Sunday, 26 June 2016

WO 2016092561, Ivacaftor, New patent, Laurus Labs Pvt Ltd


WO-2016092561, Ivacaftor, NEW PATENT
Novel polymorphs of ivacaftor, process for its preparation and pharmaceutical composition thereof
Laurus Labs Pvt Ltd
LAURUS LABS PRIVATE LIMITED [IN/IN]; Plot No. DS1, IKP Knowledge Park, Genome Valley Turkapally, Shameerpet Mandal, Ranga District Hyderabad 500078 (IN)

Ram ThaimattamVenkata Srinivasa Rao DAMAVenkata Sunil Kumar IndukuriSeeta Rama Anjaneyulu GORANTLA,Satyanarayana ChavaLess «
ApplicantLaurus Labs Private Limited

DAMA, Venkata Srinivasa Rao; (IN).
INDUKURI, Venkata Sunil Kumar; (IN).
GORANTLA, Seeta Rama Anjaneyulu; (IN).
CHAVA, Satyanarayana; (IN)
Novel crystalline forms of ivacaftor (designated as forms L1 to L14), processes for their preparation and composition comprising them are claimed.
Vertex, in research collaboration with Cystic Fibrosis Foundation Therapeutics, had developed and launched ivacaftor.
Ivacaftor, also known as N-(2,4-di-tert-butyl-5-hydroxyphenyl)-l,4-dihydro-4-oxoquinoline-3-carboxamide, having the following Formula I:
Formula I
Ivacaftor was approved by FDA and marketed by Vertex pharma for the treatment of cystic fibrosis under the brand name KALYDECO® in the form of 150 mg oral tablets.
WO2006/002421 publication discloses modulators of ATP-binding cassette transporters such as ivacaftor. This patent generally discloses a process for the preparation of modulators of ATP-binding cassette transporters such as quinoline compounds; however, specific process for the preparation of ivacaftor and its solid state details were not specifically disclosed.
WO2007/079139 publication discloses Form A, Form B and amorphous form of ivacaftor characterized by PXRD, DSC and TGA and process for their preparation. Further this publication discloses ethanol crystalate of ivacaftor in example part.
WO2009/038683 publication discloses the solid forms of ivacaftor, which are designated as Form-I (2-methylbutyric acid), Form-II (propylene glycol), Form-HI (PEG400.KOAc), Form-IV (lactic acid), Form-V (isobutyric acid), Form-VI (propionic
acid), Form- VII (ethanol), Form- VIII (2-propanol), Form-IX (monohydrate), Form-X (besylate Form A), Form-XI (besylate Form B), Form-XII (besylate Form D), Form-XIII (besylate Form E), Form-XIV (besylate Form F), Form-XV (besylate (2: 1)), Form-XVI (besylate mono hydrate). This publication also discloses the characterization details like PXRD, DSC and TGA for the above forms and process for their preparation.
WO201 1/1 16397 publication discloses crystalline Form C of ivacaftor, process for its preparation and pharmaceutical composition comprising the same. Also discloses characterization details of Form C, such as PXRD, IR, DSC and 13CSSNMR.
WO2013/158121 publication discloses solvated forms of ivacaftor, which are designated as Form D (acetonitrile or acetonitrile/water (75/25) solvate), Form E (Methyl ethyl ketone (MEK), MEK/water (90/1), MEK/water (90/10), MEK/water (80/20) solvate), Form F (acetonitrile/water (75/25) solvate), Form G (isopropyl acetate solvate), Form H (isopropyl acetate/water (95/5) solvate), Form I (MEK solvate), Form J (MEK/water (99/1) solvate), Form K (MEK or MEK/water (99/1) or MEK/water (90/10) or MEK/water (80/20) solvate), Form L (isopropyl acetate/water (95/5) solvate), Form M (MEK or MEK/water (99/1) solvate), Form N (MEK water (90/10) or MEK/water (80/20) solvate), Form O (MEK or MEK/water (99/1) solvate), Form P (MEK water (90/10) or MEK water (80/20) solvate), Form Q (MEK/water (80/20) solvate), Form R (acetonitrile solvate), Form S (MEK/water (80/20) solvate), Form T (isopropyl acetate/water (95/5) solvate), Form W (acetonitrile/water (90/10) solvate), Form XX (from 10% water/ acetonitrile) and hydrate B (hydrated form). This patent further discloses characterization details like PXRD and TGA for the above forms and process for their preparation.
WO2014/118805 publication discloses crystalline forms of ivacaftor designated as Form D, Form E, Form El, Form G and Form G'; amorphous ivacaftor designated as Form I and Form II; crystalline ivacaftor solvates such as n-butanol solvate, methanol solvate, propylene glycol solvate, DMF solvate, THF solvate, DMF:ethylacetate solvate. This publication further discloses the process for the preparation of said forms along with their characterization details.
WO2015/070336 publication discloses polymorphic form APO-I and MIBK solvate of ivacaftor along with its characteristic PXRD details, process for its preparation and pharmaceutical composition comprising them.
CN 104725314A publication discloses ivacaftor new polymorph D, which is obtained by crystallization of ivacaftor from acetonitrile/water. This publication further discloses characteristic details such PXRD, IR and DSC of ivacaftor new polymorph D.
Polymorphism is the occurrence of different crystalline forms of a single compound and it is a property of some compounds and complexes. Thus, polymorphs are distinct solids sharing the same molecular formula, yet each polymorph may have distinct physical properties. Therefore, a single compound may give rise to a variety of polymorphic forms where each form has different and distinct physical properties, such as different solubility profiles, different melting point temperatures and/or different x-ray diffraction peaks. Since the solubility of each polymorph may vary, identifying the existence of pharmaceutical polymorphs is essential for providing pharmaceuticals with predictable solubility profiles. It is desirable to investigate all solid state forms of a drug, including all polymorphic forms and solvates, and to determine the stability, dissolution and flow properties of each polymorphic form.
Polymorphic forms and solvates of a compound can be distinguished in a laboratory by X-ray diffraction spectroscopy and by other methods such as, infrared spectrometry. Additionally, polymorphic forms and solvates of the same drug substance or active pharmaceutical ingredient, can be administered by itself or formulated as a drug product (also known as the final or finished dosage form), and are well known in the pharmaceutical art to affect, for example, the solubility, stability, flowability, tractability and compressibility of drug substances and the safety and efficacy of drug products.
The discovery of new polymorphic forms and solvates of a pharmaceutically useful compound, like ivacaftor, may provide a new opportunity to improve the performance characteristics of a pharmaceutical product. It also adds to the material that a formulation scientist has available for designing, for example, a pharmaceutical dosage form of a drug with a targeted release profile or other desired characteristic. New polymorphic forms of the ivacaftor have now been discovered and have been designated as ivacaftor Form-Ll, Form-L2, Form-L3, Form-L4, Form-L5, Form-L6, Form-L7, Form-L8, Form-L9, Form-LlO, Form-Ll 1, Form-Ll 2 A, Form-Ll 2B, Form-Ll 3 and Form-Ll 4.
EXAMPLE 1 : Preparation of Ivacaftor Form-Ll
A suspension of ivacaftor ethanolate (5 g) in n-heptane (200 mL) was heated to 95-100°C and stirred for 5 hrs at the same temperature. Then the reaction mixture was cooled to 25-35°C and stirred for an hour. The solid obtained was filtered, washed with n-heptane and suck dried. The wet solid was further dried at 60-65°C for 16 hrs under vacuum yielded ivacaftor Form-Ll . The XRPD is set forth in Figure- 1.
In a similar manner, ivacaftor Form-Ll was prepared from different solvates of ivacaftor in place of ivacaftor ethanolate as input using the following conditions;
Ivacaftor cyclopentyl methyl ether (0.5 g) n-heptane (20 mL) 50°C/8 hr
Ivacaftor methyltertiarybutyl ether (0.5 g) n-heptane (20 mL) 50°C/8 hr
Laurus Labs: A hot startup in the pharma sector
Dr Satyanarayana Chava
Chief executive officer (CEO)
When Dr Satyanarayana Chava started Laurus Labs in 2007, he invested nearly Rs 60 crore of his own money into it. His confidence in its success was neither bravado nor bluster, but defined by his knowledge of the pharmaceutical industry. Eight years on, the Hyderabad-based company is on track to reach revenues of Rs 2,000 crore by the end of FY2016.
Chava, now 52, has more than two decades of experience in the pharmaceutical industry; in his last job, he was chief operating officer (COO) of the successful startup, Matrix Laboratories. Of his 10 years there, he says with pride, “I never skipped a promotion and got to work in all departments.” His dedication, coupled with a sound understanding of what it takes to start a pharmaceutical company, is what makes Laurus Labs among the hottest startups in this sector.
Initially, Chava planned the business around research and development (R&D). He wanted Laurus Labs to focus on contract research and make money from royalties. “In India, companies start with manufacturing and then get into R&D,” he explains. “I did it the other way round.” He focussed his fledgling company’s resources on developing formulations for medicines, and licensed them to other pharmaceutical players. In the early months, Laurus Labs had 10 people in manufacturing and 300 in R&D.
In June 2007, Aptuit, a US-based contract research organisation (CRO), signed it on for a $20 million (then Rs 80 crore) contract. But despite this injection of funds, Chava was unable to sustain his original idea of developing technologies for other companies. At the time of the Aptuit deal, Laurus Labs’s annual revenues were not even $20,000 (Rs 8 lakh at the time). In 2008, Chava decided to start manufacturing active pharmaceutical ingredients (API), which, as the name suggests, are chemicals or key ingredients in drugs required to make the medication work. His early investment into R&D benefitted Laurus Labs; it maintains a large repository of research-based knowledge that forms the bedrock of any successful pharmaceutical business.
Today, it is a key manufacturer supplier of APIs and holds its own against better-known competitors like US generic drug giant Mylan, which, incidentally, acquired a controlling stake in Matrix around the time Chava founded Laurus Labs. It has also carved a niche for itself by supplying antiretroviral or ARVs (used to fight infections caused by retroviruses like HIV) and oncology drugs. And despite being a relatively new player, its clients include giants like Pfizer, Teva Pharmaceutical Industries and Merck.
The person behind it
A Master’s degree in chemistry was never on the cards for Chava. In the early 1980s, the best students usually studied physics, and he had planned to do the same. But when he went to his college in Amravati (Andhra Pradesh) to enroll, his elder sister’s friend suggested he study chemistry too. Chava took up the subject on a whim. He ended up liking chemistry so much so that in his final year he topped his batch despite not having written one out of the four required papers. He went on to complete his PhD in the subject in 1991.
Upon graduating, he was hired by Ranbaxy Laboratories in Delhi as a researcher. In those early years itself Chava knew he’d spend a lifetime in the industry. He enjoyed the work and gained valuable experience as a young researcher in what was then India’s finest pharmaceutical company.
But through his years in the industry, Chava was conscious of the fact that he needed to broaden his experience outside of research. His stint at Matrix Laboratories afforded him that opportunity. As it was a startup, he was able to rise through the ranks quickly and got the opportunity to work in key departments from sales and marketing to finance and accounts. Within eight years of joining Matrix, he became its COO.
This experience was to come in handy when, due to differences with the board—he refused to elaborate on this—he decided to leave Matrix and set up Laurus Labs. And though he is the company’s chief executive officer (CEO), Chava remains true to his calling as a chemist. He has strived to build an organisation that is not very hierarchical. It is not uncommon to see him interacting with the chemists in the company and discussing formulations with them—something unheard of in an industry where most CEOs are from a sales and marketing background.

Chandrakanth Chereddi
VP Synthesis Business Unit
Prior to his current assignment at Laurus Labs India, Chandra headed the Project Management division for all scientific projects at the Laurus R&D center. Chandra previously worked for McKinsey & Company in India as a member of the healthcare practice and at Google Inc. as a software engineer in Google’s Mountain View, CA office. Chandra holds a BE from the College of Engineering, Osmania University, Hyderabad, and MS from University of Illinois at Urbana-Champaign, and an MBA from Indian School of Business, Hyderabad.

EP 03031800, New patent, Miglustat, Navinta LLC


Gauchers disease type I; Niemann Pick disease type C
EP-03031800, Process for the preparation of high purity miglustat
Navinta, LLC Shah, Shrenik K. ; Kharatkar, Raju Mahadev ; Bhatt, Chiragkumar Anilkumar ; Kevat, Jitendra Bhagwandas
The present invention provides a process for the preparation and isolation of crystalline miglustat without the use of a column chromatography or ion exchange purification. The crystalline miglustat has a high purity and a melting point of 128 °C and an endothermic peak is 133 °C.
Process for preparing and isolating crystalline form of miglustat with a high purity is claimed. Represents a first PCT filing from the inventors on miglustat. Actelion, under license from Oxford GlycoSciences (OGS; then Celltech, now UCB), which licensed the compound from GD Searle & Co, has developed and launched miglustat.
Product patent WO9426714, will expire in the US in 2018.
Kharatkar is affiliated with Sterling Biotech, Bhatt is affiliated with Intas and Kevat is affiliated with Orchid Chemicals & Pharmaceuticals.
INVENTORS   Shah, Shrenik K.Kharatkar, Raju Mahadev; Bhatt, Chiragkumar Anilkumar; Kevat, Jitendra Bhagwandas
About Navinta
Navinta, LLC in Ewing, N.J. is a technology driven Pharmaceutical Company that focuses on novel routes of synthesis of new and existing drug molecules, complex pharmaceutical ingredients, novel formulations of liquid dosage form, novel oral dosage form, novel injectable dosage form and implantable drug delivery devices. Navinta has currently at least fifteen (15) patents granted or pending with the United States Patent and Trademark Office.

Miglustat is a potent inhibitor of glycosyltransferase. It is primarily used in the treatment of Gaucher's disease. Miglustat is chemically known as N-butyl-1,5-dideoxy-1,5-imino-D-glucitol of formula (I) and is sometimes referred as N-butyl-1-deoxynojirimycin. Miglustat is a white to off-white crystalline solid with a melting point of 125-126° C. Its empirical formula is C10H21NOand has a molecular weight of 219.28 g/mol.
      Miglustat belongs to the class of azasugars or iminosugars. Ever since the discovery of iminosugars in the 1960s, iminosugars have been subject of extensive studies in both the organic chemistry and biochemistry fields. Iminosugars are polyhydroxylated alkaloids, which may be described as monosaccharide analogues with nitrogen replacing oxygen in the ring. A well-known member of this extensive family of compounds is 1-deoxynojirimycin of formula (II).
      1-Deoxynojirimycin was initially synthesized in a laboratory. Subsequently, 1-deoxynojirimycin was isolated from natural sources, such as from leaves of mulberry trees and certain species of bacteria. 1-Deoxynojirimycin was shown to be an enzyme inhibitor.
      Further research on 1-deoxynojirimycin analogs revealed that N-alkylated derivatives of 1-deoxynojirimycin exhibited greater biological activity than 1-deoxynojirimycin. Among them, N-butyl-1-deoxynojirimycin or miglustat of formula (I), was identified as a very potent inhibitor of glycosyltransferase. Miglustat was later approved by the FDA for human use.
      Preparation of azasugars has been a very active area of research for a long time. A seminal synthesis of the compounds of formulas (I) and (II) by double reductive aminations of 5-keto-D-glucose was developed by Baxter and Reitz (J. Org. Chem. 1994, 59, 3175). This method was later refined by Matos and Lopes (Synthesis 1999, 571), in which tetra-O-benzyl-glucose was used as a starting material. Synthesis of miglustat can be traced back to 1977, when chemists from Bayer reported a synthesis of miglustat from 1-deoxynojirimycin and patented in U.S. Pat. No. 4,639,436. Other variations of this general scheme have also appeared in patents and non-patent literature, for example, U.S. Pat. No. 8,802,155 and U.S. Application Publication No. 2014/0243369.
      A major drawback of those protocols is that all of them require the use of ion-exchange resins for purification of miglustat. In those protocols, an aqueous solution of miglustat obtained after running an ion-exchange column was concentrated to isolate miglustat. Due to the presence of four hydroxyl groups and a tertiary amine moiety in its chemical structure, miglustat is extremely hydrophilic. Thus, isolation of miglustat from an aqueous solution is quite challenging. In particular, it was very difficult to remove diastereomers and inorganic impurities formed during the reactions from miglustat by those protocols. Sometimes a second chromatographic purification was required to separate these impurities from miglustat. As a result, the yields of miglustat were generally low. The requirement to use a column purification (e.g. ion exchange column, flash column chromatography) further limits the scale of miglustat that could be prepared.

      Scheme 1 is a synthetic scheme of miglustat in accordance with one embodiment of the invention:
      As depicted in scheme 1, the method of preparing miglustat may include the steps of: (1) providing or synthesizing a compound of formula (V); (2) conducting a reductive amination to provide a compound of formula (VI); (3) performing a hydrogenation reaction; and (4) isolating a free base miglustat.
      The starting material, 2,3,4,6-tetra-O-benzyl-1-deoxynojirimycin hydrochloride of formula (V) may be prepared by following the methods described in Organic Process Research and Development, 2008, 12, 414-423.
Example 1
Synthesis of 2, 3, 4, 6-tetra-O-benzyl-N-butyl-1-deoxynojirimycin hydrochloride of Formula (VI)
To a solution of 2, 3, 4, 6-tetra-O-benzyl-1-deoxynojirimycin hydrochloride (V) (prepared as in Organic Process Research & Development, 2008, 12, 414-423) (45 g, 0.08 mol) in 1575 mL of methanol, n-butyraldehyde (21.6 g, 0.24 mol) and sodium cyanoborohydride (25.2 g, 0.4 mol) were added and stirred. The reaction was maintained under stirring at a temperature from about C. to about C. After the completion of the reaction, the reaction was quenched by adding 765 ml of 10% HCl in methanol, while keeping the temperature between C. to C. The reaction mass was cooled to C. to C. and the resulting precipitate solids were filtered. The filtrate was treated with aqueous HCl and the solid formed was filtered, suspended in 1 N HCl, stirred for 1 hour and filtered. The collected solid was washed with diisopropylether and dried under vacuum to furnish 46.2 g of compound (IV) (46.2 g, 0.075 mol, 94% yield) of high chemical purity based on HPLC analysis (>99.0%).
Example 2
Synthesis of Miglustat Hydrochloride of Formula (III)
A solution of 2, 3, 4, 6-tetra-O-benzyl-N-butyl-1-deoxynojirimycin hydrochloride (VI) (100 g, 0.16 mol) in methanol (1000 mL), 10% HCl solution in methanol (100 mL), and 10% Pd/C (50% wet) (10 g) were mixed and stirred under hydrogen atmosphere at a temperature of about C. to about C. until completion of the reaction. The reaction mass was filtered and the solvent was removed from the filtrate by rotary evaporation. Ethyl acetate (1000 mL) was added to the residue from the rotary evaporation to precipitate the solid. The solid was filtered and dried to isolate Miglustat hydrochloride (III) (42 g, 0.16 mol, 100% yield) of >99.5% purity as measured by HPLC analysis. The DSC thermogram of this product is provided as FIG. 3, and the FTIR spectrum of this product is provided as FIG. 4.
Example 3
Synthesis of Miglustat of Formula (I)
Miglustat hydrochloride (III) (42 g, 0.16 mol) obtained from Example 2 was dissolved in 420 mL of methanol and DBU (1,8-diazabicycloundec-7-ene) (34.1 mL) was added. The reaction mass was warmed slightly and stirred for about 2 hours. The reaction was concentrated by removal of methanol. Dichloromethane (900 mL) was added to the residue. The resulting solid was filtered and dried to obtain crystalline miglustat (I) (27 g, 0.12 mol, 75% yield) of >99.5% purity as measured by HPLC analysis. The melting point of the crystalline miglustat (I) is C. The DSC thermogram and FTIR spectrum of the product are provided as FIG. 1 and FIG. 2, respectively. The crystalline miglustat (I) contained <0.05% of the 5R isomer (IV) as measured by HPLC.

Saturday, 25 June 2016

Billion-Dollar Products Coming Off Patent in 2016

2016 Patent Expirations.



JAPAN 2016




Vfend (Voriconazole) IN UK

According to a report by DCAT, based on IMS analysis, the following are some of the key patent expiries between 2014 and 2018.
  1. Nexium (esomeprazole): This patent expired in May 2014. Innovator AstraZeneca granted a license to Teva (TEVA) to produce the generic form in the United States.
  2. Celebrex (celecoxib): This patent expired in 2014. Pfizer conceded the drug to generic drug makers Actavis (ACT) and Teva after a prolonged lawsuit.
  3. Symbicort (budesonide/formoterol fumarate dihydrate): Some of AstraZeneca’s 13 patents have expired, but all won’t expire until 2023. No generic version of the drug exists.
  4. Crestor (rosuvastatin): AstraZeneca will lose its patent protection for Crestor in 2016.
  5. Cialis (tadalafi): Eli Lilly (LLY) is set to lose patent protection in the United States and Europe in 2017.



Ranking (by highest sales forecasts for 2020)

Pharmaceutical Company
2020 Forecast Sales (US $ billions)
Obeticholic acid
Chronic liver diseases, primarily primary biliary cirrhosis
Intercept Pharmaceuticals and Sumitomo Dainippon Pharma
Emtricitabine + tenofovir alafenamide (F/TAF)
HIV-1 infection
Gilead Sciences and Japan Tobacco
Tenofovir alafenamide + emtricitabine + rilpivirine (R/F/TAF)
HIV-1 infection
Gilead Sciences and Janssen R&D
MK-5172A (grazoprevir + elbasvir)
HCV infection
Merck & Co
Chronic lymphocytic leukemia
Nuplazid (pimavanserin)
Parkinson's disease psychosis 
ACADIA Pharmaceuticals
Uptravi (selexipag)
Pulmonary arterial hypertension
Nippon Shinyaku Co and Actelion

Analysis based on data accessed on January 08, 2016.
(SOURCE: Thomson Reuters Cortellis)


Obeticholic acid

Obeticholic acid.svg



 3 Venetoclax





New Blockbuster Drugs to Watch in 2016

Each of these new drugs could rake in $2 billion in sales.

Blockbuster drugs, those medicines that bring in more than $1 billion in sales every year, are the holy grail of drug development. They can make a pharmaceutical company and send them to rock-star status among investors, as evidenced by the rise of Gilead Sciences after the launch of its hepatitis C treatments. This year’s slate of new drug launches features at least seven drugs expected to hit blockbuster status within the next five years, according to a study by Thomson Reuters.
The line-up also reveals key trends within the pharmaceutical industry for this year and beyond, including an increasing focus on rare diseases, the development of more convenient single-dose regimens, and more affordable treatments.

Here are the seven drugs set to launch this year and reach blockbuster status by 2020.

1. Intercept Pharmaceuticals and Sumitomo Dainippon Pharma
Drug: Obeticholic acid
Indication: Chronic liver diseases, primarily primary biliary cirrhosis
2020 Forecast Sales: $2.62 billion
Intercept Pharmaceuticals’ ICPT -7.35% obeticholic acid has proved very effective in treating non-alcoholic steatohepatitis, a type of liver inflammation caused by fat build-up in the organ. This condition has no approved treatment and a potentially large market, which is expected to push the drug to blockbuster status, if approved. About 2% to 3% of the global population has non-alcholoic steatohepatitis and the share will likely increase due to rising rates of pre-disposing factors like obesity and insulin resistance.

2. Gilead Sciences and Japan Tobacco
Drug: Emtricitabine and tenofovir alafenamide (F/TAF)
Indication: HIV-1 infection
2020 Forecast Sales: $2 billion
Gilead’s GILD -3.48% two HIV-1 infection drugs in development are both expected to be big money-makers, and the company is hoping the new daily single-dosage options will be able to replace sales of its existing HIV treatments that are set to lose patent protections in 2017. The new TAF-based therapies show evidence that they are potentially a safer replacement for some current therapies, including Gilead’s own Truvada.

3. Gilead Sciences and Janssen R&D
Drug: Tenofovir alafenamide and emtricitabine and rilpivirine (R/F/TAF)
Indication: HIV-1 infection
2020 Forecast Sales: $1.57 billion
Like the No. 2 drug on this list, Gilead’s secondary TAF-based combination therapy in partnership with Johnson & Johnson’s JNJ -1.49% Janssen unit is expected to improve renal and bone mineral density measurements compared with some existing drugs. Those results combined with the improved longevity of HIV patients and increasing numbers of those eligible for antiretroviral drugs means a large and lucrative market for the two new TAF-based drugs.
 Tenofovir alafenamide structure.svg
Tenofovir alafenamide

4. Merck & Co.
Drug: MK-5172A
Indication: Hepatitis C virus
2020 Forecast Sales: $1.54 billion
Merck MRK -3.12% is getting ready to enter the heated market for hepatitis C treatments, going up against Gilead’s Harvoni and Abbvie’s Viekira Pak. Following a significant setback when theFood and Drug Administration withdrew its “breakthrough drug” status, Merck’s treatment could finally launch this year to give another safe and high-quality treatment for the disease. A recent warning by the FDA concerning Viekira Pak has dampened sales of Abbvie’s drug, which could give Merck a leg up when it eventually brings its hepatitis C drug to market. It could also pursue an aggressive pricing strategy to gain market share, given the currently high price tags on current treatments.

5. Abbvie
Drug: Venetoclax
Indication: Chronic lymphocytic leukemia
2020 Forecast Sales: $1.48 billion
Abbvie’s ABBV -2.37% Venetoclax is a potential oral treatment for cancer, primarily focused on a type of chronic lymphocytic leukemia that is resistant to chemotherapy. The drug was a leading therapy at last year’s annual meeting of the American Society of Hematology after a clinical trial showed an overall response rate of 79.4% in patients with relapsed chronic lymphocytic leukemia. The drug is also being tested as a potential treatment for other hematological cancers like non-Hodgkin’s lymphoma, as well as in combination with tamoxifen in patients with metastatic breast cancer.

6. ACADIA Pharmaceuticals
Drug: Nuplazid
Indication: Parkinson’s disease psychosis
2020 Forecast Sales: $1.41 billion
ACADIA’s ACAD -6.18% nuplazid could be the first and only drug on the market to help treat Parkinson’s disease psychosis, which affects up to 40% of Parkinson’s patients. Clinical trials have shown that the drug does not worsen motor symptoms, a vital factor for these patients, while improving night-time sleep, daytime wakefulness, and caregiver burden. Nuplazid may also work in other psychosis settings, such as schizophrenia and Alzheimer’s disease psychosis. The combination of those three diseases means ACADIA’s drug has a potentially massive and therefore lucrative market.

7. Nippon Shinyaku and Actelion
Drug: Uptravi

Indication: Pulmonary arterial hypertension
2020 Forecast Sales: $1.27 billion
Nippon Shinyaky’s Uptravi is able to both delay the progression of pulmonary arterial hypertension, a type of high blood pressure that affects arteries in the lungs and heart, as well as reduce the risk of hospitalization. The drug is the only one on this list that’s already available. It entered the market in the first week of January 2016 and is expected to bring in $189 million in its first year, with sales increasing to $1.27 billion by 2020. Uptravi is being promoted as an additional therapy once baseline treatment has been started. A massive clinical trial showed that Uptravi reduced the risk of death from pulmonary arterial hypertension by 39% versus placebo.

  1. Opdivo, Bristol-Myers Squibb, $5.684 billion
  2. Praluent, Regeneron Pharmaceuticals and Sanofi, $4.414 billion
  3. LCZ-696, Novartis, $3.731 billion
  4. Ibrance, Pfizer, $2.756 billion
  5. Iumacaftor plus ivacaftor, Vertex Pharmaceuticals, $2.737 billion
  6. Viekira Pak, AbbieVie, $2.500 billion
  7. Evolocumab, Amgen and Astellas Pharma, $1.862 billion
  8. Gardasil 9, Merck & Co., $1.637 billion
  9. Brexpiprazole, Ostuka Pharmaceutical and Lundbeck, $1.353 billion
  10. Toujeo, Sanofi, $1.265 billion
  11. Cosentyx, Novartis, $1.082 billion





 The pharmaceuticals losing patent protection in 2016

 The pharmaceuticals losing patent protection in 2016

A review of the drugs to watch in 2016 identifies several key areas of continued focus in the pharmaceutical industry: rare diseases, FDC regimens and pricing. The year ahead is anticipated to be a very interesting, and challenging, one for the pharmaceutical industry.


Billion-Dollar Products Coming Off Patent in 2016

2016 Patent Expirations
- See more at:

Billion-Dollar Products Coming Off Patent in 2016

2016 Patent Expirations
- See more at: