Upcoming Events – Kymriah’s label extension and Mallinckrodt’s FDA panel


Welcome to your weekly digest of approaching regulatory and clinical readouts. Having secured the first approval for a CAR-T product Novartis is going for a second indication for Kymriah – the immunotherapy is due an FDA decision in May in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The Swiss firm will be hoping to get a first-time greenlight from the regulatory agency in what is a much bigger indication.

While Novartis is aiming for a second approval with Kymriah, Mallinckrodt has its eyes set on a first. The company’s lead pipeline product, Stanate, is going up before an advisory panel on May 3. A positive recommendation will pave the way for the product to become the first pharmacological therapy approved to treat severe jaundice in babies, one of the biggest cause of readmission to hospital among newborns.

Kymriah’s next indication

Senior executives from Novartis have already noted that Kymriah needs to work in other blood cancers to be a “really big product”, so any approval in DLBCL will help. The product is already approved in B-cell precursor ALL and consensus forecasts from EvaluatePharma are predicting $949m of sales in 2022, all assigned to the ALL indication. Presumably, numbers could rise following an approval in DLBCL.

Given the outcome of the phase II Juliet study, which was used for registration purposes, many are expecting approval. The trial showed an overall response rate (ORR) of 37% at six months. Gilead’s Yescarta, which was approved in DLBCL last October, had an ORR of 41% at six months (Ash 2017 – Transcend fails to prevent Juno’s second collapse, December 12, 2017).

Comparing pivotal CAR-T studies in lymphoma
Company Gilead Novartis
Product Yescarta Kymriah
Study Zuma-1 Juliet
Best ORR 82% (101) 53% (81)
Best CR 54% (101) 40% (81)
3mth ORR 44% (62) 38% (81)
3mth CR 39% (62) 32% (81)
6mth ORR 41% (101) 37% (46)
6mth CR 36% (101) 30% (46)
Note: numbers in brackets refer to total subjects in each given cohort. Source: Ash 2017 presentations. 

So, with broadly similar efficacy between the two products the battle between Kymriah and Yescarta could come down to pricing. Yescarta currently has a list price of $373,000 vs $475,000 for Kymriah. Novartis has already proposed outcomes based pricing for Kymriah in ALL – pledging not to charge for the treatment if a patient does not respond after one month. If it does the same in DLBCL then it could take market share from Yescarta, as Gilead has not proposed this option.

Saving babies

With mounting payer pushback causing sales to fall for its main product, Acthar Gel, Mallinckrodt needs to broaden its marketed drug portfolio (Spotlight – Slowing Acthar sales are a warning about rising patient costs, November 9, 2017).

Its lead pipeline hope, Stanate, will go before an FDA panel on May 3. The injection is used to treat newborns at risk of developing severe jaundice.

Jaundice is common among newborns – 50% of full-term and 80% of pre-term infants develop the disorder in the first week of life, with most symptoms disappearing within two weeks without treatment. But the severe form of the disorder, known as hyperbilirubinemia, can lead to neurological complications, including encephalopathy or irreversible brain damage. It is this small patient population that Mallinckrodt is targeting.

If approved, Stanate would be the first pharmacological option for severe jaundice in the US. Phototherapy is the current standard of care to reduce bilirubin levels, but is often not effective in severe cases. More invasive options include exchange blood transfusion or intravenous immunoglobulin.

Stanate works by inhibiting haem oxygenase, an enzyme involved in the production of bilirubin. It is administered by a single intramuscular injection with the effects lasting for between seven and eight days after treatment.

The product was developed by Infacare Pharmaceutical, which Mallinckrodt bought last September for $80m upfront. EvaluatePharma’s consensus sales forecasts for Stanate currently sit at $73m for 2022.

With fast track designation, a clear unmet need and two positive phase II trials it might be tempting to see Stanate as a shoo-in. But given the heightened vulnerability of the patient population the FDA panel will place significant emphasis on safety, and any slips here will be costly.

That said, so far there have been no reported serious adverse events associated with Stanate, meaning Mallinckrodt might have a new marketed product on its hands by the August 22 PDUFA date.

To contact the writers of this story email Joanne Fagg and Lisa Urquhart in London at joannef@epvantage.com or lisau@epvantage.com or follow @ByJoFagg or @ByLisaU on Twitter 

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