API and IP Newsletter
Contents
ANDA approvals in July 2024
We follow ANDA approvals.
In July 2024, there were about 78 ANDA approvals. Among those, 12 were tentative approvals. The following Indian companies are at the top of the list and have sought approvals for more than 2 ANDAs.
Some of the other observations are as below.
General information
Gilead gets US FDA approval for inflammatory liver disease drug
The U.S. Food and Drug Administration on Wednesday approved Gilead Sciences’ liver disease treatment, Livdelzi, which it gained through a $4.3 billion buyout of CymaBay Therapeutics earlier this year.
News here
A Roadmap to Pharma Resilience
COVID-19 brought in enormous attention to Pharma resilience as the world faced a global pandemic and prepared for an unprecedented vaccine rollout across the world. But the importance of this topic is not limited to the pandemic. Climate changes, geopolitical tensions/wars, cyber-attacks, reputational damages, financial risks, currency risks, natural disasters, solar flares, and many unforeseen issues can cause massive supply chain network disruptions and impact the availability of life-saving drugs and critical therapies.
News here
Intellectual Property
Novartis Vs MSN
Novartis holds New Drug Application ("NDA") No. 207620 for Entresto (sacubitril/valsartan) tablets.
Entresto is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure, and for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older.
Several drugmakers, including Defendants MSN Pharmaceuticals Inc and others (collectively, "MSN"), have filed ANDAs seeking FDA approval to launch generic sacubitril/valsartan products.
On 24 October 2022, Novartis filed a complaint alleging infringement of US patent, US 11,096,918 (the '"918 patent") by MSN and several other defendants (MSN).
The '918 patent covers the amorphous solid form of a compound ("TVS") present in Entresto that is comprised of sacubitril, valsartan, and sodium cations. The patent expires on 8 November 2026.
Claim 1 of the '918 patent recites: 1. An amorphous solid form of a compound comprising anionic valsartan, anionic sacubitril, and sodium cations in a 1: 1 :3 molar ratio.
Following a Markman hearing, the Hon. Judge construed an amorphous solid form of a compound to mean "a solid form of a compound in which the amorphous form of the compound predominates. An amorphous solid form is mutually exclusive from a crystalline solid form, but not necessarily mutually exclusive from a partially crystalline solid form."
On 24 July 2024, MSN received final FDA approval for its ANDA product.
Novartis moves The District Court for The District of Delaware for a preliminary injunction to prevent the prospective at-risk launch of MSN's generic sacubitril/valsartan product.
Should its motion be denied, Novartis moves for a short stay to allow Novartis to seek injunctive relief from the Federal Circuit.
MSN also moves to strike portions of Dr. Matzer's (Novartis Expert witness) declaration, which was submitted by Novartis in support of its motion for preliminary injunction.
Novartis argued it is likely to succeed in showing that claim 1 of the '918 patent is valid and infringed by MSN's ANDA product.
MSN challenged Novartis's likelihood of success of proving infringement, but MSN did not raise any arguments regarding validity.
Novartis asserted that testing performed by its expert, Dr. Matzger, revealed that the drug substance in MSN' s product contains a small amount of amorphous TVS and does not contain crystalline TVS.
Novartis contended the drug substance in MSN's ANDA product, which MSN claims is a crystalline TVS complex and which the parties refer to as "Form-S," is a physical mixture of separate crystalline valsartan disodium and separate crystalline sacubitril sodium.
Novartis argued that the amorphous TVS compound therefore necessarily predominates over the (non-existent) crystalline TVS compound.
MSN argued that Novartis has not shown it is likely to succeed in proving MSN's product contains amorphous TVS.
Novartis's identification of amorphous TVS within MSN's ANDA product relies on Dr. Matzger's Raman mapping data. MSN noted that Dr. Matzger did not compare the spectra he obtained from MSN's API to Form-S reference spectra. MSN and its expert, Dr. Steed, argued that Dr. Matzger's test results were therefore based on incomplete data.
MSN asserted that, when the comparison is made between MSN's API spectra and the Form-S reference spectra, the peaks in MSN's API spectra that Dr. Matzger pointed to as proving the presence of amorphous TVS more closely match the peaks in MSN's Form-S reference spectra than those in amorphous reference spectra.
Novartis argued the criticism that Dr. Matzger did not use Form-S reference spectra is misplaced because Form-S is not in fact a crystalline TVS complex but a physical mixture of individual crystalline valsartan disodium and individual crystalline sacubitril sodium.
The Hon. Judge said even if he accepts Novartis's assertion as true, however, Dr. Steed's declaration still undermines Dr. Matzger's conclusions by supporting MSN's position that the amorphous regions Dr. Matzger identified are not actually amorphous TVS. The Hon. Judge found that Novartis had not met its burden of showing it is likely to succeed in proving MSN's ANDA products contain amorphous TVS.
Furthermore, the Judge found, Novartis had not shown it is likely to succeed in proving that Form-S is a physical mixture rather than a crystalline complex. MSN argued that XRPD, Raman, FT-IR, and DSC testing data submitted with its ANDA demonstrated that Form-S is not a physical mixture or amorphous.
Novartis challenged the ANDA testing as flawed because MSN never compared Form-S data to physical mixture data.
Novartis also contended that MSN's Raman data proved Form-S is a physical mixture. Novartis argued there are variations between the Raman spectra of the two samples of Form-S that would not be present if Form-S was a crystalline complex.
Novartis cites Dr. Matzger's Raman data in support of its position that Form-S was a physical mixture.
MSN argued that Dr. Matzger's Raman mapping does not show that MSN's API is a physical mixture or amorphous TVS, noting that MSN's Raman spectra from the two samples of Form-S contained different peaks from those that Dr. Matzger relied on to characterize the drug substance.
In the face of supporting test data and what appeared to be a valid criticism of said test data from both sides, the Judge said, he is unable to find that the record favors finding Form-S to be one of a physical mixture or a crystalline complex. He said, Novartis bears the burden of proof, both on infringement and on showing likelihood of success. He found Novartis had not met the burden it bears at this stage with regards to demonstrating that Form-S is a physical mixture.
For the reasons above, the Hon. Judge concluded Novartis had not shown it is likely to succeed on the merits of showing infringement of `918 patent.
Novartis's motion for preliminary injunction was denied. However, Novartis would appeal this decision and generics must wait, unless they decide to launch at risk. For such a block buster product, generally Gxs will not launch the product at risk and would wait for CAFC decision.
Decision here
