The first and only FDA-approved intravenous immunoglobulin with two maintenance dosing options for CIDP
Pfizer Inc. (NYSE: PFE) today announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental Biologics License Application (sBLA) for PANZYGA® (Immune Globulin Intravenous [Human] – ifas 10% Liquid Preparation) to treat adult patients with a rare neurological disease of the peripheral nerves called chronic inflammatory demyelinating polyneuropathy (CIDP). PANZYGA is the only intravenous immunoglobulin (IVIg) with two FDA-approved maintenance dosing options for CIDP, helping to meet the clinical needs of patients. PANZYGA can also be administered at infusion rates up to 12 mg/kg/min.
“Each patient with CIDP has different treatment needs, and we have found that having one approved dosing option is not always optimal,” said Angela Lukin, Global President, Hospital Business Unit, Pfizer Inc. “The approval of this new indication with additional dosing options helps address an unmet patient need by providing healthcare providers with the ability to choose an approved dose that's right for patients.”
CIDP is a rare disorder of the peripheral nerves characterized by gradually increasing symmetrical motor and sensory loss and weakness associated with loss of deep tendon reflexes. It is caused by damage to the covering of the nerves, called myelin. The gradual onset of CIDP can delay diagnosis by several months or even years, resulting in significant nerve damage that may limit and delay the response to therapy. Most individuals will require long term treatment; nearly a third of CIDP patients will progress to wheelchair dependence if left untreated. Early recognition and proper treatment are critical in helping patients avoid a significant amount of disability.
The U.S.Food and Drug Administration (FDA)approved Cosela (trilaciclib) as the first therapy in its class to reduce the frequency of chemotherapy-induced bone marrow suppression in adults receiving certain types of chemotherapy for extensive-stage (when the cancer has spread beyond the lungs) small cell lung cancer. Cosela may help protect bone marrow cells from damage caused by chemotherapy by inhibiting cyclin- dependent kinase 4/6, a type of enzyme.
"For patients with extensive-stage small cell lung cancer, protecting bone marrow function may help make their chemotherapy safer and allow them to complete their course of treatment on time and according to plan," said Albert Deisseroth, M.D., Ph.D., supervisory medical officer in the Division of Non-Malignant Hematology in the FDA's Center for Drug Evaluation and Research. "Today's approval of Cosela will give patients a treatment option that can reduce the occurrence of a common, harmful side effect of chemotherapy."
Study demonstrated objective response rates of 38% in all patients, 62.5% in patients with renal cell carcinoma and 42.4% in patients with urothelial carcinoma –
– Data to be presented during the 2021 American Society of Clinical Oncology’s Genitourinary Cancers Symposium –
Exelixis, Inc. (NASDAQ: EXEL) today announced positive final data for a phase 1 trial sponsored and conducted by the U.S. National Cancer Institute (NCI), including seven expansion cohorts, evaluating cabozantinib in combination with either nivolumab or nivolumab plus ipilimumab in patients with refractory metastatic genitourinary (GU) tumors. The data will be presented as part of the Rapid Abstract Session: Urothelial Carcinoma and Rare Tumors from 2:15 p.m. – 3:05 p.m. PT on Friday, February 12 at the 2021 American Society of Clinical Oncology’s Genitourinary Cancers Symposium (ASCO GU), which is being held virtually, February 11-13, 2021.
In the study, cabozantinib in combination with either nivolumab alone (n=64) or nivolumab plus ipilimumab (n=56) demonstrated an objective response rate (ORR) for all evaluable patients (n=108) of 38%, with an 11.1% complete response (CR) rate per the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
For the 33 patients with previously treated metastatic urothelial carcinoma (UC), the ORR was 42.4%, and the CR rate was 21%. The ORR for the 16 patients with previously treated metastatic renal cell carcinoma (RCC) was 62.5%. The ORR was 20% for patients with urachal adenocarcinoma (n=15), 85.7% for squamous cell carcinoma of the bladder (n=7) and 44.4% for penile carcinoma (n=9).
The median overall survival for the entire population was 15.9 months. Median progression-free survival was 5.5 months, and median duration of response was 22.8 months.
“We see a significant level of anti-tumor activity with an acceptable tolerability profile for the combination of cabozantinib with nivolumab or nivolumab and ipilimumab for this early phase trial across a broad range of GU malignancies,” said Andrea Apolo, M.D., Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health and the principal investigator of the trial. “This phase 1 study’s early results provided important information for the development of the phase 3 CheckMate -9ER study sponsored by Bristol Myers Squibb, of cabozantinib plus nivolumab versus sunitinib that recently reported improved progression-free survival, overall response, and overall response rate, leading to last month’s U.S. approval of the combination therapy of cabozantinib and nivolumab in first-line advanced renal cell carcinoma. The additional activity seen in other GU tumors support further research into the potential of cabozantinib combinations with immune checkpoint inhibitors in other advanced, intractable GU cancers.”
Early results from University of Oxford’s RECOVERY trial showed Roche’s immunosuppressant Actemra reduced deaths and the need for mechanical ventilation in severe COVID patients. Genentech’s Actemra is approved to treat rheumatoid arthritis and cytokine release syndrome resulting from chimeric antigen receptor-T cell therapy. Thedatawas posted online before peer-reviewed publication in the preprint archive medRxiv.
According to the findings, about half of the 4,116 adults in the trial added Actemra to the standard of care while the other half received the standard of care alone. Mortality improved from 33% in the 2,094 patients who did not receive Actemra to 39% in the 2,022 patients who did. Mortality dropped from 22% to 19% in patients that did not require a ventilator, and from 48% to 47% in patients who required mechanical ventilation.
The largest benefits were seen in patients receiving corticosteroids as part of the standard of care. Across both groups, 82% of enrolled patients received a corticosteroid, primarily dexamethasone. The mortality rate of patients who received a corticosteroid was 33%, which dropped to 27% for patients who added Actemra. In patients who did not receive a corticosteroid, Actemra increased mortality from 35% to 39%.
The study’s findings help detail a confusing picture based on earlier results. In January, results from a small study in Brazil suggested Actemra did not help patients with severe COVID-19. But larger, earlier trials suggested that Actemra decreased mortality and shortened recovery times in intensive care. In a Roche-sponsored study last September, Actemra decreased by 44% the likelihood patients would progress to mechanical ventilation or death compared to those receiving placebo plus standard of care.
Martin Landray, an author on the paper and a professor of medicine and epidemiology at University of Oxford, previously said he expected the results of this trial to help make “definitive decisions about exactly what the role of this drug is.” Earlier datafrom the RECOVERY trial last June showed dexamethasone alone decreased mortality among patients receiving either invasive mechanical ventilation or oxygen. That data contributed to the inclusion of dexamethasone in recommendationsfrom the National Institutes of Health as part of the standard of care treatment for COVID-19 patients requiring oxygen.
In the new preprint, the authors recommended updating clinical guidelines for COVID-19 patients with hypoxia and evidence of systematic inflammation. The data suggests treatment with a combination of a systemic corticosteroid and Actemra could reduce mortality by a third for patients on oxygen, and nearly a half for patients on more invasive mechanical ventilation, and the effects are additive, they said.
The authors also combined data from this trial with seven smaller, earlier ones that tested Actemra. Those trials did not show significant mortality benefit on their own, but “when all 8 trials are considered together, allocation to [Actemra] is associated with a 13% proportional reduction in 28-day mortality.”
Chinese authorities refused to provide World Health Organization investigators with raw, personalized data on early COVID-19 cases that could help them determine how and when the coronavirus first began to spread in China, the Wall Street Journal reported on Friday, citing WHO investigators.
The White House said on Friday it was not planning to require people to take COVID-19 tests before domestic airline flights after the prospect of new rules raised serious concerns among U.S. airlines, unions and some lawmakers.
Slideshow ( 2 images )
White House spokeswoman Jen Psaki said at a briefing on Friday that “reports that there is an intention to put in place new requirements, such as testing, are not accurate.”
Late on Friday, a spokeswoman for the Centers for Disease Control and Prevention said, “at this time, CDC is not recommending required point of departure testing for domestic travel.” She added the CDC “will continue to review public health options for containing and mitigating spread of COVID-19 in the travel space.”
CDC said last month the agency was “actively looking” at expanding mandatory COVID-19 testing to U.S. domestic flights.
Psaki spoke after the chief executives of major U.S. airlines, including American Airlines, Southwest Airlines and United Airlines, met virtually with White House COVID-19 response coordinator Jeff Zients.
The CDC on Jan. 26 began requiring negative COVID-19 tests or evidence of recovery from the disease from nearly all U.S.-bound international passengers aged 2 and older.
The White House and officials told Reuters this week that no formal order had been circulated and that officials were not expected to endorse requiring negative COVID-19 tests before domestic flights.
“We had a very positive, constructive conversation focused on our shared commitment to science-based policies as we work together to end the pandemic, restore air travel and lead our nation toward recovery,” Nick Calio, chief executive of the Airlines for America industry group, said in a statement after the meeting on Friday.
The White House held a separate interagency meeting on Friday to discuss other coronavirus issues and plans to hold further talks on other travel-related issues including potentially expanding international testing to land border crossings.
The meeting of airline CEOs, Zients and other administration officials involved in COVID-19 issues came after the industry strongly objected to the possibility of requiring COVID-19 testing before domestic flights.
Southwest Airlines warned such a requirement could put jobs at risk and a major aviation union said it could lead to airline bankruptcies.
One idea that has been under serious consideration is for the CDC to issue recommendations advising against travel to specific areas of the United States with high COVID-19 case loads, although those travel recommendations would not be binding, officials said.
The CDC currently has a broad recommendation discouraging all nonessential air travel.
Europe’s medicines regulator is planning to speed up assessments of any COVID-19 vaccines that are modified to protect against variants of the virus, the head of the agency’s COVID-19 task-force told Reuters on Friday.
FILE PHOTO: Doctor Bertram Wiedenmann (R), prepares the vaccination of a patient with AstraZeneca's COVID-19 vaccine at Berlin's former Tegel TXL airport, amid the spread of the coronavirus disease (COVID-19) in Berlin, Germany, February 10, 2021. Kay Nietfeld/Pool via REUTERS/File Photo
Marco Cavaleri, chair of the vaccine evaluation team at the European Medicines Agency (EMA), said there should be no need for lengthy large-scale trials like those needed to evaluate the first COVID-19 vaccines, since tweaks for new variants can be tested on smaller groups.
“We are working on updated guidelines, assuming that we cannot ask for large Phase III trials. This will allow us to go faster,” said Cavaleri.
“We will ask for much smaller trials, with a few hundred participants, rather than 30,000 to 40,000,” he told Reuters. He said the EMA would focus primarily on immune response data.
Drugmakers including Pfizer, Moderna and AstraZeneca have been testing their COVID-19 vaccines against several fast-spreading, more infectious variants of the novel coronavirus.
Variants which emerged in Brazil (known as P.1.), Britain (known as 20I/501Y.V1 or B.1.1.7) and South Africa (known as 20I/501Y.V2 or B.1.351) have already spread around the world, piling more pressure on governments struggling to tame the pandemic which has killed almost 2.5 million people.
These are the three major variants that are worrying scientists, with their spread raising the risk that newly-developed COVID-19 vaccines will need to be updated or tweaked to be effective against some variants, and that people may require one or more booster shots.
STREAMLINING
Last week, the U.S. Food and Drug Administration also said it is considering a rapid review process for the quick turnaround of new COVID-19 booster shots if variants emerge against which the vaccines do not provide protection.
Vaccine makers Pfizer and BioNTech, as well as AstraZeneca and Moderna, whose COVID shots have been authorised for emergency use in Europe, have said they are preparing for the possibility that variants will emerge that could require tweaks to their vaccines.
Normally, an EMA approval requires extensive studies with large numbers, starting with safety and ending with efficacy.
“We will also try to streamline regulatory procedures doing something similar to what happens with flu vaccines. In short, without the drugmakers having to submit all the preliminary data again”, Cavaleri said.
He added that the EMA is also aware that in the near future it may no longer be possible to do clinical trials with placebo for categories such as the elderly, due to rollout of current COVID-19 vaccines.
“In that case we could think about a head-to-head comparison with an already approved vaccine”, he said.
Cavaleri also told Reuters Johnson & Johnson will file its vaccine formal application in the next few days.
“Probably as early as next week”, he said, noting that the EMA has been conducting a rolling review of the vaccine for some time. “Mid-March is reasonable for the EMA decision,” he said.
The EMA, he added, has been in contact to date with about 50 pharmaceutical companies working on COVID vaccines.
Regarding the Russia’s Sputnik V vaccine, he said the agency is in constant contact with the company producing it.
“There is a constructive cooperation. If there are no problems with the answers we receive on the subject of the production phase, the rolling review could start within a matter of weeks,” he said
The EMA is also in contact with the Chinese companies developing vaccines, particularly Sinovac Biotech, but the process for the Chinese vaccine is a few steps behind the Russian one, he said.
