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Pfizer’s breast cancer drug Ibrance fails late-stage study

(Reuters) – Pfizer Inc said on Friday its cancer drug Ibrance did not meet the main goal in a late-stage trial in patients with a type of breast cancer, the latest setback in the company’s attempt to expand the use of the drug to treat early stages of the disease.

The latest development comes after an independent data monitoring committee said in May a similar trial comparing Ibrance plus an endocrine therapy to a standalone endocrine therapy to treat early-stage breast cancer was unlikely to meet the main goal.

Ibrance is already approved in the United States to treat certain adult patients with advanced breast cancer which has spread to other parts of the body. The drug has not yet been approved for treating early stages of the disease.

This puts the drug at a relative disadvantage to rival Eli Lilly and Co, which in June posted data showing that its drug Verzenio, met the trial goal of reducing the risk of early-stage breast cancer from recurring.

“Today’s data leaves Lilly’s Verzenio as the clear winner in the adjuvant space for now, giving Verzenio a blockbuster opportunity in a potential early breast cancer indication,” Cantor Fitzgerald analyst Louise Chen said.

In the late-stage trial, Ibrance failed to meet the main goal of increasing the amount of time patients survived without their cancer returning.

Lilly’s shares were up 1% at $155.10 in pre-market trading, while Pfizer’s stock was flat at $36.90.

(Reporting by Manojna Maddipatla in Bengaluru; Editing by Shailesh Kuber and Shounak Dasgupta)

Source Article

Kaletra Again Fails for Moderate-to-Severe COVID-19

Lopinavir-ritonavir (Kaletra), a protease inhibitor mainly used for HIV, did not reduce mortality or speed recovery from COVID-19, Britain’s large RECOVERY trial affirmed.

Mortality at 28 days was 23% among the hospitalized COVID-19 patients randomized to lopinavir-ritonavir (400 and 100 mg, respectively, for 10 days or until discharge) compared with 22% in the usual care group (rate ratio [RR] 1.03, 95% CI 0.91–1.17).

The same was true for all prespecified subgroups, including sex, age, duration of illness, degree of respiratory support at baseline, and predicted mortality risk, Peter Horby, MD, PhD, of the University of Oxford, England, and colleagues reported in The Lancet.

Secondary endpoints likewise were similar with lopinavir-ritonavir and usual care:

  • Time to hospital discharge among survivors (median 11 days in both groups)
  • Proportion discharged alive within 28 days (RR 0.98, 95% CI 0.91-1.05)
  • Invasive mechanical ventilation or death for those not intubated at baseline (RR 1.09, 95% CI 0.99-1.20)

RECOVERY, a U.K.-based pragmatic trial in which hospitalized patients are randomized to various open-label treatments, previously turned up the first mortality benefit in COVID-19 with dexamethasone. Other arms include tocilizumab (Actemra), convalescent plasma, REGN-CoV2 combination monoclonal antibodies, and azithromycin, while a hydroxychloroquine arm was terminated.

The 5,040-patient trial “provides a more solid evidence base regarding possible lopinavir–ritonavir treatment effects” than the prior 199-patient trial from China with similar findings and interim results from the WHO Solidarity trial, noted an accompanying editorial.

Those earlier results along with the drug’s well-documented adverse effects and drug interactions led to a National Institute of Health recommendation against lopinavir-ritonavir use for hospitalized COVID-19 patients outside of clinical trials.

The many other clinical care guidelines that have recommended lopinavir-ritonavir should now be updated, Horby’s group urged.

Still, early antiviral treatment could be worth testing for mild cases of COVID-19 or post-exposure prophylaxis in high-risk populations, noted editorialists Bin Cao, MD, of the National Clinical Research Center for Respiratory Diseases in Beijing, and Frederick Hayden, MD, of the University of Virginia School of Medicine in Charlottesville.

“Given the efficient replication of SARS-CoV-2 shortly after infection and the association between mortality and viral RNA loads at diagnosis, it is possible that early use of sufficiently potent antiviral drugs would be an important determining factor in clinical outcomes, although few early intervention trials have been completed,” Cao and Hayden wrote.

Also, they argued, antiviral and immunomodulator combinations should be studied, since monotherapy might not be enough for moderately to severely ill patients admitted to hospital with COVID-19.

Limitations of the RECOVERY trial data, Horby and co-authors said, included enrollment of few intubated patients, “as there were difficulties in administering treatment to patients who could not swallow,” such as potential to block feeding tubes with crushed tablets and unreliable bioavailability.

Disclosures

The study was funded by the Medical Research Council and National Institute for Health Research.

The researchers disclosed no conflicts of interest.

Cao disclosed having worked closely with an article author on influenza and COVID-19 therapeutic studies. Hayden reported personal fees from University of Alabama Antiviral

HCQ Fails as COVID-19 Pre-Exposure Prophylaxis for HCPs

There was no clinical benefit to hydroxychloroquine (HCQ) as COVID-19 pre-exposure prophylaxis among a small sample of hospital-based healthcare professionals, a randomized trial stopped early for futility found.

Participants randomized to receive HCQ daily for 8 weeks had no significant difference in infection rates versus those randomized to receive placebo (6.3% vs 6.6%, respectively, P >0.99), reported Ravi Amaravadi, MD, of the University of Pennsylvania in Philadelphia, and colleagues.

While median change in QTc baseline did not differ, overall adverse events were significantly more common in the HCQ arm than the placebo group, the authors wrote in the study online in JAMA Internal Medicine.

They noted that the trial enrolled 123 participants of a planned 200, but was terminated early for futility. After the second interim analysis, when 100 participants completed the study, four HCQ participants and three placebo participants converted to positive SARS-CoV-2 status, so the data safety monitoring board recommended early termination of the study.

HCQ has been out of the news recently, but researchers pointed to a study examining the drug as post-exposure prophylaxis with a 5-day course. While it did not demonstrate clinical benefit, the authors noted key limitations to this trial — namely that the primary outcome was “symptoms consistent with infection” and that most patients did not have infection assessed via reverse-transcriptase polymerase chain reaction (RT-PCR) testing. This raised concerns about type II error from asymptomatic participants, the researchers said.

They sought to examine daily HCQ as pre-exposure prophylaxis in hospital-based healthcare workers via RT-PCR testing of nasopharyngeal swabs, as well as serologic antibody testing from participants at baseline and at 4 and 8 weeks of treatment.

The Prevention and Treatment of COVID-19 With Hydroxychloroquine (PATCH) trial took place at two teaching hospitals in Philadelphia from April 9 to July 14. Hospitals had uniform policies regarding healthcare worker use of personal protective equipment, including masks, eyewear, and gowns and screening patients for COVID-19 symptoms.

Eligible participants included physicians, nurses, certified nursing assistants, emergency technicians, and respiratory therapists who worked 20 hours or more per week in hospital-based units, had no history of SARS-CoV-2 infection nor COVID-19 symptoms in the 2 weeks prior to enrollment.

The primary outcome was the rate of conversion to SARS-CoV-2-positive status via nasopharyngeal swab during 8 weeks of study participation.

The 132 initial participants who were randomized were a median age of 33, almost 70% were women, and 83% were white. More than half worked in the emergency department, while 37% worked in the internal medicine ward. About two-thirds of participants were nurses, while 21% were physicians.

Overall, 64 participants in the HCQ arm and 61 in the placebo arm were evaluable for the primary outcome, the authors noted, though 12 HCQ participants and 10 placebo participants discontinued study treatment early.

There were eight infections throughout the study period, none requiring hospitalization. All were either asymptomatic or had “mild disease and fully recovered.”

At the end of the study period, the authors noted, four SARS-CoV-2-positive participants treated with HCQ