SHP465 back in front of the FDA and data for Venclexta

en years after the FDA first rejected SHP465 it is back in front of the regulators with a decision due by June 20. With new clinical data under its beltSHP465 will be needed to expand Shire’s ADHD franchise (see table below).

Also results are due mid-year for Abbvie’s Venclexta in chronic lymphocytic leukaemia. Already approved in a subset of patients the data could lead to an expanded label and offer a welcome revenue stream as the pressure from biosimilars approaches.

Decade later

SHP465 was originally before the regulators back in 2007 but additional trials were requested. Now the resubmission includes data from studies in paediatric patients (aged 6-17) and adult patients with ADHD.

After its setback SHP465 sat on the shelf until 2014 when Shire decided to start a new trial just five days before Abbvie’s takeout bid. The reasons for freezing and resuscitating the project aren’t clear but with forecast sales of $416m by 2022, according to consensus from EvaluatePharma, it is expected to be Shire’s sixth biggest growth driver.

The strength of SHP465 comes in its long duration; it is a once-daily treatment while otherADHD drugs are given more frequently. Shire hopes this will allow patients to stop using both an immediate and extended-release version of Adderall to achieve the same control. WhileSHP465 isn’t expected to reach the blockbuster numbers of Adderall or Vyvanse its last patent expires in 2029, six years after Vyvanse loses market exclusivity (More than ever Shire needs unusual focus on ADHD franchise, June 30, 2016).

Expansion

Venclexta gained a green light last year in the US in patients with relapsed/refractory CLL with the 17p deletion, a marker for highly aggressive disease. This chromosomal abnormality occurs in approximately 10% of patients with untreated CLL and 20% of patients with relapsed CLL.

Venclexta was approved under an accelerated pathway based on an overall response rate of 80%. It was the first FDA approved treatment to block B-cell lymphoma 2 (Bcl-2), a protein that allows cancer cells to evade cell death mechanisms and is overexpressed in many patients with CLL.

The phase III Murano trial, due to read out mid year, is not just restricted to patients with the 17p deletion. 389 patients with relapsed or refractory CLL previously treated with one to three lines of therapy were enrolled. Venclexta was given in combination with Rituxan compared withbendamustine and Rituxan. It has breakthrough therapy designation in this combination setting.

The primary measure is investigator-assessed progression-free survival up to disease progression or death, up to approximately 4.5 years.

Safety will be closely monitored as tumour lysis syndrome caused several deaths in early trials. Dosing adjustments were made and no more deaths have been reported since 2013. In trials, including Murano, increasing doses of Venclexta are given in a five week ramp-up period, starting at 20mg up to a maximum of 400mg.

Last year sales of Venclexta were $13m and according to consensus from EvaluatePharma. 2022 sales are forecast to reach $2.4bn. Venclexta was jointly developed by Roche andAbbvie in a deal that involves splitting US sales 50/50, and Abbvie paying undisclosed royalties to Roche on ex-US sales.

It is Abbvie’s fourth biggest growth driver, with its other CLL drug Imbruvica in first place.Imbruvica too started off in patients with the 17p deletion and is now also used in first-line CLL.

As the threat of Humira biosimilars continues to hang over Abbvie, expanding Venclexta’s use would provide some consolation. A number of other combination studies are ongoing including its use with Gazyva and Imbruvica, with trials in multiple myeloma, acute myeloid leukaemia and mantle cell lymphoma.