Walgreens Boots Alliance Inc. WBA, 2.54% has expanded its contactless curbside delivery service to all of its 8,600 stores nationwide, the pharmacy retailer announced Tuesday. Purchases are available within an hour and the service is available between 9 a.m. and 9 p.m. local time. On Monday, Walgreens announced that its chief executive had resigned. Walgreens stock has fallen 31.5% for the year to date while the S&P 500 index SPX, -0.01% has edged up 0.2% for the period.
Tuesday, July 28, 2020
Gilead’s Kite gains some height after second CAR-T approval in US
Gilead’s $11.9 billion purchase of Kite Pharma in 2017 didn’t follow the script, with two big write-downs in the value of the asset since then, but a fresh approval for a CAR-T therapy could claw back some value.
Late last week, the FDA approved Kite’s Tecartus (brexucabtagene autoleucel; formerly KTE-X19) as a treatment for mantle cell lymphoma (MCL) patients who have failed earlier lines of therapy, giving the company a second approved cell therapy – and the first without direct competition in the market.
Tecartus will launch with a $373,000 list price, around the same as Gilead/Kite’s first CAR-T – non-Hodgkin’s lymphoma therapy Yescarta (axicabtagene ciloleucel) – which was approved back in 2017.
Yescarta launched with blockbuster sales predictions but has failed to make much headway in the market, bringing in just over $450 million last year with flat quarter-on-quarter growth.
It competes in some indications with Novartis’ rival Kymriah (tisagenlecleucel) product, which has also underwhelmed since launch with sales of less than $300 million in 2019.
Both drugs have been held back by small target populations and a lengthy treatment process that carries no small amount of toxicity risk.
Yescarta’s lacklustre performance caused Gilead to take an $800 million charge in the fourth quarter, which came after an $820 million write-down a year earlier as the company downgraded the value of Yescarta and Kite’s CAR-T pipeline.
Gilead chief executive Daniel O’Day has talked about a looser relationship with Kite – perhaps with its own CEO – suggesting Gilead is looking elsewhere for growth potential.
Tecartus is the first CAR-T to be approved for MCL, a rare and aggressive form of NHL, and had been awarded breakthrough status by the FDA based on results of ZUMA-2, an open-label study that found an 87% response rate with the CAR-T including 62% complete responses. That’s considered an impressive level of efficacy considering the hard-to-treat patient population.
In autologous CAR-T therapy, the patient’s T cells are harvested and genetically modified to include a new gene that helps then target and kill lymphoma cells, and the modified T cells are then infused back into the patient.
It’s a process that can take at least a couple of weeks, and carries a risk of side effects including cytokine release syndrome (CRS), which can cause fever and flu-like symptoms and can be life-threatening.
Tecartus has a boxed warning on the label for CRS, as 18% of patients treated with the therapy in the ZUMA-2 trial developed the side effect at a level of grade 3 or higher. The warning also covers neurological toxicities, which were seen in 37% of patients.
The CAR-T is currently under review in the EU and has been granted priority medicines (PRIME) designation by the EMA for relapsed or refractory MCL, so could get approval there before year-end.
Meghan Gutierrez, chief executive of the Lymphoma Research Foundation, said that the approval builds on progress in the treatment of MCL with an increase in clinical trials for the blood cancer that “we hope will continue to improve treatment strategies” for patients.
Recent approvals for MCL include AstraZeneca’s Calquence (acalabrutinib) and BeiGene’s Brukinsa (zanubrutinib), two BTK inhibitors used as second-line therapies after initial therapy chemotherapy or proteasome inhibitors such as Takeda’s Velcade (bortezomib).
Meanwhile, Gilead/Kite is also looking ahead to the readout later this year of ZUMA-7 – a trial that could advance Yescarta up the treatment pathway for diffuse large B cell lymphoma (DLBCL) and – they hope – restore some sales growth.
A turn-up for Spectrum’s book
Poziotinib unexpectedly succeeds in a lung cancer niche, but competition from Takeda must be tracked closely.
After the failure of Spectrum’s poziotinib in a potentially pivotal study cohort in December hopes for the trial’s remaining arms were low. But analysis of the second cohort yesterday yielded a positive outcome, sending the company’s stock up 30% this morning.
Spectrum looks set to file on the latest data, pending agreement with the US FDA, though the niche in which poziotinib has succeeded, a subset of a subset of non-small cell lung cancer, is more poorly diagnosed and even smaller than the one in which it failed. Investors also need to remember the threat of Takeda’s competing and potentially more efficacious project.
For now, however, Spectrum can bask in some glory. In its multi-cohort Zenith20 trial poziotinib has yielded an independently adjudicated overall remission rate of 28% among 90 second-line or later NSCLC subjects with a Her2 exon 20 insertion.
Zenith20 is designed so almost any one of its arms can be registrational, and Spectrum confirmed that it would request a meeting with the FDA to discuss filing. The benchmark Spectrum had set in cohort 2 of the uncontrolled trial was a lower bound of 17%, and as the 95% confidence interval for the ORR was 18.9-38.2% it deemed this part of the trial a success.
| Cohort | Setting | Subjects | Data |
| 1 | Relapsed, EGFR exon 20 insertions | 115 | Fail: confirmed ORR 14.8%, mDOR 7.4mth |
| 2 | Relapsed, Her2 exon 20 insertions | 90 | Success: confirmed ORR 27.8%, mDOR 5.1mth |
| 3 | 1st-line EGFR exon 20 insertions | 70 | Due late 2020 |
| 4 | 1st-line Her2 exon 20 insertions | 70 | – |
| 6 | EGFR Tagrisso failures | 30 | – |
| 7 | Atypical EGFR or Her mutations | 30 | – |
| Source: Spectrum. ORR=overall remission rate; mDOR=median duration of response. | |||
Zenith20’s first cohort, relapsed NSCLC driven by EGFR exon 20 insertions, had failed, yielding an ORR of just 15%. On a call today Spectrum confirmed that both analyses had been verified by the same central review committee, but it could offer no explanation for the disparate result, beyond citing “different receptor targets”.
This raises fresh questions about why poziotinib, a Her2 inhibitor, was taken forward in this NSCLC niche; Spectrum had initially been looking at breast cancer, but was persuaded otherwise by MD Anderson’s Cancer Moon Shots programme, which had preclinically identified poziotinib as a potent agent against exon 20 mutations (The first test of Spectrum’s shift, November 28, 2019).
Spectrum investors will be aware of a key competitor in the exon 20 insertion niche: Takeda’s mobocertinib (TAK-788), which at Asco 2019 yielded a 43% ORR, with 7.3-month median duration of response in EGFR exon 20 insertion-mutant NSCLC.
On a cross-trial basis these data clearly beat Zenith20’s cohort 1. Unfortunately Takeda has not yet generated any results in Her2 exon 20 mutants, so a comparison against Spectrum’s latest dataset is not possible.
Niche
If Spectrum’s poziotinib strategy simply needs refining, then investors should be aware of how small the niche is. Takeda reckons 6% of EGFR-mutated NSCLC tumours have exon 20 insertions; Spectrum says this equates to 2.1% of NSCLC, versus just 1.5% for exon 20 insertions in Her2.
Thus the space Spectrum’s latest dataset could open up amounts to 6,500 US and EU patients a year, across all therapy lines. And a separate problem is that Her2 exon 20 mutations are generally not screened for at present, whereas thanks to drugs like Iressa and Tagrisso diagnosis of specific types of driver EGFR mutations is pretty standard.
Spectrum hopes that clinicians will start testing based on the data it has generated, but without a big partner to drive such an effort this is wishful thinking. Spectrum also surely needs some of Zenith20’s other cohorts to succeed to show that yesterday’s readout was not a fluke.
Inhibrx steps back into the box for IPO
Inhibrx (INBX) has filed a new preliminary prospectus for an IPO.
It initially filed a preliminary prospectus in June 2019 but withdrew it five months later.
The La Jolla, CA-based biotech develops drugs directed to validated targets based on its single domain antibody platform, adding that it believes that its protein engineering technologies can overcome the limitations of other therapies. It currently has three oncology programs in Phase 1 development: INBRX-109, a tetravalent agonist of a receptor called DR5; INBRX-105, an anti-PD-L1 monoclonal antibody that is a conditional agonist of a receptor called 4-1BB and INBRX-103, an anti-CD47 monoclonal antibody.
Synairgen inhaled interferon beta shows significant benefit in COVID-19
UK-based nano cap Synairgen (LON: SNG) (OTCPK:SYGGF) has been a star in Europe driven by the potential of its inhaled therapy for COVID-19.
Last week, shares rocketed 450% after the company announced preliminary data from a 101-subject Phase 2 study that showed treatment with nebulized interferon beta, licensed for use in multiple sclerosis, cut the risk of severe disease symptoms by 79% and reduced the average discharge time by 33%.
Despite the rally, the company still sports a very modest market cap of ~$69M.
FDA OKs Lilly coronavirus lab test
The FDA has signed off on emergency use of Eli Lilly’s (LLY +2.6%) qualitative (yes/no answer) molecular test for SARS-CoV-2. The use of laboratory developed test (LDT) is restricted to the company’s diagnostics lab at its corporate campus in Indianapolis.
AstraZeneca diabetes drug shows promise in severe kidney condition
AstraZeneca’s diabetes treatment has shown promise in a late-stage trial to help to slow chronic kidney disease, putting it on track for possible expanded approvals ahead of rival drugs.
The British drugmaker said on Tuesday that the treatment – Farxiga – which is used for the most common form of diabetes, helped to improve renal function or reduced the risk of death compared with a placebo in diabetic and non-diabetic patients in a study.
Diabetes is known to have knock-on effects for the heart and kidneys, prompting many drugmakers to test their diabetes treatments on conditions affecting these organs.
Farxiga is part of the SGLT2-inhibitor class of antidiabetics which also includes Eli Lilly and Boehringer Ingelheim’s Jardiance and Johnson & Johnson’s Invokana.
Earlier this year, the U.S. Food and Drug Administration put Jardiance up for a speedy review for a similar setting, but the drug has yet to receive approval. Farxiga was granted this status by the FDA last year.
Chronic kidney disease (CKD) is a serious, progressive condition which affects nearly 700 million people worldwide, and has limited treatment options.
The positive data from AstraZeneca’s late-stage DAPA-CKD trial also comes nearly three months after U.S. regulators approved Farxiga as a medicine for heart failure in certain patients, regardless of their diabetes status.
Farxiga had sales of $1.54 billion (1.2 billion pounds) in 2019, making it among AstaZeneca’s top five treatments in terms of revenue.
The AstraZeneca trial also met all of its secondary goals, the company said.
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