3 March 2015Americas

Exclusivity: Close to the edge

During this year the beginning of the end of the so-called patent cliff for small molecules will come, as the number of blockbuster drug patent expiries starts to tail off. Two of the biggest selling drugs in the US—Abilify (aripiprazole) and Lantus (insulin glargine)—are among those that will lose patent protection there this year, compared with three that slipped off the cliff last year, according to IMS Health figures.

The small molecules cliff will soon make way for the biologics cliff—a phenomenon that is predicted to come into effect around 2020—but before then, here are five drugs that will lose US patent protection this year, possibly having a major impact on their makers.

Gleevec (imatinib)

Patent expired on January 4

Gleevec (known as Glivec in the EU, Australia and Latin America) has been hailed as something of a miracle drug, helping to nearly double the rate of people with chronic myeloid leukaemia (CML) who survive at least five years. Approved by the US Food and Drug Administration (FDA) in 2001, the drug has helped that survival rate increase from 31% in 1993 to 59% for those diagnosed between 2003 and 2009.

So important was the drug for public health in India that in 2013 Gleevec’s maker Novartis was refused a patent protecting the drug in the country despite its having equivalent patents in many other countries.

Gleevec is Novartis’s biggest selling product by far, generating $4.7 billion worldwide in 2014, almost twice as much as the company’s second best-seller, multiple sclerosis treatment Gilenya (fingolimod).

The main US patent covering the drug expired on January 4 (paediatric exclusivity protects the drug until July 4), and with at least three companies vying to make a generic version, or already having a generic on the market, Novartis has been working hard to prepare itself for a big hit.

To compensate for potential lost profits, Novartis starting switching patients to another CML drug, Tasigna (nilotinib), the compound patent for which doesn’t expire until 2023.

Meanwhile, in Japan, Daiichi Sankyo has been marketing generic imatinib tablets, while Teva has received marketing authorisation from the European Medicines Agency (EMA) to make and sell generic versions of Gleevec.

In the US, Novartis settled patent litigation with Sun Pharma—with the terms of the settlement allowing Sun to launch a generic Gleevec in the US on February 1, 2016, despite the main patent’s expiry in January this year.

Lantus (insulin glargine [rDNA origin] injection)

Patent expired on February 12

Lantus (insulin glargine [rDNA origin] injection) is Sanofi’s best-performing medicine, not just in its diabetes portfolio, but across the board. Along with its partner product—the Lantus SoloStar pen—Lantus made $7.1 billion of Sanofi’s total $38.2 billion net sales worldwide in 2014, representing more than 18% of the company’s takings.

Last year’s 11% growth of Sanofi’s diabetes division in the fourth quarter was driven by Lantus, the company said. This is an important drug for Sanofi.

However, the France-based company has a strategy in place to help prop up its diabetes division after Lantus’s US expiry in February. Last August, Sanofi bought the rights to Mannkind Corporation’s Afrezza, an inhalable form of insulin. Afrezza, which was profiled in LSIPR’s March 2013 newsletter, launched in the US in February 2015, just in time for Lantus’s expiry.

Sanofi has also been developing a new diabetes product—Toujeo (insulin glargine), which is similar to Lantus. It is being reviewed by the FDA. If accepted, Toujeo will launch in the US in the first half of 2015.

In a statement last November, Sanofi said it expected its diabetes sales in the next four years to be fairly flat, assuming “substantial conversion” of patients from Lantus to Toujeo.

Some of the big pharma are poised to launch their own versions of Lantus. Eli Lilly and Boehringer Ingelheim have together developed their own insulin glargine injection, called Basaglar, which received marketing authorisation from the EMA last September, and has been granted tentative approval by the FDA.

Merck and Samsung Bioepis are also working together to develop a version of Lantus.

Namenda (memantine)

Patent expires on April 11

Actavis has a lot at stake with its Alzheimer’s drug Namenda, which it acquired after merging with Forest Laboratories last July. According to IMS Health, Namenda made worldwide sales of $1.7 billion in the 12 months ending June 30, 2014.

The main US patent covering the drug expires on April 11, although paediatric exclusivity remains until October 11. The terms of certain Forest settlement agreements allow some generic companies to launch versions of Namenda three months earlier than this date, in July.

Faced with possibly losing a sizable portion of its profits, Forest put a long-term strategy into effect last year. In February 2014, it announced that it would take Namenda off the market in August, and that it would sell the extended release formulation of Namenda—Namenda XR—exclusively. The main US patent covering Namenda XR expires in 2025.

However, Forest’s patient-switching strategy wasn’t looked upon favourably by New York state attorney general Eric Schneiderman, who, last September, filed an anti-competition lawsuit against Actavis. He argued that the company was “forcing” patients from the twice-a-day pill to the once-daily formulation of Namenda XR. The company was later barred from implementing its strategy.

Nevertheless, at an investor conference in January, Actavis chief executive Brett Saunders was quoted by the Wall Street Journal’s Pharmalot blog as saying that 40% of patients had made the switch and that the company has a “very good shot” at getting that number to 65% to 70% by the summer of 2015.

Actavis has another trick up its sleeve. In partnership with Californian pharma company Adamas, it has developed Namzaric, a fixed dose combination of Memantine XR and donepezil hydrochloride (the active ingredient in Pfizer’s Alzheimer’s drug Aricept, which lost patent protection in 2010). The FDA approved Namzaric last December.

Abilify (aripiprazole)

Patent expires on April 20

Bristol-Myers Squibb (BMS), which makes Abilify (aripiprazole), has a lot at stake with its depression drug. The product is New York-based BMS’s biggest seller, generating more than $2 billion in worldwide sales for the company last year, more than 12% of the company’s total sales of $15.9 billion.

Abilify’s total worldwide sales in the 12 months to June 2014 totalled $7.2 billion for BMS and Otsuka, which markets the drug with BMS, with the Japanese company claiming the bulk of the revenue. According to Otsuka, Abilify accounts for about 40% of its sales.

In an effort to bolster its central nervous system (CNS) portfolio before Abilify’s US expiry in April, Otsuka bought Californian pharma company Avanir last December. Avanir has a pipeline of pre-approved drugs to treat CNS conditions including Alzheimer’s disease, Parkinson’s disease and migraine.

Avanir’s flagship product Nuedexta (dextromethorphan hydrobromide), which treats pseudobulbar affect, also known as emotional incontinence—a condition characterised by involuntary bouts of laughter or crying—made $94 million in sales in the 12 months to June 30, 2014. Avanir’s compound patent on Nuedexta does not expire until 2023.

Also waiting in the wings is a ‘long-acting’ version of Abilify, called Abilify Maintena, which Otsuka developed with Danish pharma company Lundbeck. Maintena is a once-monthly injection of the medicine, which was approved by the FDA in February 2013.

Otsuka and Lundbeck are also lining up brexpiprazole which, like Abilify, treats schizophrenia and is an adjunctive therapy for major depression. The FDA accepted it for review last September.

Avodart (dutasteride) and Jalyn (dutasteride/tamsulosin)

Patent expires on November 20

GlaxoSmithKline’s (GSK) pill for an enlarged prostate is due to lose patent protection in the US in November. It has proved itself to be a strong performer for GSK: the Avodart franchise, which includes combination pill Jalyn, made $1.2 billion worldwide last year, 4% down on 2013.

The drug has undergone many challenges, however. In 2011, Watson (now Actavis) filed an Abbreviated New Drug Application with the FDA seeking approval to make and sell an Avodart generic.
GSK responded by suing Watson shortly after.

The main Avodart/Jalyn patent has also been targeted in the US by Banner Pharmacaps, Anchen, Roxane Laboratories and Mylan. In January 2013, GSK and Anchen settled their US-based litigation on terms that allowed Anchen to enter the Jalyn market in the fourth quarter of 2015, or earlier under certain circumstances.

GSK has also settled a challenge by Teva to Avodart, which means Teva can launch a generic version of Avodart in the US in late 2015 as well. Teva’s generic Avodart was FDA-approved in 2010.

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