API and IP Newsletter
Contents
Recent FDA approvals: Fexinidazole
Fexinidazole was approved for medical use in the United States in July 2021.
Fexinidazole was first described in 1978. It was given a positive opinion by the European Medicines Agency in 2018. The development for sleeping sickness was funded by the Drugs for Neglected Diseases initiative in collaboration with Sanofi.
Sleeping sickness is a parasitic disease transmitted by the bite of an infected tse-tse fly. It affects mostly populations living in remote rural areas of sub-Saharan Africa, where about 65 million people are at risk of infection. Left untreated, sleeping sickness is always fatal.
WO2014079497A1 issued to Sanofi claims process of manufacturing of Fexinidazole. The API is synthesized by
Reacting 1-methyl-2-hydroxymethyl-5-nitro-imidazole with methane sulfonyl chloride in the presence of a suspension of powdered alkaline carbonate in an anhydrous organic solvent.
Adding to the resulting reaction medium, a solution of 4-methylmercapto-phenol in the organic solvent
No OB listed patents yet.
NCE-1 date 16 July 2025
It appears simple chemistry, of course there could be few challenges of dimer formations and those to be addressed. All metronidazole suppliers should able to manufacture Fexinidazole.
There are no DMFs filed so far, but if there is market in US, one could see many DMFs soon.
General information
Revealed: the pharma companies best equipped with AI
While there has been increasing interest in AI in the pharma space, there are still untapped opportunities in using AI in clinical trials specifically. Most large AI companies with name recognition like DeepMind Technologies and Exscientia are relatively driven more by molecule optimisation, drug repurposing, or drug discovery compared with AI use in clinical development
News here.
GSK’s top scientist to quit, become CEO of anti-ageing start-up
After just four years as GSK’s R&D chief, Hal Barron is leaving the pharma giant to head up Altos Labs, a biotech that aims to reverse disease through cellular rejuvenation programming.
News here.
Intellectual Property
Delaware Court held Hikma generic icosapent ethyl does not infringe patents underlying Amarin Pharma’s drug Vascepa
The active ingredient in Amarin’s Vascepa product is icosapent ethyl, an ethyl ester of an omega-3 fatty acid (EPA) commonly found in fish oils.
Vascepa currently has two FDA-approved indications: (1) treatment of severe hypertriglyceridemia (the “SH indication”); and (2) cardiovascular risk reduction (the “CV indication”).
After receiving FDA approval to market Vascepa for the SH indication, Amarin conducted further clinical studies to examine the effects of Vascepa on cardiovascular risk reduction.
Based on the results of the study, the FDA approved Vascepa in December 2019 for the CV indication. Amarin was permitted to add the CV indication to the Vascepa label and remove the CV limitation of use.
The ʼ537 patent was issued on 11 July 2017 and is assigned to Mochida, relates to CV, Amarin has an exclusive license.
The ’861 patent was issued on 25 February 2020. It is assigned to Amarin. Claim 1 of `861 describes a method of reducing the risk of cardiovascular death in a patient with established cardiovascular disease by administering icosapent ethyl.
On 5 November 2020, Hikma launched a generic version of Vascepa after receiving FDA approval of its ANDA.
Hikma’s ANDA contained a so-called “section viii- label carve out” regarding the asserted patents viz `537 and `861.
When Hikma originally submitted its ANDA in 2016, it only sought approval for the SH indication, as the FDA had not yet approved Vascepa for the CV indication.
At that time, Hikma’s proposed generic label (like the Vascepa label at that time) referred only to the SH indication and contained the CV limitation of use.
After Amarin received approval for the CV indication and listed the asserted patents in the Orange Book, Hikma submitted ‘section viii’ statements with respect to those patents.
Hikma did not propose to add the CV indication to its label, but Hikma did remove the CV limitation of use from its proposed label.
The FDA approved Hikma’s ANDA on 21 May 2020.
By the time Hikma’s product hit the market in November 2020, most doctors who prescribed Vascepa did so for uses other than the SH indication, and Hikma was aware of that fact.
Hikma issued press releases in 2020 regarding its generic product. In a 31 March 2020 press release, Hikma referred to its then-unapproved product as a generic version of Amarin Corporation’s Vascepa® 1 gm (icosapent ethyl) capsules.
The press release further stated the prior year’s “US sales of Vascepa® were approximately $919 million. The Vascepa sales figure cited by Hikma in the press release included sales for the CV indication.
Hikma’s website also advertised its generic version as being “AB” rated in the Therapeutic Category: Hypertriglyceridemia
The webpage of Hikma does not refer to the fact that Hikma’s product is only FDA-approved for SH.
According to the Complaint of Amarin, Hikma’s label, press releases, and website “instruct, promote, and encourage” healthcare providers and patients to administer Hikma’s product in a way that infringes the asserted patents.
Health Net is a health insurance provider. Vascepa is covered by Health Net’s insurance plans and appears on Health Net’s formularies as a covered drug. When Hikma launched its generic version, Health Net added the generic to its formularies, meaning that it would provide insurance coverage and/or payment for Hikma’s product.
Some of Health Net’s formularies currently list Hikma’s generic version as a Tier 1 drug and Vascepa as a Tier 3 drug. The result is that plan beneficiaries have to pay a higher copay for Vascepa than they do for Hikma’s generic version. Heath Net is another defendant. This article does not cover Court’s view as regards to Health Net. We will confine only to skinny label discussions as regards to defendant Hikma.
GSK is the landmark decision by CAFC in the recent past in view of skinny labels.
The Court held that GSK is a "narrow, case-specific review" and that it is still the law that "generics could not be held liable for merely marketing and selling under a 'skinny' label omitting all patented indications
An "AB rating," as the complaint explains, reflects that a generic drug is therapeutically equivalent to a branded drug. In GSK case it was held that where a generic label does not effectively carve out a patented use, advertisement that the drug is "AB rated" can support a finding of inducement.
Arnarin contends that Hikma's label teaches CV risk reduction for two reasons. First, Hikma's label contains a notice regarding side effects for patients with CV disease. Second, Hikma's label does not state that Hikma's 'generic version' of VASCEPA should not be used for the CV Indication
Hikma responded that (1) the notice regarding side effects is a warning and thus not an instruction to use icosapent ethyl to reduce cardiovascular risk, and (2) the removal of the CV risk reduction limitation is mere silence and that Hikma has no duty to discourage infringing use.
The Court had to decide since Hikma’s label does not instruct CV risk reduction, whether Hikma' s public statements, including press releases and Hikma' s website, would induce the infringement?
The Court said, Hikma' s press releases might be relevant to intent but they do not support actual inducement. Hikma's advertising of icosapent ethyl as the "generic equivalent" of Vascepa does not expose Hikma to liability.
The Court said, the intent alone is not enough; Amarin must plead an inducing act.
Amarin argued that Hikma's website induces infringement by advertising its product in the therapeutic category "hypertriglyceridemia." Amarin said, hypertriglyceridemia is broader than the Indications and usage sections of Hikma's Label, which includes only SH indication.
The question before the court was whether this is enough (ie without a label or other public statements instructing as to infringing use) to induce infringement. The Court found that it was not. This statement in press does not rise to the level of encouraging, recommending, or promoting taking Hikma's generic for the reduction of CV risk.
Decision here.
