Contents
Analysis development portfolio of Sun Pharma based on Import-Export Database!
We analysed import-export data of Sun Pharmaceuticals. This is a huge dataset and we have just scratched the surface and discovered few of the molecules which could be under development at various stages at Sun Pharma’s development center. This analysis is indicative and not exhaustive but could be very interesting.
Please find SIDVIM comments in the last column of the table. However, few general observations.
1. Molecules, even in early Phase III, have been selected for development.
2. There are many Chinese intermediate sources, however, in most of the cases there are more than one Chinese source being registered in the dossier. This would help to secure supply during commercial manufacturing.
3. Very varied development portfolio, not concentrating on any particular therapeutic category or type of compounds.
Intermediate name | QTY Kg | API | SIDVIM Comments |
4-Amino-3-chlorophenol hydrochloride | 61 | Alpelisib | Sun is very actively working on Alpelisib. FDA approval in May 2019, Sun had placed RM orders in tune of 60 Kgs, indicating that Sun must be in very advanced stages of development. Scinopharm and DRL are other two players active in Alpelisib. Even if there are only Chinese intermediate sources, Sun is securing supply by ordering RMs from multiple Chinese sources. |
| 10 | |
| 2 | |
4-Chloro-7-methoxyquinoline-6-carboxamide | 1.5 | |
| 1.5 | |
| 30 | |
| 31 | |
4-Fluoroaniline | 0.05 | |
9-(2-Phosphonomethoxypropyl)adenine | 0.6 | Apropovir | Apropovir is an interesting product. There is only one other DMF. More details to be found out here. The safety and efficacy of Apropovir have not been established in patients coinfected with HBV and HIV-1
|
| 0.6 | |
1,4-Cyclohexanedione monoethylene acetal | 60 | Atovaquone | An old approval, which was discontinued. New combination approval would have gone generic and Sun could be working on combination formulation. |
(5Z)-methyl 7-((1R,2R,3R,5S)-3,5-dihydroxy-2-((S,E)-3-hydroxy-5-phenylpent-1-enyl)cyclopentyl)hept-5-enolate | 0.5 | Bimatoprost | There are many other DMFs. Many ANDA filers, Sun would be one of those. |
| 0.3 | |
2-Methoxy-5-nitrophenol | 80 | Bosutinib | Five other DMF filers, Pfizer and Sun have settled their litigation in US and details are not available in public domain. But noticing quantities imported for API intermediates, Sun could be in advance stages of preparation of commercial supply. Prima facie commercial launch looks difficult before 2025 in US. |
(R)-4-Propyldihydrofuran-2(3H)-one | 75 | Brivaracetam | Seven DMFs are available. Sun could be in advance stages of API development. Generic launch would be litigation driven in USA. Launch could be possible in 2021 in Europe |
| 10 | |
| 1 | |
| 4 | |
1-(2-Fluoro-6-(trifluoromethyl)benzyl)-6-methylpyrimidine-2,4(1H,3H)-dione | 30 | Elagolix | FDA approval in 2018. NCE-1 date in July 2022. We analyzed the import data of many companies, and even though there is only one DMF by now, many companies are working on Elagolix! Sun is one of them. |
| 1 | |
| 1 | |
| 34 | |
| 35 | |
| 1.5 | |
| 1.5 | |
| 25 | |
| 25 | |
| 3 | |
| 3 | |
| 66 | |
| 0.01 | |
| 3 | |
2-Amino-3,5-dibromopyrazine | 0.45 | Entospletinib | Entospletinib is an experimental drug for the treatment of various types of cancers under development by Gilead Sciences. Very early selection by Sun! |
| 0.05 | |
| 0.5 | |
6-Bromo-3-hydroxypyrazine-2-carboxamide | 0.5 | Favipiravir | Favipiravir came into the limelight in Covid days. Like all other companies Sun is also working on it. Only DMF filed so far, but it is not a secret, many companies are active! |
| 0.37 | |
| 0.13 | |
| 0.5 | |
| 5 | |
| 1 | |
| 1 | |
| 7 | |
(7a,17b)-7-(9-((4,4,5,5,5-Pentafluoropentyl)thio)nonyl)-estra-1,3,5(10)-triene-3,17-diol 17-acetate | | Fulvestrant | Sun has not filed DMF yet, but 11 others have, Sun would be one of them! |
| 9.34 | |
| 1.18 | |
| 1.74 | |
| 10.4 | |
| 27.79 | |
1,2,3-Tri-O-acetyl-5-deoxy-beta-D-ribofuranose | 1.5 | Galocitabine | Molecules still seems to be in PIII trials. Sun is working on molecules under clinical studies. |
(2R 3R)-3-(2 5-DIFLUOROPHYENYL)-3-HYDROXY-2-METHYL-4-(1H-1 2 4-TRIAZOL-1-YL)THIOBUTYRAMIDE | 0.7 | Isavuconazole | Not many DMF filers. Specific salt patent is expiring in 2025. Generic launches possible in 2025. |
| 0.5 | |
6-Amidino-2-naphthol Methanesulfonate | 1 | Nafamostat | This drug has been identified as a potential therapy for Covid. with clinical trials in Japan and Korea. Sun would have started developing with a potential treatment for Covid. Eight known suppliers in databases. |
4-Guanidinobenzoic acid hydrochloride | 1.5 |
|
| 15 | |
| 1 | |
| 1 | |
| 10 | |
6-Amidino-2-naphthol Methanesulfonate | 1.5 | |
| 1 | |
| 1 | |
| 1.5 | |
| 5 | |
| 0.5 | |
| 16 | |
| 0.5 | |
| 0.5 | |
(S)-4-(3-((tert-butoxycarbonyl)amino)-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate | 0.01 | Netarsudil | December 2017 approval. Could be at early stage of development looking at quantities of intermediates being imported. |
| 0.02 | |
| 0.01 | |
| 0.01 | |
| 0.3 | |
4-(Hydroxymethyl)phenylacetic acid | 2.5 | |
| 1 | |
| 1.9 | |
Triisopropylsilyl chloride | 4 | |
2-Amino-5-nitrothiazole | 1 | Nitazoxanide | This is an old molecule, reconsidered as potential treatment for Covid and Sun Pharma must have developed interest. Looking at the ordered quantity, API development could be at early stage. |
5-Aminoimidazole-4-carboxamide | 80 | Dacarbazine | Very old drug. Not sure how this would have caught interest. Not many API suppliers. |
| 50 | |
| 25 | |
| 20 | |
2,2′-(Ethylenedioxy)diethanethiol | 25 | Plecanatide | 2017 approval, two DMFs already filed. Noticing intermediate ordered quantities, it seems all is set for NCE-1 filing for Sun! |
| 20 | |
1-(3-Methoxypropyl)-4-piperidinamine | 2 | Prucalopride | December 2018 FDA approval. NCE-1 date preparation? |
4-Amino-5-chloro-2,3-dihydrobenzofuran-7-carboxylic Acid | 2 | |
Methyl 4-hydroxy-7-phenoxyisoquinoline-3-carboxylate | 0.5 | Roxadustat | Approved in China in December 2018 for CKD. Not approved in other key markets. |
| 0.5 | |
1-(3-Ethyl-4-hydroxymethylphenyl)ethanone | 0.5 | Siponimod | Match 2019 approval. Sun is preparing for DMF/ANDA filing? As per public domain information, it seems 4-5 other companies including DRL, Teva, Virupaksha are also active in Siponimod. |
| 0.5 | |
4-Bromo-3-(trifluoromethyl)benzoic acid | 1 | |
| 1 | |
(S)-1-Phenyl-1 2 3 4-tetrahydroisoquinoline{(1s)-1-phenyl-1 - 2 3 4-tetrahydroisoquino} | 99.75 | Solifenacin | Very crowded market. Many Gxs have already launched. Sun would be one among them. |
| 0.25 | |
R-3 Quinuclidional (cas no: 25333-42-0) (batch: R3Q/0011218 etc) (chemical to make Solifenacin succinate (API) | 0.18 | |
4-Amino-3-hydroxybenzoic acid | 12 | Tafamidis | May 2019 approval. Sun seems to be very active. NCE-1 date preparation? |
| 12 | |
| 3 | |
| 3 | |
4-Bromo-3-fluoro phenol | 5 | Tedizolid | This is 2014 approval. Generic launch could be challenging prior to 2028 in US. No DMFs reported yet. Commercial aspects to be checked, peak sales estimated was about $ 300 million. This could become a niche molecule. |
| 25 | |
| 21 | |
| 9 | |
(2 2-Difluoro-1 3-benzodioxol-5-yl)acetonitrile | 1.5 | Tezacaftor | 2018 approval, Scinopharm, another API company, is active in this API. Perhaps Sun is preparing for NCE-1 filing? |
2-bromo-5-fluoro-4-nitro aniline | 2 | |
(1R 2S)-REL-2-(3 4-difluorophenyl) cyclopropanamine hydrochloride | 7 | Ticagrelor | Very crowded market, more than 25 DMFs available, Sun to compete in this space. Ticagrelor would become future Clopidogrel. |
| 0.02 | |
2-((3aR,4S,6R,6aS)-6-amino-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yloxy)ethanol L-tataric acid | 15 | |
4 6-Dichloro-2-(propylsulfanyl)pyrimidin-5-amine | 10 | |
| 98 | |
| 20 | |
| 92.14 | |
| 84.51 | |
4-(Trifluoromethoxy) phenyl boronic acid | 68 | Sonidegib | 2015 approval. Looking at the ordered API quantities Sun must be at late stage of development. MSN had already filed DMF, Sun could follow soon? |
| 45 | |
| 1 | |
7-Chloro-1 2 3 4-tetrahydro-5H-1-benzazepin-5-one | 6 | Tolvaptan | Twelve other DMF filers. Sun would be one of those! |
(3R 4S)-3-(2-Bromoacetyl)-4-ethyl-1-pyrrolidinecarboxylic acid phenylmethyl ester | 0.5 | Upadacitinib | 2019 approval. 5 other players are already active. It seems Upadacitinib is going to be very competitive for Gxs on day-1. |
| 0.5 | |
N-[5-[(4-Methylphenyl)sulfonyl]-5H-pyrrolo[2 3-b]pyrazin-2-yl]carbamic acid ethyl ester | 0.1 | |
(1S 2S 3R 5S)-(+)-2 3-Pinanediol | 4 | Vaborbactam | Combination with Meropenem approved 2017. Sun is preparing for NCE date? If this combination does well in the market, there would be good days for Meropenem too. |
| 2 | |
N-[(2 -cyanobiphenyl-4-yl)methyl]-l-valine methyl ester hcl{ - cyanobiphenyl valine ester hydrochloride} | 6.15 | Valsartan | Old product |
(5R)-5-(2 2-dimethyl-4H-1 3-benzodioxin-6-yl)-1 3-oxazolidin-2-one | 0.35 | Vilanterol | Combination with Fluticasone approved in September 2017. Sun is eyeing on exclusivity expiration date? |
| 1.6 | |
| 0.15 | |
| 0.15 | |
2-[2-(6-Bromohexyloxy) ethoxymethyl]-1,3-dichlorobenzene | 0.1 | |
| 0.5 | |
| 2.7 | |
| 0.7 | |
| 0.1 | |
| 0.5 | |
General information
EDQM releases updated pharmacopoeial quality standards for vaccines
The European Directorate for the Quality of Medicines & Healthcare (EDQM) has released an updated set of pharmacopoeial quality standards for vaccines, with the aim to help those developing COVID-19 vaccines.
Originally published in June 2020, the EDQM says that the package now includes a further 17 texts on analytical methods which are referenced in the recently released EDQM document on recombinant viral vectored vaccines for human use. (Read more)
Select patented drugs to be included in India's NLEM?
An intense debate is going on in India on whether patented drugs should be selected and identified for inclusion in the National List of Essential Medicines (NLEM) 2020, which is being finalized by the Expert Committee constituted by the Ministry of Health. The increasing burden of cancer and rare diseases, as well as the high cure rate now being achieved by patented drugs especially in the treatment of cancer, are adding to the claim for inclusion. (Read more)
Intellectual Property
Epinephrine Solution CAFC decision on 23 November 2020
Market size:
According to IQVIA™, U.S market annual sales for the 12 months ended December 31, 2019 for Epinephrine Injection, 30mg/30mL (1mg/mL) Multiple Dose Vial was approximately $ 131 million.
Orange book Patents
Product No | Patent No | Patent Expiration | Drug Substance | Drug Product | Patent Use Code | Submission Date |
001 | 9119876 | 03/13/2035 |
| DP |
| 09/01/2015 |
001 | 9295657 | 03/13/2035 |
|
| U-1829 | 04/12/2016 |
001 | 10130592 | 03/13/2035 |
| DP |
| 11/26/2018 |
Background of the case:
OB listed patents of Par US 9,119,876 and US 9,295,657, claim compositions containing Epinephrine. Hospira filed ANDA. Par sued Hospira for patent infringement. District court opined in favour of Par & held that Hospira’s ANDA infringing certain limitations of asserted claims. Matter was in appeal and last week appeal Court, Federal Circuit (CAFC) affirmed District Court & held that Hospira’s ANDA infringes composition limitations.
The representative claim 1 of the ’876 patent is as follows.
A composition comprising:
1. in the range of about 0.5 to 1.5 mg/mL of epinephrine and/or salts thereof,
2. in the range of about 6 to 8 mg/mL of a tonicity regulating agent,
3. in the range of about 2.8 to 3.8 mg/mL of a pH raising agent,
4. in the range of about 0.1 to 1.1 mg/mL of an antioxidant,
5. in the range of about 0.001 to 0.010 mL/mL of a pH lowering agent, and
6. in the range of about 0.01 to 0.4 mg/mL of a transition metal complexing agent, wherein the antioxidant comprises sodium bisulphite and/or sodium metabisulfite.
It is important to note highlighted text in the part of the claim represented above. Those limitations have been contested viz. issues related to limitations of tonicity agent, pH lowering agent & transition metal complexing agent.
A decision of CAFC: -
1.) “about 6 to 8 mg/mL of a tonicity regulating agent” limitation
Hospira argued that its ANDA contains concentration of 9 mg/mL of sodium chloride & thus falls outside of the claim scope. However, the court attributed Dr. Elder’s testimony, which focused on the technological facts, Dr. Elder explained the purpose of both ends of the claim range, he explained why it was clear that a “physiologically acceptable” concentration would include
concentrations as high as 9 mg/mL. The court agreed to Dr. Elder’s view and opined 9 mg/mL is part of the claimed range even if the claimed range is “about 6 to 8 mg/mL”.
2.) “about 0.01 to 0.4 mg/mL of a transition metal complexing agent” limitation
Hospira argued that the analysis should focused entirely on the characteristics of the composition that Hospira was likely to sell, not on what compositions the ANDA, and the Court (CAFC) said, sorry, it is the ANDA that governs infringement analysis & not the product which would be sold.
3.) “about 0.001 to 0.010 mL/mL of a pH lowering agent” limitation
Hospira allegedly used citric acid as a buffer. Hospira argued the District Court improperly considered citric acid as a pH lowering agent. Federal circuit rejected Hospira’s argument.
Detailed case reported here.
Disclaimer
Sidvim LifeSciences Private Ltd has taken due care and caution in
developing this document. Since the data used for analysis in this document is
based on the information available in the public domain, its adequacy or
accuracy or completeness cannot be guaranteed. This document is for information
only and Sidvim is not responsible for losses that may or may not arise due to
any decisions made based on the same. No part of the document shall constitute
or be represented as a legal opinion of any kind or nature. No warranties or
guarantees, expressed or implied, are included in or intended by the document,
except that it has been prepared in accordance with the current generally
accepted practices and standards consistent with the level of care and skill
exercised under similar circumstances by professional consultants or firms that
perform the same or similar services.
