API and IP Newsletter
Contents
FDA approvals- Tovorafenib
We follow USFDA approvals for small molecules. We analyse Chemistry, IP and such other details.
On 23 April 2024, the USFDA granted accelerated approval to tovorafenib (Day One Biopharmaceuticals, Inc.) for patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation.
Low-grade gliomas are slow-growing tumors. As they grow, they press on surrounding healthy parts of the brain, affecting their function.
Tovorafenib, sold under the brand name Ojemda. For the market share Ojemda would compete Novartis’ Tafinlar-Mekinist combo. Based on the broad patient population and the lack of a boxed warning on the label, analysts at JPMorgan pegged Ojemda could reach around $750 million in peak sales. Here
Patent situation
WO2009006389 family claims compound and generic launch could be challenging before the expiration of compound patent. In US it is valid till 2031 and further extension could be possible. Tovorafenib, its preparation and its use in the treatment of Raf-mediated diseases is disclosed in this family.
Patent family WO 2013/144923 discloses methods for the treatment of non-BRAFV600E mutant melanoma in patients comprising administering a Raf inhibitor and a MEK inhibitor.
Example 3 of WO2018220533A2 describes optically Tovorafenib, teaches synthesis of 6-amino-5-chloro-N-((1R)-1-(5-((5-chloro-4-(trifluoromethyl)pyridin-2-yl)carbamoyl)-1,3-thiazol-2-yl)ethyl)pyrimidine-4-carboxamide ie Tovorafenib.
The crystallized substance isolated as a white powder, with optical purity 96.1% ee (chiral HPLC).(R)- Tovorafenib
WO2015148828 patent family claims pharmaceutical composition and would expire in 2035. The claim is as follows.
1. A pharmaceutical composition comprising:
(1) 10% to 50% w/w of a solid dispersion extrudate comprising:
(a) about 40% w/w of (R)- Tovorafenib, or a pharmaceutically acceptable salt thereof, and
(b) about 60% w/w of copovidone; and
(2) 90% to 50% w/w of one or more pharmaceutically acceptable excipients,
wherein the solid dispersion extrudate comprises <3% w/w of (S)- Tovorafenib.
There’s high likelihood that generic manufacturers who are eyeing to file ANDA on NCE-1 date would need to circumvent this composition patent claim.
NCE-1 date will be 23 April 2028.
Teva imported 2-Acetylthiazole-5-carboxylic acid in September and December 2023, much before approval of Tovorafenib. This is a starting material for Tovorafenib. Teva could be actively working in generic API and FDF development.
General information
Sandoz launches biosimilar Pyzchiva in Europe
Pyzchiva is approved for treatment of adults with plaque psoriasis, psoriatic arthritis, Crohn’s disease and in certain pediatric plaque psoriasis patients.
News here
Bayer Files NDA With U.S. FDA For Elinzanetant To Treat Moderate To Severe Menopausal Symptoms
Bayer said that a New Drug Application or NDA for the investigational compound elinzanetant has been submitted to the U.S. Food and Drug Administration (FDA) for the treatment of moderate to severe vasomotor symptoms (VMS, also known as hot flashes) associated with menopause
News here
Intellectual Property
Astellas Vs Ratiopharm (Mirabegron)
This case is about SPC of EP 1559427. The SPC was granted till December 2027. This could delay generic launches of mirabegron in Germany for the main indication.
The patent EP 1559427 claims
A remedy for use in the treatment of overactive bladder comprising mirabegron as an active ingredient.
Mirabegron is Astellas’ drug Betmiga. It is one of the company’s top-selling drugs.
Since this is a case related to the SPC of EP 1559427, let us understand first what is an SPC.
SPC is a supplementary protection certificate.
It comes into force after expiry of a patent upon which it is based. This is available for various regulated, biologically active agents, human or veterinary medicaments and plant protection products.
It normally has a maximum lifetime of 5 years. The duration of the SPC can, however, be extended to 5.5 years when the SPC relates to a human medicinal product for which data from clinical trials conducted in accordance with an agreed Paediatric Investigation Plan (PIP).
SPCs extend the monopoly period for a marketed product (active ingredient or a combination of active ingredients) that is protected by a patent.
However, though looks very straightforward, SPC sometimes becomes very complicated.
One must note, the SPC is granted if,
in the EU member state in which the SPC application is submitted
at the date of this SPC application, the product is protected by a basic patent in force,
a valid marketing authorisation (MA) has been granted, and
this MA is the first to place the product on the market as a medicinal product.
EP 1559427 had expired in November 2023 and in Germany (the EU member state) SPC was granted till December 2027.
The active ingredient mirabegron was previously considered for the treatment of diabetes mellitus, among other things. At the same time, it was already known that the substance class to which mirabegron belongs is also suitable for the treatment of urinary urgency and incontinence both symptoms of an overactive bladder.
In 2021, Ratiopharm filed a nullity action against the use patent and the SPC at the German Federal Patent Court on the grounds of lack of novelty. The court of first instance subsequently revoked the property rights in 2023 (case ID: 3 Ni 2/21 (EP)).
The Federal Patent Court was of the opinion that the novelty of the invention must result from the new use of an already known active ingredient. The judges found that this was not the case here, as documents already indicated that the class of substances was also suitable for urinary urgency and incontinence.
Astellas argued that the purpose of the basic patent was to find an improved therapy for overactive bladder and lodged an appeal.
The 2nd instance The Federal Court of Justice did not follow the reasoning of the first-instance court.
According to the judges of The Federal Court, there was no sufficient evidence from the state of the art that mirabegron is also suitable for treating an overactive bladder, despite the knowledge of the properties of the substance group.
The case ID: X ZR 92/23 is yet to be uploaded at the website. Though the details of the case would be in Deutsche, we could follow the reasoning of the judges of The Federal Court. As SPC is for the marketed product and granted MA is for mirabegron for overactive bladder and this could explain why Hon. Judge would have opined in favor of Astellas.
This could delay the generic launches of Mirabegron in Germany till 2027.
Decision here
