data for the
standard endocrine adjuvant therapy, such transaction approved by both boards
two drugs, it could be difficult for Novartis
of directors that will result in a new
as letrozole. Novartis said on March 13 that
to switch prescribers from Ibrance to Kisqali,
company called Molecular Templates
it recently began its own adjuvant study,
unless the Swiss pharma can win over both
Inc., headquartered in Austin, Texas.
which will enroll 2,000 patients.
oncologists and payers with its flexible dos-
Current Molecular Templates CEO
Ongoing Phase III trials for Kisqali in-
ing and pricing strategy.
Eric Poma, a former ImClone Systems
clude MONALEESA-3, which combines the
Kisqali plus the aromatase inhibitor/en-
Inc. executive, will become CEO of the
CDK4/6 inhibitor with fulvestrant compared
docrine therapy letrozole reduced the risk
new company, while Threshold CEO
with fulvestrant alone in postmenopausal
of death by 44% versus letrozole alone at
Barry Selick will take one of Thresh-
women with HR+/HER2- advanced breast
the first interim analysis for MONALEESA-2,
old’s two seats on the board and serve
cancer who have not been treated with or
when the Phase III trial was stopped for ef-
as chairman.
were treated only once with endocrine ther-
ficacy. The FDA relied on data from that in- Selick said the decision to merge with
apy. In MONALEESA-7, Kisqali plus endo-
terim analysis in its approval decision. Molecular Templates was reached after
MONALEESA-2 results included in the crine therapy and goserelin are being com- a lengthy process of reviewing pos-
drug’s label show that median progression- pared to endocrine therapy and goserelin sible strategic directions for Thresh-
free survival (PFS) hadn’t been reached in the alone in premenopausal women with HR+/ old, which considered more than 100
Kisqali/letrozole arm as of the first interim HER2- advanced breast cancer who have alternatives.
review, but the median PFS in the letrozole- received no prior endocrine therapy. Data Following the merger, expected to
only arm was 14.7 months (p<0.0001). PFS from both studies are expected around the close during the second quarter, exist-
ranged from 13 to 16.5 months in the com- end of 2017 or early 2018 and could support ing Molecular Templates’ sharehold-
parator arm of the study versus a minimum a supplemental filing with the FDA in 2018. ers will own nearly 66% of the new
PFS of 19.3 months in the Kisqali group. Lilly hopes that even with its third-to- company, with Threshold investors
Novartis reported that median PFS market position, its CDK4/6 inhibitor abe- owning 34%.
reached 25.3 months in the combination maciclib will be able to grab market share
[email protected], 17 March 2017
arm and 16 months in the letrozole-only from its predecessors based on potentially
arm after an additional 11 months of data improved safety. The company thinks that
Read about the next-
were collected. Overall survival data are not its more selective drug could allow for con-
generation potential in
mature, so the company expects to report tinuous dosing without the need to inter-
immunotherapy here:
those results at a later date. The data to date rupt therapy due to severe neutropenia.
http://bit.ly/2nidOsT
do not show a substantial difference from Published online 14 March 2017
scrip.pharmamedtechbi.com 24 March 2017 | Scrip intelligence | 7
EXPERT VIEW
Competition Coming For Hemophilia Franchises,
But Will Patients And Payers Embrace New Drugs?
MANDY JACKSON [email protected]
Roche’s emicizumab, Alnylam’s fitusiran A once-weekly injection of emicizum-
Top Hemophilia Franchises By
and multiple gene therapies may soon ab was an effective prophylactic therapy
2016 Sales*
steal market share from established clot- for hemophilia A patients enrolled in HA-
Shire (Baxalta): $3.7bn
ting factors sold by Shire, Novo Nordisk VEN 1, including individuals with inhibi-
Novo Nordisk: $1.5bn
and others, but safety is a key consider- tors to Factor VIII. Roche also is testing the
Pfizer: $1.3bn
ation for physicians and patients. therapy dosed every other week and ev-
Bayer: $1.2bn
ery four weeks.
Hemophilia patients are loyal to CSL Behring: $1bn “Patients on standard of care bypass
Bioverativ: $847m
brand-name clotting factors that therapy are still bleeding quite a bit; there’s
*Grifols and Octapharma do not report prod-
have enjoyed market dominance for definitely an unmet need,” Roche subsid-
uct-level sales or hemophilia franchise totals,
many years, but a shakeup may be coming iary Genentech Inc.’s Gallia Levy, associate
but they are major players in the market.
in the form of monoclonal antibodies, RNA- group medical director, told Scrip during
based treatments and gene therapies if the ASH meeting.
safety factors and treatment durability don’t back with [Biogen spinout Bioverativ Inc.’s Levy noted that many hemophilia A
get in the way. recombinant Factor IX product] Alprolix.” patients aren’t adhering to treatment
Shire PLC has the world’s largest he- Walsh was more optimistic about new regimens, because of the burden of infu-
mophilia franchise following its acquisi- biologic approaches, since subcutaneous sions three and four times per week, so
tion of Baxalta Inc., generating more than administration every one or two weeks emicizumab’s once-weekly – or even less
twice the sales of its nearest competitor would be a big convenience and compli- frequent – injections could be a significant
Novo Nordisk AS. Those companies’ mar- ance benefit compared with weekly or differentiating factor in the market.
ket dominance will be challenged, how- more frequent clotting factor infusions. However, a recently reported patient
ever, by novel therapies from the likes The doctor was less enthusiastic about death in HAVEN 1 raised new questions
of Roche, Alnylam Pharmaceuticals Inc. gene therapies, however, based on the about which patients are the best candi-
and Spark Therapeutics Inc., which could early-stage data presented to date. dates for treatment with emicizumab and
eliminate the need for frequent clotting Shire’s group vice president and head of how they should be treated when they ex-
factor infusions. US hematology Jeffrey Schaffnit said in an perience a breakthrough bleeding event.
However, hemophilia patients tend to interview with Scrip during the American Shire contends that emicizumab may
be reluctant to give up therapies that have Society of Hematology (ASH) Annual Meet- not be safe enough for patients that re-
been safe and effective for many years, ing in December that the safety of new quire frequent and life-long therapy. The
which could mean slow acceptance and therapies is key for hemophilia patients, company generated in vitro data last year
growth for newer products. who’ve relied on products like Shire’s anti- for Feiba dosed concomitantly with an
Physicians and patients are interested in inhibitor activated prothrombin coagulant emicizumab biosimilar, which showed that
new therapeutic approaches, but they are complex Feiba for decades. thrombin levels jumped four to 10 times
reluctant to switch from approved clotting “We fully support the innovation of these above pre-treatment levels, increasing the
factors, according to a Feb. 28 report from products, but they shouldn’t have any ad- risk for serious adverse events. The preclini-
Bernstein analysts Ronny Gal and Tim An- ditive risks,” Schaffnit said. “We think further cal findings were published in the journal
derson based on an interview with hemo- study is warranted.” Blood just before the ASH meeting.
philia key opinion leader (KOL) Christopher A Suntrust Robinson Humphrey analysis
Walsh, a Mt. Sinai Hospital hematologist EMICIZUMAB QUESTIONS of the in vitro data on Dec. 2 noted that
and an associate professor at the Icahn The most advanced of the new treatment thromboembolic events and thrombotic
School of Medicine at Mt. Sinai. modalities is Roche’s monoclonal antibody microangiopathy (TMA) – the serious ad-
“Within the [Factor VIII (FVIII)] market, Dr. emicizumab (ACE910), which was given verse events reported in HAVEN 1 – appear
Walsh sees little traction from the longer- prophylactically in the Phase III HAVEN to be a result of co-administration of emi-
acting FVIII products and sees many of his 1trial to patients with hemophilia A, in- cizumab with a bypassing agent, because
patients switching back to the older prod- cluding individuals who have developed the severe side effects are not known to
ucts as they do not feel ‘protected.’ Discus- antibodies – also known as inhibitors – to occur among hemophilia patients treated
sions with peers suggest at least some clotting factors. The bispecific monoclonal with Feiba or Novo Nordisk’s NovoSeven
other physicians have noted the same,” antibody mimics the production of clot- and they occurred only in patients who
the Bernstein report says. “Within the FIX ting Factor VIII to bring together Factors IXa had a breakthrough bleeding event in the
market, Dr. Walsh is seeing similar switch and X to help the blood coagulate. Roche study.
8 | Scrip intelligence | 24 March 2017 © Informa UK Ltd 2017
EXPERT VIEW
Bernstein noted in its KOL report that Mt. NovoSeven has been on the market since are looking at health care utilization costs
Sinai’s Walsh expects broad adoption of 1996 and, like FEIBA, treats patients with as will the forthcoming Phase III program,
emicizumab for hemophilia patients with inhibitors. Novo also has long-acting clot- since infusion costs are a big expense for
inhibitors if the final data expected later ting factors in late-stage development and payers in terms of reimbursing current he-
this year show an 80% or greater reduction under regulatory review as well as a Phase mophilia therapies.
in bleeding events versus 50% to 60% re- I monoclonal antibody called concizumab. “The inhibitor population has a high un-
ductions for existing clotting factors. If so, However, the company is looking for ways met need and some require treatment that
physicians are likely to use the monoclonal to diversify its revenue beyond diabetes cost $1m-plus per year,” he noted. “It’s very
antibody in the inhibitor population even and hemophilia and may expand in hema- expensive, so if you can obviate the need
without a deeper understanding of the tology, since it is rumored to be considering for bypassing agents – which have a high
safety risks. an acquisition of the sickle cell drug devel- burden, cost and risk – you can benefit pa-
But for broader used in hemophilia A and oper Global Blood Therapeutics Inc. tients and society.”
B, the risks associated with the combination Garg also pointed out the potential qual-
of emicizumab and Feiba – and potentially FITUSIRAN NEARING PHASE III ity of life improvement for hemophilia pa-
with NovoSeven – would have to be bet- Another closely-watched novel hemo- tients, many of whom avoid sports or other
ter understood, the Bernstein report notes. philia treatment in clinical development activities and plan their lives around when
That suggests that it could take a while for is the RNA interference (RNAi) therapeutic they are due to get their next clotting fac-
emicizumab to have an impact on Shire’s fitusiran from Alnylam and partner Sanofi/ tor infusion.
portfolio beyond Feiba if the product is ap- Genzyme Corp. The companies are co- “Factor doesn’t have a consistent effect
proved in the US in the next year or so. developing and will co-commercialize the over time,” he said. “We have a clear and
drug in the US, Canada and Western Europe, consistent effect; it’s freeing for patients.
while Sanofi has rights to fitusiran in the rest Seeing the bleeding rates we’re seeing is
of the world. really quite positive and encouraging.”
The drug is designed to reduce anti- Both fitusiran and emicizumab are com-
thrombin (AT), thereby increasing throm- pelling for payers, which are looking for cost
bin, which should improve clotting in savings from new subcutaneous therapies,
people with all types of hemophilia, in- which could prevent bleeds without fre-
Ontakrai cluding patients with inhibitors, and other quent and costly infusions of clotting fac-
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Alnylam presented interim Phase I data Gene therapies are not as compelling
Shire certainly has a lot at stake with for fitusiran at ASH that showed reduced in the eyes of payers, however, because
around a 50% share of the hemophilia levels of AT, increased thrombin and a me- they have not yet determined how to pay
market after closing its acquisition of Bax- dian annualized bleeding rate (ABR) of zero for what could be once-in-a-lifetime treat-
alta last year, making hemophilia the com- in 16 patients with hemophilia A or B with ments, according to a recent report from
pany’s largest franchise. Baxalta’s hematol- inhibitors who were treated with a once- Datamonitor Healthcare.
ogy franchise generated $3.7bn in 2016 monthly subcutaneous injection of fitu-
sales, which was 3% more than in 2015 on siran versus a pre-study median ABR of 31. GENE THERAPY CLAMOR
a non-GAAP basis, but Shire recognized The median ABR in the company’s Phase II Six gene therapies and a gene-editing treat-
only $2.2bn in post-acquisition hemophilia extension study was 1 as of the data cutoff ment for hemophilia are in Phase I/II test-
sales, or 20.6% of the company’s $10.7bn in for the ASH presentations. ing, although BioMarin Pharmaceutical Inc.
product sales last year. All side effects in the Phase I study were plans to move its BMN 270 for hemophilia
Novo Nordisk reported DKK10.5bn characterized as mild or moderate with A into a potentially registrational Phase IIb
($1.5bn) in hemophilia sales for 2016, no thromboembolic events reported, in- clinical trial in the third quarter of 2017, and
which accounted for 9.4% of the Danish cluding among patients who experienced uniQure NV intends to begin a pivotal trial
company’s DKK111.8bn ($15.9bn) in prod- breakthrough bleeds that were managed for its hemophilia B candidate AMT-060 later
uct sales. Novo said in its annual report that with bypassing agents – recombinant Fac- this year as well.
its hemophilia sales declined by 2% from tor VIIa and/or activated prothrombin com- Spark and Dimension Therapeutics Inc.
2015 levels, because of “lower NovoSeven plex concentrate (Shire’s Feiba and Novo continue to report data from ongoing
sales in the USA due to increased compe- Nordisk’s NovoSeven). Phase I/II clinical trials for their hemophilia
tition and patients participating in clinical “Patients are very excited about some- gene therapies, but Sangamo BioSciences
trials with competing drugs, partly offset thing with such a different approach,” Al- Inc. only recently started trials for its hemo-
by the roll-out of NovoEight in Europe and nylam chief medical officer Pushkal Garg philia A gene therapy SB-525 and its hemo-
the USA, and by sales growth for NovoS- said in an interview with Scrip during ASH. philia B gene-editing therapy SB-FIX and
even in [Asia] Pacific.” Garg said the ongoing early-stage studies CONTINUED ON PAGE 10
scrip.pharmamedtechbi.com 24 March 2017 | Scrip intelligence | 9
EXPERT VIEW
CONTINUED FROM PAGE 9 tific Symposium Apr. 6 to 8 in Scottsdale, little value in AMT-060 given 1) competi-
expects its first data from those studies in Arizona. Discussions with the FDA are on- tion, 2) small market size and 3) adequacy
late 2017 or early 2018. Spark and uniQure going about the design of a Phase III study, of existing therapeutics. Given the com-
reported interim results during the ASH which would be run by Pfizer. petition from SPK-9001 and availability of
conference in December. Spark and its Spark’s wholly-owned hemophilia A long-acting recombinant FIX replacement
partner Pfizer Inc. presented data from gene therapy SPK-8011, which delivers therapeutics (yielding about 20% FIX ex-
seven out of nine adult patients with he- Factor VIII, is about a year behind SPK- pression with weekly prophylactic dosing),
mophilia B who were at least 12 weeks past 9001, so the first set of data from an on- we see little commercial opportunity for
infusion with the gene therapy SPK-9001 as going Phase I/II study are expected in AMT-060.”
of the Nov. 30 data cutoff. Those individuals mid-2017. Even so, Yang said uniQure has about
were able to produce Factor IX (FIX) at suf- “We continue to see a reasonable a 75% chance of winning FDA approval
ficient levels after a single infusion. chance to show clinically meaningful im- for AMT-060 based on available data.
Baseline FIX levels were less than 2% of provement in [the] initial cohort … based She forecast cumulative sales of $785m
normal, but increased to a range of 12% to on preclinical data,” Leerink analyst Gena between 2020 and 2032 – an average
46% of normal with a mean steady-state Wang said in regard to SPK-8011 in a Feb. of $60.4m per year – based on the gene
level of 28%; that’s more than twice the 22 report on Spark’s pipeline. therapy’s potential to penetrate a market
12% level deemed sufficient to prevent of about 7,000 hemophilia B patients in
minor, chronic bleeding in the joints – a UNIQURE GENE THERAPY the US and EU.
common cause of disability in hemophilia. UniQure will report additional data from “Dr. Walsh believes gene therapy works
“Most people are not going to bleed at its Phase I/II study for AMT-060 for hemo- in principle, but its adoption is gated by
that level,” Spark co-founder, president and philia B in 2017 as it prepares to initiate high variability of results,” the Bernstein
chief scientific officer Katherine High said a pivotal study this year, but at the ASH KOL report said. “He expects gradual
in an interview at ASH. meeting the company presented results adoption as the technology gets better,
Six patients reported increased physical from ongoing earlier-stage study for pa- but this would require multiple genera-
activity and improved quality of life, be- tients in the low-dose cohort treated for tions of products (it would not be first-
cause they did not have to continue with up to 52 weeks and in the higher-dose to-market wins).”
once- or twice-weekly clotting factor infu- cohort for up to 31 weeks. Three patients That may be good news for Shire after
sions. Patients have indicated that the ben- across both cohorts were given tapering all, since the company has gene therapies
efit for gene therapy is “the freedom from doses of corticosteroids to treat mild in- in preclinical development for hemophilia
worrying about when you’re going to bleed creases in liver enzymes. A and B – SHP654 for hemophilia A and
and when was your last infusion,” High said. Four out of five patients in the second SHP648 in hemophilia B, which were ac-
“The goal of all drug development is to cohort required chronic FIX infusions prior quired by Baxter International Inc. before
give patients choice in how they manage to the clinical trial (the fifth had less se- it spun out Baxalta as a separate company.
their disease,” she added. “Patients find this vere disease and used FIX therapy only as Both assets were initially developed by
life-changing.” on-demand treatment) and were able to Chatham Therapeutics LLC.
However, Spark reported that two pa- discontinue prophylactic FIX therapy after “The biggest thing to overcome [in gene
therapy] is the immune response … but
tients had elevated liver enzymes associ- receiving AMT-060. Only one spontaneous
there’s a lot of technology looking at what
ated with an immune response to the viral bleed was reported at the data cutoff after
can be done to minimize that, looking at
vector capsid that’s used to deliver FIX DNA the hemophilia B patients stopped pro-
new capsids and vectors. It’s as close as it’s
to the liver. They were treated with taper- phylactic FIX therapy.
ever been in terms of commercialization,”
ing courses of corticosteroids and their All five patients in the first cohort had
Schaffnit said.
FIX levels dropped, but the two patients uncontrolled bleeding episodes despite
“We want to maintain our leadership;
did not have any breakthrough bleeding prophylactic FIX therapy prior to treatment
we’re looking to expand our breadth,” he
events or require FIX infusions. with AMT-060. They maintained “robust,
added, noting Shire’s investments in gene
High said the immune response seems constant and clinically meaningful levels
therapies, treatments for ultra-rare disor-
to occur between four and eight weeks of FIX activity” for up to 52 weeks, accord-
ders, like Von Willebrand disease, and the
after infusion with SPK-9001, so Spark will ing to uniQure, with a mean FIX expression
company’s Phase I long-acting recombi-
look for signs of an immune response dur- level of 5.2%.
nant Factor VIII candidate SHP656, which
ing that period going forward and treat it None of the 10 hemophilia B patients
is being developed with technology from
with steroids before FIX levels fall too far. across both cohorts of the study devel-
Xenetic Biosciences Inc.
No patients treated with SPK-9001 devel- oped inhibitors. The safety and efficacy
Published online 15 March 2017
oped FIX inhibitors and none experienced data supported uniQure’s decision to
thrombotic events or other series side ef- test the higher dose in its forthcoming
CLICK
fects. More data from the 10-patient Phase pivotal trial.
View Hemophilia
I/II study and an update on Phase III plans Jefferies analyst Eun Yang said in a report
Pipeline here:
are expected around the Hemostasis and issued on Dec. 5 in response to the data
http://bit.ly/2mkRGix
Thrombosis Research Society (HTRS) Scien- presented at ASH that “we continue to see
10 | Scrip intelligence | 24 March 2017 © Informa UK Ltd 2017