Dispute Over Pfizer's Inflectra And Data For Ardelyx's Tenapanor

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Includes: ARDX, AZN, JNJ, PFE
by: EP Vantage

Welcome to your weekly digest of approaching regulatory and clinical readouts. Patent litigation over Celltrion and Pfizer’s (NYSE:PFE) Inflectra, a biosimilar of Johnson & Johnson’s (NYSE:JNJ) arthritis antibody Remicade, will come to a head this month, and the case will have profound consequences for these and perhaps many other biosimilar makers.

And in the next month or two Ardelyx (NASDAQ:ARDX) will report phase III data on its lead project, tenapanor, in hyperphosphataemia. Since this caused unexpectedly high rates of diarrhea in phase II crashing the company's shares, investors will no doubt be watching closely.

Biosimilar fight

Inflectra was launched at risk at the end of last year. A patent trial expected to start by February 12 and run until February 24 will determine whether Celltrion, Inflectra’s manufacturer and Pfizer’s partner, will pay a heavy penalty for Pfizer’s eagerness (Pfizer takes risk for biosimilar followers, October 18, 2016).

According to Wells Fargo analysts, court filings made at the end of January note that Celltrion has started purchasing the cell media used in the antibody’s production in Singapore rather than from its previous US supplier. This activity is, according to the analysts, outside US legal control and therefore might not infringe the patent, leaving J&J without a case.

If this is confirmed by the court, the flip side is that Celltrion might have to get separate FDA approval for the new cell media.

There are two sources of hope for J&J, however. The court could decide that, even though Celltrion is no longer infringing J&J’s patent, its past infringement – when it was buying its raw materials from the US supplier – gave it an unlawful “head start” for which it should pay.

Alternatively the appellate courts might reinstate the other patent that J&J previously asserted unsuccessfully in this litigation. Sadly for the New Jersey group, Wells Fargo’s legal eagles suggest that both of these possibilities are “low-likelihood paths”.

On J&J’s fourth-quarter call it was made clear that Remicade was showing signs of early pressure from biosimilars, with global fourth-quarter sales down 3.3%; US sales fell 1.7%.

Sellside consensus from EvaluatePharmacalculates that Remicade’s US sales will begin to fall next year and will almost halve by 2022, to $2.6bn. Inflectra’s US sales are forecast to reach $277m by 2022.

Side-effect worry

Meanwhile, Ardelyx’s phase III study is the first of two pivotal trials for tenapanor, which is intended to treat hyperphosphataemia in end-stage renal disease patients on dialysis. The protocol calls for eight weeks' treatment, followed by a four-week randomized withdrawal. During this time patients either stay on their current dose or are switched to placebo.

The project is administered at 3mg or 10mg twice a day, or at a varied dose that starts at 30mg twice a day and titrates down. The primary endpoint is placebo-adjusted change in serum phosphate during the withdrawal period.

In a phase II trial, run by Ardelyx's then-collaborator AstraZeneca (NYSE:AZN), the 10mg and 30mg doses showed a statistically significant decrease in serum phosphate levels versus placebo. The treatment period in the trial was four weeks. However, the primary concern was the rate of diarrhoea, which was much higher than expected and caused Ardelyx’s shares to tank 48% over two days.

Three months later, a phase II trial failed in chronic kidney disease patients with type 2 diabetes and albuminuria. Shares fell 24%. Consensus forecasts from EvaluatePharma peg 2022 sales at $952m, with a hefty $613m allocated to partnering the asset outside the US.

Two phase III trials in tenapanor's bigger indication, constipation-predominant irritable bowel syndrome, are also due to read out this year. Again diarrhea rates were higher in prior trials, although not to the level seen in hyperphosphataemia. No doubt this side-effect will be carefully monitored in upcoming studies.

Study

Trial ID

Phase II in ESRD patients

NCT01764854

Phase III in ESRD patients

NCT02675998

IBS-C trials

NCT02621892 (T3MPO-1)

NCT02686138 (T3MPO-2)