Friday Five – the pharma week in review

Important late- and mid-stage data which could have a significant impact on the rheumatoid arthritis and psoriasis markets, respectively, was unveiled this week, as were late stage results for the combination of Bavencio and Inlyta which are poised to intensify competition in the renal cell carcinoma market. European roll-out of CAR-T continues but Amgen highlighted new data showing the potential benefits of bispecific antibodies as an alternative form of therapy and what next at Gilead?

 

When AbbVie walked away from Galapagos' filgotinib three years ago, Gilead Sciences smelt an opportunity; enough of one to part with $300 million upfront to in-license the JAK inhibitor, which is being studied across a catalogue of immunological indications.

This week, initial Phase III data in the largest of these - rheumatoid arthritis (RA) - were announced, confirming filgotinib to be at least as effective as other JAK inhibitors including AbbVie's own upadacitinib, the molecule it chose to prioritise development of back in 2015.

Side-effect data for filgotinib, at least in this first pivotal-stage trial, also appear to be cleaner than other JAK inhibitors, provisionally supporting a view that greater target specificity (30 fold more against JAK1 versus JAK2) may confer a superior safety profile.

With safety set to be a key battleground, this could prove advantageous if filgotinib is to overcome the significant sales and marketing presence AbbVie enjoys through the Humira franchise.

See - ViewPoints: Gilead and Galapagos stay the course with latest filgotinib update

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The sizeable revenue forecasts attached to JAK inhibitors in RA reflect in part the oral dosing of these agents, which have emerged on a treatment landscape now dominated by injectable biologic therapies.

A similar dynamic is yet to fully occur in the psoriasis market, but that might be about to change. Bristol-Myers Squibb has already pushed its oral agent BMS-986165 into pivotal-stage testing and this week presented the Phase II data that convinced it to do so. Notably, BMS-986165 inhibits TYK-2, a sub-class within the JAK family.

The one oral psoriasis agent that has made a commercial splash in recent years is Celgene's Otezla, with much of its success owed to oral dosing and a safe toxicity profile, which offset lower efficacy. 

One of the currently enrolling Phase III trials will pitch BMS-986165 against Otezla; new data for Bristol-Myers Squibb's agent shows why it is confident enough to take on the one oral incumbent with efficacy appearing to be superior and no obvious safety concerns. The company also confirmed this week that it plans to initiate Phase II studies in ulcerative colitis and psoriatic arthritis.

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Pfizer and Merck KGaA announced this week that the combination of Bavencio (their co-marketed PD-L1 inhibitor) and Pfizer's targeted cancer therapy Inlyta significantly improved progression-free survival (PFS) versus Pfizer's older drug Sutent in first-line renal cell carcinoma patients. They plan a US regulatory filing based on these data.

See - Merck KGaA, Pfizer say combination of Bavencio, Inlyta improves PFS versus Sutent in kidney cancer study

Full results have yet to be disclosed, but approval of a second combination could further limit use of Exelixis' Cabometyx in first-line patients; Bristol-Myers Squibb's pairing of the immunotherapies Opdivo and Yervoy has reportedly enjoyed strong adoption since gaining approval in the US, though European approval remains on hold.

Broad key opinion leader backing and US adoption of the Opdivo/Yervoy combination has occurred despite the fact that detailed pivotal-stage trial results show its clinical benefit was driven by PD-L1 positive, low- and poor-risk patients.

The combination of Bavencio and Inlyta has also reportedly hit its PFS endpoint regardless of PD-L1 expression, which must have come as something of a surprise. After starting its Phase III trial, Pfizer significantly expanded the cohort of patients being tested to allow for prospective PD-L1 analysis.

Further analysis coming next week - KOL Views: Sizing up the opportunity for Bavencio/Inlyta in front-line RCC

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Commercialisation of CAR-T products may now be a pan-regional affair but some companies believe that bi-specifics may prove more compelling when efficacy and convenience is taken into account.

On an investor call Thursday to discuss its R&D pipeline, Roche was keen to talk up early stage data for its CD20/CD3 bispecific antibody mosunetuzumab in heavily pre-treated diffuse large B-cell lymphoma (DLBCL) patients, including one prior CAR-T patient who achieved a complete response to Roche's therapy. This was sufficiently durable to subsequently allow allogeneic transplant, the company added.

And earlier in the week Amgen showed off new data from five multiple myeloma patients treated with its BCMA/CD3 targeted antibody AMG-420. While the data are early and need to be replicated in a larger study cohort, they suggest a potential competitive threat has emerged for other companies targeting BCMA to treat myeloma, whether this is with a CAR-T (such as bluebird bio) or antibody drug conjugate (GlaxoSmithKline).

See ViewPoints: Amgen takes a BiTE out of BCMA competition

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The pending departure of Gilead Sciences' CEO and chairman may have already pushed the company into a semi state of transition, but that did not stop it from inking a deal with Precision BioSciences this week focused on the development of hepatitis B therapies using gene editing.

Gilead has been transformed of course by its success in the field of hepatitis C, whereby its efforts to largely cure this disease with the launches of Sovaldi and Harvoni saw company revenues grow sharply over a three-year period.

See ViewPoints: Gilead positioning for a second shot at hepatitis

Its hepatitis C sales are now declining, but expectations remain high for a hard reset by new management that will set Gilead on course for its next growth phase. The company has invested heavily to find treatments for non-alcoholic steatohepatitis (NASH), looked to build credibility in the oncology market through the acquisition of CAR-T specialist Kite Pharma and is now eyeing up hepatitis B.

All interesting areas of drug development; when the CEO comes in will they stick or twist?       

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