Sandoz Files 351(k) Application for Adalimumab Biosimilar

Sandoz announced that it has thrown its hat in the ring for another Humira biosimilar. Sandoz filed an European application for approval for GP2017 last year, in the expectation that it will be able to launch soon after the European patent expires in October 2018.

This will be the third application for an adalimumab biosimilar. Versions by Amgen (Amjevita) and Boehringer Ingelheim (Cyltezo) have been approved by the Food and Drug Administration (FDA); however, patent litigation has held up marketing. Amgen had signed an agreement with Humira’s manufacturer Abbvie to postpone marketing until 2023. Boehringer Ingelheim has not signed a similar agreement, but no indication is yet given regarding the US launch of this product.

It is assumed that European revenues will sustain the biosimilar manufacturers until US marketing begins. This is Sandoz’s fifth FDA biosimilar application. It has received approval for Zarxio (filgrastim) and Erelzi (etanercept); its application for rituximab is under review, and it received a rejection for its version of pegfilgrastim.

A Profile on Lesser-Known Player in the Biosimilar Space: Lupin Pharmaceuticals

On occasion, we profile some biosimilar manufacturers about whom our readers may not be as familiar as the large players like Sandoz, Amgen, and Pfizer. This generally refers to companies that have products that are in earlier-stage research or those who simply have not been in the news as often as their colleagues. In this post, we highlight a Baltimore-based company, Lupin Pharmaceuticals.

Lupin is a subsidiary of the Indian company Lupin Limited. It is perhaps best known as a manufacturer of generic drugs, especially anti-infectives.

Why you may be hearing more about this company: At a January JP Morgan investor conference, Lupin announced its intention to bring a biosimilar application for etanercept to the European Medicines Agency in early 2019, with a 351(k) application filed with the Food and Drug Administration the following year. Additionally, Lupin has indicated that it will be jumping into the biosimilar market with both feet, with early-stage development beginning for six other medications: aflibercept, denosumab, filgrastim, pertuzumab, pegfilgrastim, and ranibizumab. It believes that the combined global market for these agents is $24 billion.

Lupin has not announced any marketing partnerships, meaning that they may decide to go it alone, unlike some of the major players (e.g., Allergan–Amgen, Celltrion–Pfizer, Samsung Bioepis–Merck, etc). With its extensive generic portfolio, Lupin may believe that it has the sales force necessary to effectively market in the biosimilar space as well.

In other news…Novartis has announced an unusual clinical trial move. In its clinical trial program for secukinumab (Costentyx®), it has engaged in a head-to-head trial against both Humira® and its own (i.e., Sandoz’s) biosimilar version of adalimumab (GP2017).  The head-to-head trial with GP2017 focuses on the ankylosing spondylitis indication, whereas the Humira comparative-effectiveness trial involves patients with psoriatic arthritis.

The Coming Adalimumab Biosimilar Pricing Free-for-All

The dam wall will be broken when AbbVie’s patents on Humira® are invalidated or expired, or perhaps litigation is settled. This may happen in 2018, 2020, 2022—it is really anyone’s guess, but the one thing that is known for sure is that the day after this occurs, a quite sudden experiment in intensive competition will be underway.

There will be anywhere from 3 to 5 adalimumab biosimilars approved by the FDA when the patent fight is done. Unlike in the Hatch-Waxman Act, where there is an exclusivity period for the first generic market entrant, the BPCIA does not grant a similar benefit for the first-to-market biosimilars. And by the year 2018 or 2020, most expect the 180-day notification period to either be nullified by the Supreme Court or by Congressional legislation. In other words, there will be little restraint on competition.

Manufacturer Product Comments
Amjevita™ (adalimumab-atto)
Approved by the FDA in September 2016
Amgen believes launch in 2017 is unlikely due to patent issues
Boehringer Ingelheim
BI 695501
Filed for approval with FDA and EMA in January 2017; approval decision in Q4 2017
FDA application delayed from Q4 2016 due to manufacturing capacity issues
Phase 3 trial’s top line results reported, FDA application expected in 2017
Coherus Bioscience
Phase 3 trial’s top line results reported, FDA application expected in 2017
Samsung Bioepis
Filed with EMA in July 2016
The Merck Group (EMD Serono)
Phase 3 trials underway for plaque psoriasis (may only target this indication)

Will AbbVie remain in what is still a highly lucrative market for a drug that has paid off its research and development investment many times over? It is likely that with all of the potential players trying to keep their heads above water during the flood of competition, pricing discounts could finally be close to the dreams of payers and other purchasers (≥ 40%). This scenario depends somewhat on whether one player gambles on an early start and markets their product before patent litigation is cleared. This launch “at risk” could alter the competitive landscape. Another possible element could be AbbVie entering into an agreement with Amgen, allowing it to launch well before the others are approved. However, AbbVie’s pronouncements to date seem to be focused on fortifying the dam wall not breaching it.

The only parallel may be the moment the 6-month generic exclusivity expires, and a gaggle of manufacturers launch their products. However, we’re on a completely different level of expenditure and potential savings here. Hopefully, the dam breaks sooner than later.