Upcoming events – FDA approvals due for Maviret and Besponsa

Welcome to your weekly digest of approaching regulatory and clinical readouts. Abbvie’s hepatitis C project Maviret is considered odds-on to receive FDA approval by its August PDUFA date, but this pan-genotypic therapy must achieve a label permitting a short treatment duration if it is to compete in a busy market (see table below).

Pfizer’s acute lymphoblastic leukaemia treatment Besponsa is also due to come up before the US regulators next month. The antibody-drug conjugate targets CD22, an antigen of particular interest for followers of CAR-T.

12 week vs eight

Maviret is a fixed-dose combination of glecaprevir and pibrentasvir for which a US approval decision is due next month. It is a once-daily treatment consisting of three tablets. Abbvie is seeking approval for an eight-week treatment schedule in patients with genotypes 1-6 without cirrhosis and those who are new to treatment across all genotypes.

It is also intended as an option for patients with compensated cirrhosis, those with chronic kidney disease (including those on dialysis) and patients with genotype 3. In some of these subpopulations it could be approved as a 12-week treatment.

It received a positive CHMP recommendation in June, with a European Commission decision due in the third quarter. The recommendation was swayed by data showing 97.5% cure rates with eight weeks of Maviret treatment.

With a hepatitis C market near saturation competition is intense, but combination therapies are gaining ground as they cover a greater number of genotypes.

Maviret is forecast to become the top pan-genotypic product by 2022, but to achieve this Abbvie will need to get the eight-week duration on its label. Sales are expected to reach $1.2bn, according to consensus from EvaluatePharma, with an NPV of $4bn, equal to 4% of Abbvie’s market cap.

Other combination products fighting for a share include Gilead’s 12-week regimen Epclusa. Gilead also gained US approval earlier this month for its triple combination Vosevi as salvage therapy. Vosevi is the first pill approved for patients who have not been cured after treatment with an NS5A inhibitor.

It was approved as a 12-week treatment in the US, but the label does not include the eight-week treatment duration that was previously recommended in Europe. Abbvie will hope to avoid succumbing to the same fate.

CD22 target

Last month Pfizer’s inotuzumab ozogamicin, trademarked Besponsa, gained European approval as a monotherapy for adults with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukaemia (ALL). This came on the back of the phase III Ino-Vate trial in which Besponsa achieved a higher remission rate than chemotherapy.

In the US it has breakthrough therapy designation, with a PDUFA date in August. Besponsa’s approval should be of interest to followers of CAR-T therapies, some of which target the same CD22 antigen. Although an antibody-drug conjugate is unlikely to elicit the same efficacy as CAR-T, Besponsa could reduce the market size if it is given as an earlier line of therapy, since patients relapsing on it by antigen escape would no longer be candidates for an anti-CD22 CAR-T.

Sales forecasts are modest, currently sitting at $347m by 2022, according to consensus from EvaluatePharma. UCB has worldwide royalties.

Notably, Besponsa’s cytotoxic payload ozogamicin is the same as that used in the company’s Mylotarg. This was pulled in 2010 after 10 years on the market owing to concerns about toxicity and lack of benefit in acute myeloid leukaemia, but recently earned a positive adcom vote that could see its US re-approval by September.

To contact the writer of this story email Joanne Fagg in London at [email protected] or follow @ByJoFagg on Twitter