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Biotech/Pharma Prezi

Companies, landscape, deals, news, r&d, pipelines, and presentation on LysosomalStorageDisease
by

Casey McDonald

on 25 March 2016

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Transcript of Biotech/Pharma Prezi

Orphan Drugs Classificaions
Competitive Intelligence
pubs

EV/sales-->Definition of 'Enterprise-Value-To-Sales - EV/Sales'
A valuation measure that compares the enterprise value of a company to the company's sales. EV/sales gives investors an idea of how much it costs to buy the company's sales. This measure is an expansion of the price-to-sales valuation, which uses market capitalization instead of enterprise value. EV/sales is seen as more accurate because market capitalization does not take into account as well as enterprise value the amount of debt a company has, which needs to be paid back at some point. Generally the lower the EV/sales the more attractive or undervalued the company is believed to be.
Terminology
CAGR-compound annual growth rate
Some other topics, drugs and indications
obesity
sequencing
personalize medicine
big story in march/april2012
-FDA requiring weight loss meds to have additional cardio data
meds in trials this might affect
- set to decide in mid-April on Vivus Inc's Qnexa
-Arena Pharmaceuticals Inc's lorcaserin in May
-Contrave by Orexigen Therapeutics Inc has several more years of trials ahead

-phen phen pulled in 97 because of heart valve complications
-The last obesity drug to be approved by the FDA was Xenical, made by Roche Holding AG, and approved in 1999.
-In 2010, Abbott Laboratories pulled its weight-loss drug Meridia from the U.S. after a study revealed it increased heart attack and stroke risks in some patients
Risk Evaluation and Mitigation Strategies

Prior to REMS, they had the less severe Risk MAP, Minimization Action Plan

Changed to REMS in 2007/2008

There are currently approved and released REMS

There is also a section for opioids
REMS
FDA stuff
Market-->WIKI
Short float rate--short interest ratio, SIR
--is a metric signaling prevailing investors' sentiment. The ratio is calculated by dividing the number of shares sold short by the average daily trading volume, generally over the last 30 trading days. The ratio represents the number of days it takes short sellers on average to repurchase all the borrowed shares. The ratio is used by both fundamental and technical traders to identify trends

-short squeeze can occur if the price of stock with a high short interest begins to have increased demand and a strong upward trend. To cut losses, short sellers may add to demand by buying shares to cover short positions, causing the share price to further escalate temporarily. Short squeezes are more likely to occur in stocks with small market capitalization and a small public float

In finance, short selling (also known as shorting or going short) is the practice of selling assets, usually securities, that have been borrowed from a third party (usually a broker) with the intention of buying identical assets back at a later date to return to that third party. The basic principle followed is that selling something high now, to buy lower later, is profitable. The short seller (speculator) hopes to profit from a decline in the price of the assets between the sale and the repurchase, as the seller will pay less to buy the assets than it received on selling them. The short seller will incur a loss if the price of the assets rises (as it will have to buy them at a higher price than it sold them), and the loss that can be incurred by a short seller is only limited by the total strike price. Other costs of shorting may include a fee for borrowing the assets and payment of any dividends paid on the borrowed assets. "Shorting" and "going short" also refer to entering into any derivative or other contract under which the investor similarly profits from a fall in the value of an asset. Mathematically, short selling is equivalent to buying a negative amount of the assets.

Short selling is almost always conducted with assets traded in public securities, commodities or currency markets, as on such markets the amount being made or lost can be monitored in real time and it is generally possible to buy back the borrowed assets whenever required. Because such assets are fungible, any assets of the same type bought on those markets can be used to return to the lender.

Going short can be contrasted with the more conventional practice of "going long", whereby an investor profits from any increase in the price of the asset

Cholesterol
PCSK9s
Amgen’s evolocuma
Sanofi’s and Regeneron’s
alirocumab
Esperion’s ETC-1002
saw them at Newsmakers -Sept 2014- interferes with cholesterol synthesis and carbohydrate metabolism by inhibiting ATP-citrate lyase
read wsj larry huston from 10/2/14
also -these two compounds, Merck's ezetimibe, pure LDL lowering, LDL as a suurogate endpoint, IMPROVE-IT trial with actual long term data

Orphans
Lipid Storage
Obesity
Metabolic/Cardio
Hep C
Infectious
Risk Evaluation and Mitigation Strategies

Prior to REMS, they had the less severe Risk MAP, Minimization Action Plan

Changed to REMS in 2007/2008

There are currently approved and released REMS

There is also a section for opioids
REMS
EMA stuff
Market
AD
CNS
PD
Rheum
Inflam/Autoimmune
Pain
Pain
AMD
Ophthalm
Glaucoma
PMO
Osteo
Psoriasis
Derm
Lupus (SLE)
Deals
M&A
Sales, Marketing
Solid
Cancer
Blood
solvadi (sofosbuvir)
by Gilead from Pharmasset
-defective substrate of NS55B the viral rna polymerase, inhibits rna synth
-approved dec 2013
-12 weeks for $84k - for genotypes 1 and 2
- for genotype 3 24 weeks at $168k
-tiered pricing which means how much in other countries?
branded
lucentis roche aanndd novartis?
eylea regn and bayer?
off label avastin >60% use in US
5 tnfs
in order?
enbrel
humira
remicade
simponi
cimzia
add generic term and companies
BMS's asunaprevir - a NS3/4A protease
was going for subtype 1b as a combo with Daklinza (daclatasavir) a NS5A inhibitor
- had maybe eyed japan with big 1b population? but calling it quits? oct 2014
daclatiasavir - CRL in Dec 2014 - demanding more data for combination use

"nuc"
solvadi will get approval (oct 2014 its certain) for combo with ledipasvir (their NS5B inhibitor)
--in same subpop?
bms still has combo of 3 --daclatasavir, asunaprevir and BMS-791325
-this cocktail is for tough pts, pre and post liver txplant, co-HIV infected
abbvie's and merck's?
CROs
Other Pubs
Pharmavoice
fierce
bpi
Pharmaceutical commerce

Immunotherapies
PD-1 and PD-L1
Bristol-Myer’s Squibb’s CTLA-4 inhibitor Yervoy (ipilimumab)
Merck’s PD-1 blocker Keytruda (pembrolizumab)
Bristol’s PD-1 inhibitor Opdivo (nivolumab)
Genentech/Roche’s PD-L1offering, MPDL3280A (RG-7446) --- this is now atezolizumab - strong lung cancer results -
MedImmune/AstraZeneca PD-L1 MEDI-4736
-chimeric antigen receptor (CAR-T) therapies could make a big impact. Unlike PD-1/PD-L1 inhibitors, which unchain immunity, CAR-Ts activate the immune system, which offers intriguing possibilities, as well as possible dangers.
Novartis is first in the CAR-T line with CTL019
Amgen’s blinatumomab, a bi-specific T-cell engager (BiTE)
Targeted therapies
Pipeline drugs
PARP inhibitors
which encourage cancer cell death by limiting this DNA-repair enzyme
veliparib from Abbvie
rucaparib from Clovis Oncology/Pfizer
Lynparza (olaparib) from AstraZeneca
BMN-673 from BioMarin
CDK4/CDK6 inhibitors
great potential for adjuvant treatment
Lilly’s abemaciclib
Onyx/Pfizer’s palbociclib
Heart Failure
Novartis’s heart failure and hypertension treatment LCZ696. The drug has novel mechanisms, combining sacubitril to preserve peptides that lower blood pressure and valsartan to improve vasodilation -->could supplant ACE inhibitors and ARBs
Novartis’ other heart failure drug has hit hard times. In May this year, the FDA rejected Novartis’ biologics license application for Serelaxin. A synthetic human relaxin 2 hormone
NLG919, an IDO pathway inhibitor - Genentech partnered with NewLink
DMD - Duchenne's muscular dystrophy
Sarepta (SRPT) - eteplirsen
Prosensa (RNA) - Drisapersen
PTC - Ataluren
late Oct 2014 - Sarepta keeps adding delays, confidence is waning
Myelofibrosis
Hematology
Incyte's Jakafi (ruxolitinib)
Diabetes
Endocrine
GLP-1s
basal insulins--which are long-acting products often supplemented with fast-acting insulins at meals
--> Sanofi is hoping to launch its Lantus follow-up Toujeo in the U.S. next year. Novo has its own follow-up, Tresiba, which is delayed till 2016, thanks to the FDA's demand for more safety data. And Lilly and its partner Boehringer have tentative FDA approval in hand for their Lantus biosimilar, though they can't launch till a patent fight with Sanofi resolves
Sanofi's Lantus (insulin glargine) --more than $7 billion in 2013 sales
head to head with
Novo Nordisk's Levemir (insulin detemir)
pricing battles

Novo's "modern insulin" NovoLog
by Novo - GLP-1 drug Victoza
lilly's humalog (insulin lispro)
lilly's Trulicity, a weekly glucagon-like peptide-1 (GLP-1) receptor agonist, is indicated for adults with type 2 diabetes
vs
more on CAR-T --CTL019 is a new therapy that is made by extracting T cells from patients and arming them with chimeric antigen receptors, which essentially trains the immune system's foot soldiers to track down and kill tumor cells
Adoptive cell transfer is like “giving patients a living drug,” continued Dr. Brentjens.

That’s because ACT’s building blocks are T cells, a type of immune cell collected from the patient’s own blood. After collection, the T cells are genetically engineered to produce special receptors on their surface called chimeric antigen receptors (CARs). CARs are proteins that allow the T cells to recognize a specific protein (antigen) on tumor cells. These engineered CAR T cells are then grown in the laboratory until they number in the billions. (See the box below.)

The expanded population of CAR T cells is then infused into the patient. After the infusion, if all goes as planned, the T cells multiply in the patient’s body and, with guidance from their engineered receptor, recognize and kill cancer cells that harbor the antigen on their surfaces.
Juno in Seattle and other players like Kite ($KITE) and bluebird ($BLUE) have been ramping up their own efforts. But CAR-T treatments aren't without risk. Eight of the children in this study experienced a cytokine storm that was so severe they had to be hospitalized. But they all recovered.

"Everybody gets some kind of CRS" reaction, says Grupp, and a third of them end up in the ICU with serious reactions. But investigators have also learned that by blocking IL-6 with the immunosuppressant tocilizumab, they can often prevent the worst reactions
CAR-T
BACE inhibitors...
Merck ($MRK), meanwhile, has emerged as the leader in the BACE race, accelerating a late-stage study of its own BACE drug--MK-8931--after clearing a safety hurdle in the clinic. Biogen Idec ($BIIB) recently partnered with Eisai on E2609
...Boehringer Ingelheim and its biotech partner Vitae Pharmaceuticals ($VTAE) have survived the first challenge in the crowded race to develop a BACE inhibitor for Alzheimer's disease. The newly public Vitae reported after the market closed on Thursday that the oral BI1181181/VTP-37948...Off-target toxicity was the likely culprit behind the death of Eli Lilly's ($LLY) BACE program for LY2886721...That failure, one in a series of setbacks for the pharma giant in Alzheimer's, pushed Lilly to ink a $500 million deal--$50 million upfront--with AstraZeneca to take charge of its BACE drug--AZD3293. Roche ($RHHBY) also killed off an early-stage effort, though it has yet to attempt to explain why. Astellas recently backed out of its $760 million deal with CoMentis on another early-stage BACE drug.
BACE inhibitors
Prana
PCSK9s --antibody that blocks the protein PCSK9, thereby helping the body clear LDL cholesterol from the blood --This protein plays a major regulatory role in cholesterol homeostasis. PCSK9 binds to the epidermal growth factor-like repeat A (EGF-A) domain of the low-density lipoprotein receptor (LDLR), inducing LDLR degradation. Reduced LDLR levels result in decreased metabolism of LDL-C, which could lead to hypercholesterolemia.....LDL-C is removed from the blood when it binds to an LDLR on the surface of liver cells, and is taken inside the cells. When PCSK9 binds to an LDLR, the receptor is destroyed along with the LDL particle. But if PCSK9 does not bind, the receptor can return to the surface of the cell and remove more cholesterol...Other variants are associated with a rare autosomal dominant familial hypercholesterolemia (HCHOLA3). The mutations increase its protease activity, reducing LDLR levels and preventing the uptake of cholesterol into the cell
also - PFE's bococizumab
race to be firist PCSK9---Amgen is suein...amgen had been in the lead....But Sanofi and Regeneron made things interesting over the summer when they paid $67.5 million for an FDA voucher that will cut alirocumab's review time down from 10 months to 6 months. The two plan to submit their treatment by year's end, which would put both drugs up for approval next June.
Asthma
Lung
IL5 agent- injectable mepolizumab--blocking he IL5 preventing buildups of WBCs in the lungs that can exacerbate asthma. GSK is angling to get the drug approved as a treatment for sufferers of severe asthma who aren't getting the relief they need from inhaled therapies
Pulmonary hypertension
Pulmonary fibrosis
Pharmacovigilance
EVMPD -in Europe - extended eudravigilance medicinal product dictionary
- EudraVigilance launched in 2001 and
-EVMPD launched in 05
-data processing management system for reporting and evaluating suspected adverse drug reactions (ADRs) during the development and post marketing authorisation approval

Is this the biggest AD trial?
After teaming up in September to develop its experimental Alzheimer's drug, AstraZeneca (NYSE:AZN) and partner Eli Lilly (NYSE:LLY) have begun a large trial for the product, known as AZD3293 or LY3314814.The pivotal Phase II/III clinical trial will involve more than 1,500 patients with early Alzheimer's and is expected to be completed in 2019...announced Dec 1 2014
-->this is their BACE inhibitor
BACE inhibitors
MS
Gilenya -
Novartis' (NYSE:NVS) Gilenya (fingolimod), approved for relapsing multiple sclerosis (MS) in the U.S. and highly active relapsing-remitting MS in Europe, failed to demonstrate a significant difference compared to placebo on a combination of disability measures in a Phase 3 trial evaluating the drug in primary progressive multiple sclerosis (PPMS)
BioMarin bought Prosensa for as much as $840m? - late Nov2014
Device
Medtronic ($MDT) scored EU regulatory approval for its $43 billion acquisition of Covidien ($COV), days after U.S. antitrust authorities signed off on the deal subject to certain conditions.

The Minneapolis, MN-based company on Friday got a green light from the European Commission for its pending merger as long as the companies sell Stellarex, a drug-coated balloon being developed by Covidien, The Wall Street Journal reports. Last week, Medtronic agreed to sell the Irish devicemaker's drug-coated catheter business to Spectranetics ($SPNC) to settle Federal Trade Commission (FTC) charges that its acquisition of Covidien was anticompetitive
Medtronic buying Covidien - late 2014 - pending sale of drug coated catheter
Biogen's , Tecfidera (BG-12) new standard of care in MS
Biogen Idec's BIIB037 - antibody targeting beta amyloid proteins - signal in a safety, Ib study - Biogen noted a dose- and time-dependent reduction in amyloid levels at 52 weeks - they'll aggressively try for ph3 - fair amount of hype on this with a dec 2014 announcement
so many failures --including Eli Lilly's ($LLY) solanezumab and Pfizer ($PFE) and Johnson & Johnson's ($JNJ) bapineuzumab-- great potential in early trials only to fail miserably in Phase III, contributing to a daunting 99.6% clinical trial failure rate for such drugs, according to Cleveland Clinic's Jeffrey Cummings. - from fierce
JAKs
PFE Tofa
Galapagos' JAK 1 specific...with Abbvie
other Jaks -
Incyte and Lilly's baricitinib
Vertex VX-509
Astellas' ASP015K --which JnJ abandoned?- Astellas to go it alone for Phase 3?
Financial terms
PEG ratio - DEFINITION OF 'PRICE/EARNINGS TO GROWTH - PEG RATIO'
A stock's price-to-earnings ratio divided by the growth rate of its earnings for a specified time period. The price/earnings to growth (PEG) ratio is used to determine a stock's value while taking the company's earnings growth into account, and is considered to provide a more complete picture than the P/E ratio. While a high P/E ratio may make a stock look like a good buy, factoring in the company's growth rate to get the stock's PEG ratio can tell a different story. The lower the PEG ratio, the more the stock may be undervalued given its earnings performance. The calculation is as follows:

P/E ratio ÷ Annual EPS Growth

INVESTOPEDIA EXPLAINS 'PRICE/EARNINGS TO GROWTH - PEG RATIO'
The PEG ratio that indicates an over or underpriced stock varies by industry and by company type, though a broad rule of thumb is that a PEG ratio below one is desirable. Also, the accuracy of the PEG ratio depends on the inputs used. Using historical growth rates, for example, may provide an inaccurate PEG ratio if future growth rates are expected to deviate from historical growth rates. To distinguish between calculation methods using future growth and historical growth, the terms "forward PEG" and "trailing PEG" are sometimes used.
the copmanies in CAR-T
-JNJ struck a deal with Transposagen in Lexington, KY!
but the main players....from fierce
Novartis ($NVS), Kite Pharma ($KITE) and Juno Therapeutics--which just won breakthrough drug status at the FDA--each have their own anti-CD19 CAR T programs in development. Celgene ($CELG), in collaboration with bluebird bio ($BLUE), poses a competitive threat using technology from Baylor College of Medicine, while GlaxoSmithKline ($GSK) has entered into a $350 million T-cell reengineering deal with Adaptimmune in the U.K.
Vaccines
in vaccines for 2015, especially in the tropical endemic disease arena. Sanofi’s live, attenuated, tetravalent dengue vaccine (CYD-TDV) is likely to launch in 2015 as is GSK’s RTS,S the world's first vaccine against malaria, said Fitzpatrick.
topics for 2015:
1) One year ago, Express Scripts (ESI) moved to block 47 products from their national formulary.
--> The question for 2015 will be, what other commercial plans will emulate ESI by moving to more restrictive formularies
2) How will the Office of Inspector General (OIG) of the HHS come down on drug manufacturers who may have run afoul of anti-kickback laws allowing federally subsidized patients to use copay coupon cards? Subsidized patients, like patients on Medicare part D, should not be permitted to use copay cards, but they figure out ways to do it,--- There’s a chance that the fallout from OIG’s report could result in a real mess
3) The increasing exposure of patients to high deductible plans could have a major impact on branded drugs, --As more and more employers move to high deductible plans, patients will start seeing the full price of their medications after a first and second fill, he explained. With these increases, many patients could look to flip to a generic or stop taking their medications altogether.

Insurance, ACA, PBMs, etc
comingling
personal mandate
separate medical/rx deductables
Ebola vaccines?
Merck working with Newlink-VSV-EBOV
, but this might not get out of Phase 1...safety snag in Dec 2014 - although the safety issue could be minor - joints? discomfort, soreness
NIH is ready to move... early 2015 - blueprinted a Phase III trial for rVSV-EBOV to kick off in early 2015, studying NewLink's vaccine alongside one developed by
GlaxoSmithKline
($GSK)
$
JNJ'
s investment in Ebola - $200m, which includes equity investment in partner Bavarian Nordic...JNJ's efforts (from fierce) betting on technology from Janssen's Crucell arm, dubbed
AdVac
, which uses harmless adenoviruses as vectors to carry new genetic material encoding for a range of pathogens. For a combination approach, Janssen is adding a vaccine platform from Denmark's Bavarian Nordic called
MVA-BN
, which uses re-engineered viruses as vectors to express foreign genes. Together, the two work as a prime-boost vaccine, using one vector to prime and another to boost immune response.

Johnson & Johnson is also investigating previously tested drugs that may be able to help patients survive an Ebola infection.
For HPV
Merck's ($MRK) Gardasil - Dec 2014 - approval of Gardasil 9...so they keep on improving it? of course sex is an issue (stigma). They have a study showing the vaccine didn't lead to increased risky sexual behavior
Ebola vaccine developers HHS provide liability protections for the companies --immunity was declared under the Public Readiness and Emergency Preparedness (PREP) Act, and it protects drugmakers against legal claims related to the manufacturing, testing, development, distribution and administration of three Ebola vaccines, the department said in a statement. It is a protection the U.S. has used before to fast-track vaccine development.
IPOs on top of CAR-T craze?
Juno - pretty huge IPO? $191m in dec 2014?
Bellicum with $121m?
Antibiotics
Ebola vaccine developers HHS provide liability protections for the companies --immunity was declared under the Public Readiness and Emergency Preparedness (PREP) Act, and it protects drugmakers against legal claims related to the manufacturing, testing, development, distribution and administration of three Ebola vaccines, the department said in a statement. It is a protection the U.S. has used before to fast-track vaccine development.
why is developing drugs for antibiotics so tough...not lucrative
-for one, there one off cures, can't treat someone for years on an antibiotic
Merck going for Cubist....
Merck ($MRK) is shelling out $9.5 billion for antibiotics specialist Cubist Pharmaceuticals ($CBST), joining the wave of major drugmakers with a renewed interest in anti-invectives
--what other deals are in this wave?
Merck gets an established leader in antibiotics with a wide pipeline of new treatments.
Cubicin
, Cubist's anchor product, pulls in roughly $1 billion a year, and the company recently launched
Sivextro
, a superbug treatment it picked up in its $707 million deal for Trius Therapeutics last year....also from cubist-->expecting FDA approval this month (Dec 2014) for
ceftolozane/tazobactam
, a combination antibiotic designed to fight complicated urinary tract and intra-abdominal infections,
pipeline includes treatments for hospital-acquired bacterial pneumonia, Clostridium difficile and opioid-induced constipation.
history of inattention to antibiotic R&D is in part responsible for the current increase in demand--and market opportunity--for anti-invectives. Now, buoyed by government incentives, Big Pharma is creeping back into the space, with the likes of Roche ($RHHBY) and Actavis ($ACT) spending big to beef up their pipelines.
Novartis' news at ASH in Dec 2014 was pretty huge - Novartis' (NYSE:NVS) investigational chimeric antigen receptor (CAR) therapy, CTL019, demonstrates profound efficacy in a 39-patient study in children and young adults with r
elapsed/refractory acute lymphoblastic leukemia (ALL)
. Thirty-six of the 39 patients
(92%) experienced complete remissions
Sustained remissions were achieved up to one year or more
. Event-free survival at six months was 70% and overall survival (OS) was 75%, in most cases without further therapy.Lead investigator Stephan Grupp, Ph.D., M.D., says, "We're seeing pediatric patients who have not responded to any other therapy achieve complete remission as a result of treatment with CTL019. Now that these patients have been followed for a longer period of time, we're seeing that a number of them remain in remission for one year or more. This lead me to believe the persistence and durability of CAR-modified cells may help protect against relapse."CTL019 used CAR technology to reprogram a patient's own T cells to attack cancer cells that express proteins called CD19. After the cells have been reprogrammed they are re-infused into the patient where they seek out and kill tumor cells.Novartis has worldwide rights to CARs developed through its collaboration with the University of Pennsylvania. The FDA designated CTL019 a Breakthrough Therapy in July.
Biosimilars
BIO and GPha compromise....this in Biocentury in Dec 2014
Generic Pharmaceutical Association (GPhA) and the Biotechnology Industry Organization (BIO) have agreed to introduce the same proposal to state legislatures next year concerning the substitution of interchangeable biologics for branded biologics. The final compromise proposal removes language opposed by GPhA that would have required pharmacies both to notify prescribing physicians of a substitution and obtain written patient consent for a substitution prior to dispensing an interchangeable biologic. Instead, according to GPhA, physicians now must be notified after the biologic is dispensed, and patient consent would not be required.
BIO maintains that prescribing physicians must be informed if biologics are substituted in order to appropriately assess a patient’s experience and further treatment options.
The compromise will require pharmacies to inform physicians of the specific product prescribed within a "reasonable time" after dispensing either the originator or interchangeable biologic. According to BIO, the definition of a "reasonable time" would generally be left up to individual states and pharmacies.
The amended proposal also would require pharmacies and prescribing physicians to maintain electronic records of their communications regarding biologics prescriptions.
Under the Biologic Price Competition and Innovation Act (BPCIA), once FDA deems a biosimilar as interchangeable with its reference product, the follow-on biologic may be substituted without intervention from the prescribing physician.
BIO v GPhA--what are their stakes?
Depression
Neuro
H. Lundbeck A/S (CSE:LUN) and Otsuka Pharmaceutical Co. Ltd. (Tokyo, Japan) said all three doses of once-daily brexpiprazole (OPC-34712) -- for major depressive disorder- ph3
Myelofibrosis--rare hematologic cancer--the only approved orphan drug for myelofibrosis is Jakafi (ruxolitinib), and the only potential ‘curative’ treatment is allogeneic bone marrow transplant
CLL
NHL - non-Hodgkin lymphoma --CAR-T showing promise here
ALL- acute lymphoblastic leukemia - some of CAR-T showing great results here....adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia
Amgen's Blincyto (blinatumomab) to treat patients with Philadelphia chromosome-negative (Ph-) precursor B-cell acute lymphoblastic leukemia (ALL), a rare form of ALL--approval came in dec 2014- 5 months early, why so early?
--fierce--is an antibody developed through Amgen's bispecific T cell engager (BiTE) system, designed to direct the body's disease-fighting immune cells to attack cancerous growth- works by connecting CD19, a protein commonly found on cancer cells, to CD3, which is expressed by the immune system's T cells. By drawing the two proteins together-1rst approval for any CD19-targeting agent, a class that includes promising immunotherapies from Novartis ($NVS), Juno Therapeutics, Kite Pharma ($KITE) and others--Amgen has moved quickly with blinatumomab since picking it up in a $1.2 billion buyout of Micromet in 2012, and the immunotherapy is also in development as a treatment for chronic lymphocytic leukemia, B-cell lymphoma and other blood and marrow cancers.
REVLIMID (lenalidomide) in combination with dexamethasone (dex) is indicated for the treatment of patients with multiple myeloma (MM) who have received at least one prior therapy
-REVLIMID chronic lymphocytic leukemia (CLL) in controlled clinical trials only
-thalidomide analogue
pfe's famous AD failure was Pfizer paid a $225 million upfront for rights to Dimebon (Latrepirdine), a drug that failed decisively for Alzheimer's - from a russian company? - an antihistamine drug which has been used clinically in Russia since 1983
plavix (Clopidogrel) - - blood thinner/anticoagulant...for heart attacka dn stroke..etc...irreversibly inhibiting a receptor called P2Y, an adenosine diphosphate (ADP) chemoreceptor on platelet cell membranes. Adverse effects include hemorrhage, severe neutropenia, and thrombotic thrombocytopenic purpura by BMS and Sanofi, one of their patent cliff drugs in 2013 -on wiki - Before the expiry of its patent, clopidogrel was the second-most prescribed drug in the world. In 2010, it grossed over US$9 billion in global sales.
inhalable Afrezza, form Mannkind, marketing with Sanofi - approved in Jun 2014? with severe rems for lung problems - post marketing studies, etc
HD
Auspex - SD-809 - good ph3 data for HD Chorea - VMAT-2 Inhibitor for the Treatment of Hyperkinetic Movement Disorders- expect to file NDA in mid 2015
Forbes article on Forest/Actavis's Namenda - 12/18/14---Forest Pharmaceuticals, now part of Actavis , touting Namenda XR. Namenda (generic name: memantine) is an NMDA receptor antagonist that is prescribed to improve cognitive function in patients with Alzheimer’s Disease---so critical of pushing extended release version, which is a new formulation, as the drug itself is going off patent ---this is all OK. After all, you are letting the marketplace dictate the decision of what constitutes the value of a new medication.----Actavis, however, has taken an unusual position is that it is going to stop selling Namenda
Gastro
proton pump inhibitors, the incredibly effective drugs against heartburn and ulcers that were introduced in the late 1990s and are now available over-the-counter. The first of these, AstraZeneca and Merck’s Prilosec, became the best-selling drug in the world...
led to a war for access on insurer formularies, as other drugs liked Prevacid and Protonix were introduced. All became blockbusters, but Prilosec never lost its dominance. AstraZeneca transitioned it to being a big over-the-counter brand, and was able to introduce a second pill, Nexium, that remained a blockbuster despite having paltry advantages over its competitors.
-->from Matthew Herper's 12/22/14 article about drug pricing pertaining to Gilead's Solvaldi/Harvoni vs Abbvie's Viekira Pak
Abbvie's Viekira Pak - deal with express scripts - undisclosed discsount - price competition with Gilead
Jan8 2015 - Sandoz (a Novartis co) positive --is this an adcom? -FDA -Oncologic Drugs Advisory Committee (ODAC) recommended approval of its investigational biosimilar filgrastim in the US. - Committee also recommended approval of the biosimilar for use in all indications included in the reference product's (Amgen's NEUPOGEN) label. - ZARZIO in other countries...ZARXIO in US
IBRANCE palbociclib (PD 0332991), a novel oral selective inhibitor of cyclin-dependent kinase 4/6 (CDK 4/6), for the treatment of breast cancer
Misc
Eroom's Law", the opposite of Moore's Law, which seems to chart the regress in drug approvals and novel medicines contrary to Moore's bucolic vision of technological progress
-why?
-->the 'Better than The Beatles' effect.
-->the 'cautious regulator'
--> 'throw money at it' tendency.
-->'basic science-brute force' problem and it seems to point to a rather paradoxical contradiction; that the increasingly basic-science and data-driven approaches in the pharmaceutical industry over the last twenty years might have actually hampered progress.
interesting artcile on it
http://wavefunction.fieldofscience.com/2012/03/unstoppable-moore-hits-immovable-eroom.html
Me-->does this involve --No more low hanging fruit? Are the beatles the low hanging fruit?
India -shamefeul on Sovaldi -
patent office slaps Gilead in the face
Jan 14 2015, 15:25 ET | About: Gilead Sciences, Inc. (GILD) | By: Douglas W. House, SA News Editor Contact this editor with comments or a news tip
In a superb example of what is wrong with patent protection there, India's patent office rejects Gilead Sciences' (GILD +2.1%) application for Sovaldi (sofosbuvir). The application was contested by Natco Pharma and the non-profit Initiative for Medicines, Access & Knowledge on the grounds that Sovaldi was not a significant improvement over a prior compound.According to the ruling, Gilead had to prove that Sovaldi offered better efficacy that the prior compound (a slam dunk if there ever was one). In its opinion, it did not. It noted that a "molecule with minor changes, in addition to the novelty, must show significantly enhanced therapeutic efficacy" compared to an earlier drug.The ruling is a setback for Gilead since it opens the floodgates for generic competitors. Gilead consummated signed agreements with seven large Indian drug firms some months ago to manufacture and sell lower cost versions of sofosbuvir in 91 developing countries, but there are other firms who have no such constraints.Doctors Without Borders noted a study done at Liverpool University that showed sofosbuvir could be produced for as little as $101 for a full regimen.Previously: Gilead licenses Sovaldi to Indian firms (Sept. 15, 2014)
India
Zafgen's Beloranib works by blocking MetAP2, an enzyme involved in fatty acid production, thereby decreasing lipid production in the liver and fat storage while increasing metabolism
also met them at JPMorgan, jan 2015, talk of a whole new period of excitement in cholesterol, a new age for the field, interesting to see what pcsk9s will do to arouse interest, then how oral,less expensive treatments could fill the void after statins, for both statin intolerant pts and in add on situations for pts who still need lowering
what's this tech all about? CRISPR-Cas9 - is this just the best gene editing method?
loads of investment going into CAR-T: this tweet
PropThinker ‏@PropThinker
Collectively, CAR-T valued at over $9 billion by public markets (smidcaps). $JUNO $KITE $ALCLS $BLCM
Here's to this stuff staying safe. ;)
PropThinker ‏@PropThinker 6m6 minutes ago
@PropThinker $9B not even close if you throw in $NVS and get ambitious with $ZIOP/ $XON, $SRNE, etc
Flu
antivirals - Tamiflu, Relenza and Rapivab - note controversy on
5thirty8 - 1/21/14
--discrepancy between the CDC’s assertion that the flu drugs can prevent complications, hospitalizations and perhaps deaths, and the FDA’s insistence that the drugs have only been shown to cut the amount of time that symptoms persist comes down to how they weigh the evidence ---All three antiviral medications are designed to inhibit neuraminidase, an enzyme that influenza viruses need to release viral particles from infected cells. ... could stem the spread of the flu, making them vital tools for controlling epidemics. (This is why the U.S. has reportedly spent about $1.5 billion stockpiling Tamiflu.)....however controversial....And if the drugs are simply reducing fevers and making people feel better via some other mechanism, then it’s possible they’re nothing more than expensive alternatives to acetaminophen and ibuprofen, which alleviate aches and reduce fevers. (Tamiflu retails for about $130, Relenza goes for about $67, and Rapivab costs about $1,000.) - you need to take them in the first 48 hours from the onset of symptoms.
Intrexon ($XON) and Ziopharm ($ZIOP) are cutting in on the fervor over a new class of immunotherapies for cancer, striking a deal with the University of Texas' MD Anderson Cancer Center.....Under the deal, the pair will give MD Anderson $100 million for a CAR-T technology, made through a process in which scientists remove T cells from a patient's blood and equip them with targeting mechanisms called chimeric antigen receptors (CARs) ---maybe a safer mech? uses nonviral gene transfer system to get those modified T cells to their targets, in contrast to leading CAR-T therapies from Novartis ($NVS), Juno Therapeutics ($JUNO), Kite Pharma ($KITE) and others. That presents some safety advantages, researchers say, as MD Anderson's approach has thus far avoided some of the dangerous immune responses that have afflicted rival CAR-T programs
"pharmagedon" -- a slow down in dtc marketing? but trending back up?
Adherence
gamification works - making it a game to take you pill -a company called healthprize
others calling it quits...these existing treatments? that must be getting very little use?
Merck (MRK) plans to withdraw its hepatitis C medicine, Victrelis (boceprevir), from the U.S. market by the end of this year due to declining demand in the wake of the Gilead Sciences (GILD +1.1%) juggernaut. Victrelis will remain available internationally.Vertex Pharmaceuticals (VRTX +0.4%) pulled its offering, Incivek (telaprevir) in August for the same reason and exited the hepatitis arena.Merck is not giving up yet. It plans to file an NDA by mid-year for an all-oral ribavirin-free hep C regimen, grazoprevir/elbasvir.
Ebola
Novartis -Cosentyx (secukinumab) approved - expected to be one of the biggest drug launches of 2015, with potential sales this year of $133 million and in 2020 of $1.1 billion. - IL17
sunshine act -- transparency
elizabeth warren's proposed "swear jar" charge companies (only big ones with a $1bn blockbuster) 1% of their earnings(is that right? for off label marketing, etc --money would go to nih and fda?
disclosing all payments to physicians and medical institutions from drug companies
lilly's SGLT2 drug Jardiance (empagliflozin) and the even newer GLP-1 drug Trulicity (dulaglutide)---formulary spots for diabetes meds, no pricing war necessary--so rather than pricing war are they strinking deals with payers?
GAAP and non-GAAP - Generally accepted accounting principles (GAAP) -seeking alpha about celgene's reporting, not claiming abuse, just raises a red flag - Just about every company reports "adjusted" or non-GAAP earnings using the justification that it better represents the underlying business. And, if used judiciously, that is fine. However, if abused, the non-GAAP figures can be highly misleading. - One of the major sources of differences between GAAP and non-GAAP reporting comes in the form of paying the top brass with stock and derivatives. This so-called "share-based compensation" must be included in the GAAP reporting but it is not included in the non-GAAP adjusted figures.---As I've shown above, for a company such as Gilead, an investor can pretty much ignore the difference between GAAP and non-GAAP figures. One cannot ignore the difference for Celgene. GAAP earnings per share for Celgene will be more like $2.70 in 2014 and I estimate $3.60 in 2015. Thus on a GAAP basis, the company is trading at approximately 45x 2014 earnings and 34x 2015 earnings.

Celgene sports a pretty high premium and that adds valuation risk to the stock. Furthermore, the compensation package looks, quite frankly, excessive. I love the company and I'm confident that strong growth will be had for the next several years. However, investors should be cognizant of what goes on "under the hood" and Celgene might want to make itself a bit more like Gilead in that respect.
seeing an abundance of anti-obesity devices...like Aspire's ..Bariatrics's AspireAssist Aspiration Therapy--Screenshot courtesy of Aspire - has a port into the stomach that removes 1/3 of your meal 20 minutes after you eat....if you don't chew, pieces might be too big - will it clog??? what does the solution look like, does it come into a bag?
Devices
Retina
jan 2015 - more ipo hotness--Spark nails a $161M IPO to fund its 'breakthrough' gene therapy for --inherited retinal dystrophies
Vyvanse® (lisdexamfetamine dimesylate) Capsules (CII), the first and only medication for the treatment of moderate to severe binge eating disorder (B.E.D.)
Insomnia
merck's BELSOMRA® (suvorexant) - targets Orexin is one of the many neurotransmitters in the brain involved in promoting wakefulness, and BELSOMRA selectively blocks orexin receptors. In doing this, BELSOMRA is thought to suppress wake drive in the brain
Generics
PFE buying hospira for 17bn
Cancer vaccines
-Dendreon's Provenge - for prostate cancer, all sorts of issues
-poor sales and cost control
-launch was delayed for extra study - launched finally in late 2011
-priced the complex, personalized treatment at an eye-opening $93,000
-surveys unveiled some deep-seated skepticism among specialists that the drug's ability to extend survival times was worth the cost
-Then J&J's ($JNJ) Zytiga won approval for late-stage use, setting it up for a subsequent OK for the pre-chemo crowd. And more recently Medivation's ($MDVN) Xtandi came along to add to oral alternatives many physicians and patients clearly preferred.
was bought by valeant - $296 million in cash, entering into a stalking-horse agreement that a bankruptcy court must now approve

PEGASUS-TIMI 54 study, a large scale outcomes trial involving over 21,000 patients, successfully met its primary efficacy endpoint. The study assessed BRILINTA® (ticagrelor)
Sandoz for Filgrastim, which is biosimilar to Amgen’s Neupogen®. Approved February 20, 1991, Neupogen® is prescribed for patients receiving chemotherapy to reduce the risk of infections by treating neutropenia, a condition characterized by an abnormally low count of a type of white blood cell called neutrophils that helps fight off bacterial and fungal infections. It also brought Amgen $1.4 billion in sales last year.
The antibody experts at Regeneron ($REGN) believe their in-development allergy treatment could be the next big thing at the Big Biotech, rolling toward the market with a potential blockbuster.

The injection, dupilumab, targets two proteins, interleukin-4 and interleukin-13, that play a key role in the inflammatory process, and Regeneron believes it could treat a wide range of allergic ailments with a common root. Like the awaiting-approval cholesterol drug alirocumab, dupilumab is partnered with Sanofi ($SNY), and Regeneron says it could have similar commercial potential.
Allergy
http://www.forbes.com/sites/matthewherper/2013/05/29/as-statins-soar-use-of-other-cholesterol-medicines-declines/
...That’s why statins dominate the cholesterol drug market. In fact, 57% of prescriptions for cholesterol medicines are for two statins: simvastatin, once sold by Merck under the brand name Zocor, and atorvastatin, until recently sold by Pfizer PFE -0.93% under the brand Lipitor. Both are cheap generics. Between 2011 and 2012, when atorvastatin went generic and cheaper versions became available, use of the drug increased 20%, largely at simvastatin’s expense.
...For other medicines the data have been less kind. The biggest drop in total prescriptions over this time-frame has been ezetimibe, sold by Merck under the brand names Zetia (just ezetimibe) and Vytorin (which combines ezetimibe with simvastatin). In 2007 Merck’s own study failed to show that adding ezetimibe to simvastatin prevented thickening of the neck arteries on ultrasound scans, leading some doctors, like Krumholz, to question whether ezetimibe has a benefit. Combined prescriptions of both forms of ezetimibe dropped 68% between 2007 and 2012. Merck is launching a new combo pill, Liptruzet, that combines atorvastatin and ezetimibe in the hopes of increasing sales.
Statins
Co Execs
2015 - Olivier Brandicourt CEO effective April 2, choosing an outsider to replace ousted CEO Christopher Viehbacher
Some of the big ones
These three were the big 2009 year
Pfizer - Wyeth - $68bn
Merck - Schering-Plough $41b
Roche - Genentech - $46.8bn

Others since
Pfizer trying for AZ
Valeant - Medicis
AZ - Ardea
BMS and AZ teaming up for Amylin
Abbvie trying for Shire?
Gilead - Pharmasset
Shire - NPS, 2015 $5b
Valeant - Allergan denied --- Actavis - Allergan for $66bn nov 2014
Valeant for Salix - $14.5 bn, 2/23/15
Amgen for Onyx for $10bn to get Krypolis
Abbvie for pharmaccylics - 21bn
Some of the big ones
most recently - BMS goes $800m for Flexus' IDO inhibitor tec - could total $1.25bn,
Ongoing, upcoming, potential, recent
scratch all that, because Abbvie is giong 21bn for half the rights to imbruvica
---xxxxPharmacyclics for $19bn - may be with JnJ, they have collaborated for years - work on Imbruvica ---

Imbruvica (imbrutinib)had already won FDA approval for treatment of patients with mantle cell lymphoma in 2013. In 2014, the approval was extended to patients with previously treated chronic lymphocytic leukaemia, and then widened to include treatment of CLL patients who carry a deletion in chromosome 17---Imbruvica is an easy-to-use pill that costs around $100,000 a year, avoids certain serious side effects of chemotherapy, and patients can stay on it for long periods of time -- drug has also made a billionaire of Chief Executive Officer Robert W. Duggan. Duggan owns 13.5 million shares, or 18 percent, of Pharmacyclics. The stock constitutes the bulk of his $3.2 billion net worth - $4.2 billion in estimated sales in 2019, according to an average of estimates by analysts.
Imbruvica “certainly has the potential of Gleevec-like revenue,” ---rally-administered, selective and covalent inhibitor of the enzyme Bruton's tyrosine kinase (BTK).
--some of his money goes to scientology - “I feel it is an honor and personal obligation to share my financial success with Scientology,” he wrote in a 2013 e-mail to Bloomberg New
ibrutinib - Imbruvica - for Chronic lymphocytic leukemia (CLL) who have received at least one prior treatment
Chronic lymphocytic leukemia (CLL) with 17p deletion
Waldenström's macroglobulinemia (WM)
---huge deal for this, Abbvie, 21bn to pharmacyclics, had been a jv btn pharmacyclics and jnj
BMS - Opdivo nivolumab to treat patients with metastatic squamous non-small cell lung cancer (NSCLC) -- really fast approval - three months ahead of the drug's June 22 PDUFA date, and just five days after BMS said FDA accepted the sBLA for review...
Lipitor (atorvastatin) and Crestor (rosuvastatin)
The FDA approves Sandoz's (NYSE:NVS) Zarxio, a biosimilar to Amgen's (NASDAQ:AMGN) Neupogen (filgrastim), for the same indications as Neupogen.Zarxio is approved for the treatment of patients with cancer receiving myelosuppressive chemotherapy, patients with acute myeloid leukemia receiving induction or consolidation chemotherapy, patients with cancer undergoing bone marrow transplantation, patients undergoing autologous peripheral blood progenitor cell collection and therapy and patients with severe chronic neutropenia.The placeholder nonproprietary name for Zarxio is "filgrastim-sndz.
approved
3/6/15
Amgen laying off ~300, which were from Onyx acquistion -revealed that Kyprolis, the blood cancer drug at the heart of its roughly $10 billion acquisition of Onyx ---so laying people off right after they get success in trial? or approval? A move towards the commercials stage from the RnD?
Notable layoffs, closures, synergies...etc
Amgen reported that over a one-year period, 0.95% of patients treated with Repatha plus standard of care (SOC) experienced adjudicated CV events compared to 2.18% of patients given SOC alone (HR=0.47; 95% CI, 0.28, 0.78; p=0.003). The company also said Repatha plus SOC reduced LDL cholesterol by 61% compared to SOC alone (p<0.001) by week 12, with reductions sustained through week 48. The open-label extension study included 4,465 patients who participated in the Phase II OSLER-1 trial or Phase III OSLER-2 trial.
In the 2,341-patient Phase III ODYSSEY LONG TERM trial of Praluent to treat hypercholesterolemia, 1.7% of Praluent-treated patients experienced adjudicated major adverse cardiac events (MACE) vs. 3.3% of those receiving placebo (HR=0.52, 95% CI: 0.31, 0.90; nominal p<0.01). Praluent plus SOC also reduced LDL by 62% at week 24 vs. placebo plus SOC (p<0.0001), with reductions sustained through week 78.
Praluent's PDUFA date is July 24 and Repatha's is Aug. 27.
DATA for Repatha and Praluent - NEJM
march 20- big news for BIIB037, big stock bump, drug showed a 95% reduction in amyloid, --- on isue could be high levels of ARIA withhigh doses, high incidences of what are known as Amyloid-Related Imaging Abnormalities, or ARIA --has a name now, aducanumab
Big blockbuster for 2015
According to Thomson Reuters' 2015 Drugs to Watch report, as many as 11 blockbuster drugs (peak sales of at least $1B within five years) are expected to clear the regulatory process this year. This is a significant jump from 2014's tally of three (Gilead's (NASDAQ:GILD) Sovaldi and Zydelig; Glaxo (NYSE:GSK) and Theravance's (NASDAQ:THRX) Anoro Ellipta). In reverse order (forecasted 2019 consensus sales in parentheses):11. Novartis' (NYSE:NVS) Cosentyx (secukinumab) for psoriasis and psoriatic arthritis ($1.08B); 10. Sanofi's (NYSE:SNY) Toujeo (insulin glargine) for diabetes ($1.26B); 9. Otsuka Pharmaceutical (OTCPK:OTSKY) and Lundbeck's (OTCPK:HLUYY) Brexpiprazole for schizophrenia and depression ($1.35B); 8. Merck's (NYSE:MRK) Gardisil 9 HPV vaccine ($1.64B); 7. Amgen's (NASDAQ:AMGN) evolocumab for hypercholesterolemia/hyperlipidemia ($1.86B); 6. AbbVie's (NYSE:ABBV) Veikira Pak for hepatitis C (cleared 12/19/14) ($2.5B); 5. Vertex Pharmaceuticals' (NASDAQ:VRTX) lumacaftor plus ivacaftor for cystic fibrosis ($2.74B); 4. Pfizer's (NYSE:PFE) Ibrance (palbociclib) for breast cancer ($2.76B); 3. Novartis' LCZ696 for chronic heart failure ($3.73B); 2. Regeneron Pharmaceuticals' (NASDAQ:REGN) Praluent (alirocumab) for hypercholesterolemia ($4.41B) and 1. Bristol-Myers Squibb's (NYSE:BMY) Opdivo (nivolumab) for melanoma ($5.68B).

Novo Nordisk ($NVO) is finally ready to resubmit Tresiba, a long-acting insulin...alarming safety signals, and Novo kicked off a cardiovascular outcomes trial with the goal of amassing long-term data to demonstrate the insulin's tolerability. And waiting on full results would push Tresiba's potential launch back to 2017 at the earliest, allowing next-generation products from rivals Sanofi ($SNY) and Eli Lilly ($LLY) to get entrenched in the U.S. market.
Cystic Fibrosis
Vertex's Kalydeco - ivacaftor - taken every 12hrs, with fat containing food
improves action of CFTR - genes defects approved...CF gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R.
-->how many more are there?
this is 4 to 5% of pts, accroding to wiki
~$300k per yr
-approved in 2012
clonal neoplastic disorder of hematopoiesis, and is one of the myeloproliferative disorders. Production of cytokines such as fibroblast growth factor by the abnormal hematopoietic cell clone (particularly by megakaryocytes)[4] leads to replacement of the hematopoietic tissue of the bone marrow by collagen fibrosis, impairing the patient's ability to generate new blood cells and resulting in a progressive pancytopenia. However, the proliferation of fibroblasts and deposition of collagen is a secondary phenomenon, and the fibroblasts are not themselves part of the abnormal cell clone. Enlargement of the spleen commonly results in hypersplenism, which also contributes to causing pancytopenia, particularly thrombocytopenia and anemia. Myelofibrosis can result as a late complication of other myeloproliferative disorders, such as polycythemia vera or essential thrombocytosis. - wiki
a Janus kinase inhibitor with selectivity for subtypes JAK1 and JAK2 of this enzyme.[6][7] Ruxolitinib inhibits dysregulated JAK signaling associated with myelofibrosis. JAK1 and JAK2 recruit signal transducers and activators of transcription (STATs) to cytokine receptors leading to modulation of gene expression.
Vivus qsymia
Allergy
Interesting background to the allergy picture, fierce 4/1/15
5. Forget fighting over Flonase ads. GSK and J&J settle on fight for market share


GlaxoSmithKline ($GSK) and Johnson & Johnson ($JNJ) have settled a short-lived legal spat over GSK's allergy drug marketing claims--meaning that now, the only battle left will be the one for market share.

After claiming in a TV spot that its Flonase outperformed the No. 1 allergy pill--and controls 6 symptoms to its rival's one--Glaxo has reached a "mutually acceptable and amicable" agreement with competitor J&J, the terms of which are confidential, Reuters reports.

J&J, the maker of allergy hotshots Benadryl and Zyrtec, brought the suit earlier this month, claiming Glaxo made unsupported claims that would hurt those high-performing brands--even though they weren't named specifically. J&J argued that Zyrtec was the No. 1 allergy pill by sales, meaning consumers who saw GSK's spot would conclude it was inferior to Flonase.

GSK responded, bringing in Dr. Ran Kivetz, a marketing professor at Columbia University Business School to challenge those assertions.

"Different consumers are likely to rely on different constructs or beliefs when forming an inference (if any) regarding the identity," of the No. 1 leading allergy pill, he said in a court document. Consumers may identify the leader as "that brand or pill for which they have the highest brand awareness"--and arguably, that's Bayer's Claritin, he pointed out.

But the court fight is all over now, meaning it's time for both pharma giants to turn their attention back to OTC sales--likely top of mind for both drugmakers. Glaxo, which recently teamed up with Novartis ($NVS) to form an industry-leading consumer health joint venture, is gunning for a hefty share of the allergy pie after nabbing FDA approval for OTC Flonase last year.

And J&J, for its part, is gunning for a rebound at its McNeil consumer unit. Over the past few years, in the wake of major recalls, McNeil hasn't managed to get retailers fully stocked with its top consumer brands. Quality problems at a key plant forced McNeil to pull millions of packages of Motrin, Tylenol and Benadryl products, among others.
Shingles
GlaxoSmithKline ($GSK) is still awaiting late-stage results for its shingles vaccine, HZ/su, Cowen & Co. analysts believe the vaccine may just be better than Merck's Zostavax.
EBITDA---is an accounting measure calculated using a company's net earnings, before interest expenses, taxes, depreciation and amortization are subtracted, as a proxy for a company's current operating profitability, i.e., how much profit it makes with its present assets and its operations on the products it produces and sells, as well as providing a proxy for cash flow. - company's earnings before interest, taxes, depreciation, and amortization (commonly abbreviated EBITDA - example of this as a metric is where a company is priced for a buyout - 4/10/15 as Mylan is looking to buy Perrigo for $29n...its getting 26x EBITDA --as Fierce/Bloomberg note - and while that's high, it's lower than the 30-plus times EBITDA other suitors have been willing to put forth for targets since pharma's deal frenzy began
poison pill - shareholder rights plan, colloquially known as a "poison pill", is a type of defensive tactic used by a corporation's board of directors against a takeover. Typically, such a plan gives shareholders the right to buy more shares at a discount if one shareholder buys a certain percentage or more of the company's shares. The plan could be triggered, for instance, if any one shareholder buys 20% of the company's shares, at which point every shareholder (except the one who possesses 20%) will have the right to buy a new issue of shares at a discount. If every other shareholder is able to buy more shares at a discount, such purchases would dilute the bidder's interest, and the cost of the bid would rise substantially. Knowing that such a plan could be activated, the bidder could be disinclined to take over the corporation without the board's approval, and would first negotiate with the board in order to revoke the plan- if a company thinks its being bought...also part of a strategy...they might make a bid on someone else
PIPE - private investment in public equity-- raditional PIPE is one in which stock, either common or preferred, is issued at a set price to raise capital for the issuer. A structured PIPE, on the other hand, issues convertible debt----relative efficiency in time and cost of PIPEs, compared to more traditional forms of financing such as secondary offerings. In a PIPE offering there are less regulatory issues with the SEC and there is also no need for an expensive roadshow, lowering both the costs and time it takes to receive capital. PIPEs are great for small- to medium-sized public companies, which have a hard time accessing more traditional forms of equity financing. - from investopedia
FDA and regulatory
Kefauver–Harris Amendments to the Federal Food, Drug, and Cosmetic Act - With the stroke of a pen, a threadbare Food and Drug Administration (FDA) was given the authority to require proof of efficacy (rather than just safety) before approving a new drug — a move that laid the groundwork for the phased system of clinical trials that has since served as the infrastructure for the production of knowledge about therapeutics in this country. We often remember the Kefauver–Harris Amendments for the thalidomide scandal that drove their passage in 1962. But there is much we have collectively forgotten about Senator Estes Kefauver (D-TN) and his hearings on administered prices in the drug industry - NEJM article from 2012 - http://www.nejm.org/doi/full/10.1056/NEJMp1210007
CAR T-CELL DEALS

Institution/Company Date Partner Terms
University of Pennsylvania August 2012 Novartis Undisclosed

Celgene March 2013 Bluebird Bio, Baylor College of Medicine Unspecified upfront payment plus up to $225 million per product in option fees and milestone payments

Cellectis June 2014 Pfizer $80 million upfront plus up to $185 million per product and royalties
Cellectis January 2015 Ohio State University Undisclosed

Kite Pharma January 2015 Amgen $60 million upfront and up to $525 million per product in milestone payments, plus royalties on sales and IP licensing

Md Anderson January 2015 Ziopharm, Intrexon $100 million in stock and $15–20 million/year for 3 years
CAR T-CELL BIOTECH IPOs

Company Date Value
Kite Pharma June 2014 $134.1 million
Bellicum December 2014 $160 million
Juno December 2014 $264.6 million
Cellectis March 2015 $228 million
DEALS and IPOs in CAR-T
http://www.the-scientist.com/?articles.view/articleNo/42462/title/The-CAR-T-Cell-Race/
challenges in solid tumor -- biocentury - 4/21/15..
CAR T stocks fall on solid tumor data

CAR T data from Novartis AG (NYSE:NVS; SIX:NOVN) and the University of Pennsylvania demonstrated much of what's already known about the challenges of moving the technology into the solid tumor setting. A presentation at the American Association for Cancer Research meeting in Philadelphia on Sunday showed no complete or partial responders among five patients receiving CART-meso.
The product is an intravenous infusion of autologous T cells transduced to express a CAR directed against mesothelin in patients with recurrent, advanced mesothelin-expressing solid tumors.
There were some signs of efficacy, such as "the clearing of malignant cells in the pleural fluid of one patient" and "radiological and clinical evidence of stable to decreased burden of disease in one patient," according to an abstract from the UPenn presentation.
Solid tumors are typically more intractable than many blood cancers where CAR T products have shown strong response rates. Solid tumors create their own microenvironment and are heterogeneous and structurally complex.
The CART-meso T cells were transiently detectable in peripheral blood for up to 28 days post-infusion. In blood cancers, other CAR T products have shown persistence for more than a year.
In solid tumors the potential to hit the right target on the wrong cell makes it difficult to find a balance between T cell persistence and safety. The greater the persistence, the more likely patients will not relapse. But greater persistence increases the chance that T cells may ultimately find and destroy normal tissues with low levels of antigens.
As reported, the Novartis/UPenn product showed no off-tumor on-target toxicities. The product did travel to tumor sites as well as off-tumor on-target sites.
In a statement to BioCentury, Novartis noted the study was not designed to show efficacy, but rather safety and feasibility of the treatment.
The data put downward pressure on CAR T therapy developers Juno Therapeutics Inc. (NASDAQ:JUNO) and Kite Pharma Inc. (NASDAQ:KITE). Juno lost $8.76 (14%) to $55.90 on Monday, while Kite dipped $6.38 (10%) to $58.68.
Both Kite and Juno are studying CAR T therapies in solid tumors, but their most advanced programs are treatments for blood cancers
interesting take by Sony-->basically saying that when i comes to cx, it will be too complicated for PBMs to restrict, molecules will have different data sets, in different combinations, for different speicific cancers...so strong tactics like exclusions lists will be difficult for them to use, perhaps softer ones like prior authorizatoin and step editing
Anti-PD-1s from Merck (NYSE:MRK) and Bristol-Myers Squibb (NYSE:BMY) have experts debating the likelihood that manufacturers will offer discounts in exchange for exclusive PBM status. Both Merck's Keytruda (pembrolizumab) and BMS' Opdivo (nivolumab) are high-priced drugs considered roughly equivalent in outcomes in melanoma, but experts agreed that as combination therapies come into play and additional indications are approved, pharmacy benefit managers (PBM) exclusion lists will be a less-likely cost control tactic...
Insider trading

massive New Yorker article
The Empire of Edge
Steven Cohen of S.A.C Capital
bapineuzumab by Elan and Wyeth
Dr Sid Gilman presenting negative data on it in 2008 - passed info to Cohen
Cohen had a $700m position in the two companies, liquidated...shorted, made $275m
the drug was carried on some with JnJ and PFE, but they've announced no longer continuing it aorund 2013
Mathew Martoma - key player at SAC
and Gerson Lehrman Group



Vaccine big players
Fierce - Aug 2015 report - top 5 vaccines cos
Merck - $6.25bn 2014 sales
Gardasil -for HPV - they now are up to the Gardisil 9, so they've added 5 new strains - potential to block 90% of cervical cancers - makes $2bn --
other vaccines include M-M-R, Varivax and ProQuad, which protect against measles, mumps, rubella and varicella. The trio brought in $1.39 billion in 2014. Merck also markets Zostavax, the only shingles vaccine approved for human use
Sanofi- $5.84bn
gearing up for the launch of its decades-in-development dengue vaccine - with a 3 or 4 billion potential patient pool!
Also significant flu vaccine - sales have been up
they get a chunk of Gardisil 9 in Europe

GSK $5.26bn
-Leading vaccine by far was Pediarix, raking in £828 million ($1.23 billion) in sales for Diphtheria; Tetanus; Pertussis/whooping cough; Hepatitis B; Polio
-hepatitis vaccines, with £559 million ($872 million) in sales
-Synflorix for Pneumococcal infection, with £398 million ($621 million)
Cervarix, GSK's competitor to Gardasil, brought in £118 million ($184 million)

They might move up on this list though, with Vaccines from the Novartis asset swap, they'll get Bexsero for meningitis b

-As for the days ahead, GSK's malaria jab, RTS,S or Mosquirix, received a positive opinion from the EMA, its Ebola candidate is in Phase II trials with and without a booster, and its shingles candidate recently posted superior efficacy to Merck's ($MRK) Zostavax, the only shingles vaccine approved for use in the U.S. and EU.

#1
#2
#3
Pfizer - $4.48bn
for Pneumococcal infection - world's best-selling jab, Prevnar 13, which raked in $4.29 billion in 2014 sales and is anticipated to grow to $5.83 billion in sales by 2020.

they say they plan to move away from depency on the prevnar - a cancer vaccine platform--first focusing on prostate cancer but with the potential for "large number of important cancers"--a human cytomegalovirus candidate, a cholesterol-fighting jab, vaccines each for S. aureus and C. difficile and others. To add to that, the company late last year won FDA approval for its meningitis B vaccine Trumenba, beating out Novartis' Bexsero and winning the two-horse race for the first approved meningitis B vaccine in the U.S
#4
Novartis - $1.54bn
Stepping away from vaccines biz - trading away the bulk of its vaccines portfolio for GlaxoSmithKline's ($GSK) oncology unit and sealing its exit from the vaccine space by finalizing the sale of its flu vaccines unit to CSL -- For Novartis, the asset swap with GSK was nothing but good news. Its vaccines unit, formed in 2006 from the company's buyout of Chiron, posted a $525 million operating loss in 2014.
#5
what does a cart pipeline look like now?
Chronic Obstructive Pulmonary Disease
GSK's Breo Ellipta - which theyy hoped would replace the sales from advair once it went generic- advair expected to be engulfed by genereics by 2020 - Breo was left looking remarkably similar...they hoped to show a big result in high risk pts mortality
could talk about pulmatrix's effort here in COPD
SMA
Gene therapy biotech AveXis got backing from Roche Ventures - scAAV9.CB.SMN, a Phase I gene therapy for SMA Type 1. -- Roche is big in the area - Roche Venture Fund's investment follows its parent company's sweeping approach to SMA, including a 2011 partnership deal with PTC Therapeutics ($PTCT) worth up to $490 million and a January buyout of Trophos for as much as $545 million --- others include Isis Pharmaceuticals ($ISIS) posted an encouraging update from its ongoing midstage program earlier this summer, pressing forward with a Biogen ($BIIB)-partnered treatment. And Pfizer ($PFE) nixed a $70 million collaboration with Repligen ($RGEN) in January,
ThePAAS conference that i went to...certainly the idea that pharma has had a history of "fits and starts" .... at this point, with tech companies moving in, is adherence/tech/wearables someting better suited for tech co's to move more rapdily on?
an interesting tech, wearable sensor, pings when it detects that the pill has entered your stomach...here's an example from Proteus partnered with otsuka....The companies' device embeds Proteus' ingestible sensor into Otsuka's Abilify med for severe mental illnesses including schizophrenia, allowing patients, physicians and caregivers to monitor how an individual takes the drug. Proteus' sensor sends a signal to a wearable patch after it reaches the stomach, and the patch then records and time-stamps the information, sending it back to a mobile phone or Bluetooth device. The sensor also records other patient metrics such as rest, body angle and activity patterns, giving a better picture of what a patient is doing while they're taking the med and potentially improving adherence. --- but isn't this kind of creepy too....could certainly be useful for convicts, or schizo people who might be in and out of jail/institusions....Proteus said it would team up with Oracle to integrate its sensor into the company's clinical trial management software system
Non-Small Cell Lung Cancer
This is the most common type of lung cancer. About 85% of lung cancers are non-small cell lung cancers.
---Squamous cell carcinoma, adenocarcinoma, and large cell carcinoma are all subtypes of non-small cell lung cancer.
Small Cell Lung Cancer
Small cell lung cancer is also called oat cell cancer. About 10%-15% of lung cancers are small cell lung cancers.
----This type of lung cancer tends to spread quickly.
Lung Carcinoid Tumor
Fewer than 5% of lung cancers are lung carcinoid tumors. They are also sometimes called lung neuroendocrine tumors.
---- Most of these tumors grow slowly and rarely spread.
in NSCLC - AZ and Clovis racing - AZD9291 vs rociletinib (CO-1686) ---"Heading into WCLC, feedback from MEDACorp key opinion leaders (KOLs) was that if AZD9291 maintained its 3-month PFS advantage over rociletinib as highlighted at ECLC and ASCO they would use AZD9291 in 80-90% of T790m + patients," noted Leerink's Seamus Fernandez. "With these data, most KOLs still prefer AZD9291, but the impact frequency of rash with AZD9291 vs. diabetes with rociletinib suggests that AZD9291 may not dominate the market to the degree previously assumed."....Clovis is also advancing rucaparib, a rival to AstraZeneca's newly-approved Lynparza.
Lung Cancer
Merck KGaA is trying to bring cladribine--the multiple sclerosis pill scuttled by regulatory rejections on both sides of the Atlantic four years ago--back from the dead.
PML issues- serious AE - but this happens with any drug that knocks down t-cells
From Forbes, in Nov 2015 issue, convo with Ian Read on pricing....That’s part of the reason the drug industry has been in a decades-long process of consolidation, in which Pfizer has been the biggest acquirer. It got Lipitor from its $110 billion purchase of Warner-Lambert in 2000 and arthritis pill Celebrex from the $60 billion purchase of Pharmacia in 2003. Mergers disrupt research, and Kindler was reluctant to do another. But as Pfizer’s drugs failed and shares approached 15-year lows, he bought Wyeth in January 2009 for $68 billion.
Some historical oncology things to know
Paclitaxel
is a drug used to treat ovarian, breast, lung, pancreatic and other cancers.[2] It and docetaxel represent the taxane family of drugs
--discovered beginning in 1962[3] as a result of a U.S. National Cancer Institute-funded screening program; being isolated from the bark of the Pacific yew
-- Developed commercially by Bristol-Myers Squibb, the generic name has changed to "paclitaxel" with a trademark becoming Taxol. Other trademarks include
Abraxane
. Clinicians sometimes use the abbreviation "PTX" for paclitaxel, which is discouraged because it is not a unique identifier.
Albumin-bound paclitaxel (trade name Abraxane, also called nab-paclitaxel) is an alternative formulation where paclitaxel is bound to albumin nano-particles
Synthetic approaches to paclitaxel production led to the development of
docetaxel
. Docetaxel has a similar set of clinical uses to paclitaxel and is marketed under the name of Taxotere
-interesting/intrigue that includes congressional hearings on NIH, transfer from gov, naming of taxol...etc
Provenge...interesting story of shortselling that includes Jim Cramer, Michael Milken - organized crime ties...all according to deepcapture.

where does the fact that manufacturing became an issue come in? this is all preapproval
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