Christine Blank

Merck’s Keytruda/chemotherapy combo treatment demonstrates a statistically significant and clinically meaningful improvement in overall survival (OS) for patients with triple-negative breast cancer (mTNBC), according to recent data.

The phase 3 KEYNOTE-355 study of Keytruda (pembrolizumab) in combination with chemotherapy (paclitaxel, nab-paclitaxel or gemcitabine/carboplatin) reduced the risk of death by 27% in patients with mTNBC whose tumors expressed PD-L1 compared with chemotherapy alone, Merck said in a 

There was an increase of 6.9 months in median overall survival with Keytruda plus chemotherapy compared with chemotherapy alone (23 months versus 16 months). The increase in overall survival was observed across the three chemotherapy choices.

European Society for Medical Oncology (ESMO) Congress 2021

currently approved under accelerated approval

 in the United States in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1.

“Metastatic TNBC has the worst survival prognosis among breast cancer subtypes, and there is an urgent need for treatment options that improve survival,” Hope Rugo, M.D., director, Breast Oncology and Clinical Trials Education, University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, said in a statement. “I am very encouraged to see these new overall survival data for the Keytruda combination.”

“With these new data, KEYNOTE-355 has now met both primary endpoints, improving progression-free and overall survival for the approximately 40% of patients from this trial with metastatic TNBC whose tumors expressed PD-L1,” Vicki Goodman, M.D., vice president, clinical research, Merck Research Laboratories, said in a statement.

The incidence of treatment-related adverse events was similar among patients in the two treatment groups, with Grade 3 to 5 adverse events occurring in 68% of patients in the Keytruda plus chemotherapy arm and nearly 67% of patients in the chemotherapy arm. Treatment-related adverse events led to discontinuation in 18.3% of patients in the Keytruda plus chemotherapy arm and 11% of patients in the chemotherapy arm.

Triple-negative breast cancer is a type of breast cancer that tests negative for estrogen hormone receptors, progesterone hormone receptors, and overexpression of human epidermal growth factor receptor 2. It is an aggressive type of breast cancer that characteristically has a high recurrence rate within the first five years after diagnosis. About 10% to 15% of patients with breast cancer are diagnosed with TNBC, which tends to be more common in people who are younger than 40 years of age, who are African American, or who have a 

Articles

Keytruda plus chemotherapy reduces the risk of death by 27% in patients with triple-negative breast cancer.

Merck Shares Significant Keytruda Breast Cancer Results

The FDA has accepted Axsome Therapeutics’ new drug application (NDA) for meloxicam-rizatriptan (AXS-07) for the treatment of acute migraine, bringing the novel investigational medication one step closer to full FDA approval.

Meloxicam-rizatriptan is a novel, oral, rapidly absorbed therapy for migraine, Axsome said in a 

. It is designed to provide rapid, enhanced and consistent relief of migraine, with reduced symptom recurrence, according to the company.


The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of April 30, 2022, for the NDA. 

“The FDA’s acceptance of the NDA for AXS-07 is an important milestone for Axsome as it brings us closer to potentially making this multi-mechanistic treatment available to migraine patients in need,” Herriot Tabuteau, M.D., CEO of Axsome, said in a statement.

The NDA is supported by results from two phase 3 randomized, double-blind, controlled trials that demonstrated elimination of migraine pain compared with placebo and active controls, the pharma maker said.

Migraines are common condition, with 15.3% of Americans aged 18 years or older reporting a migraine or severe headache in the previous three months, 

Meloxicam is a new molecular entity enabled by Axsome’s MoSEIC (Molecular Solubility Enhanced Inclusion Complex) technology, which results in rapid absorption while maintaining a long half-life. Meloxicam is a COX-2 preferential non-steroidal anti-inflammatory drug and rizatriptan is a 5-HT1B/1D agonist.

Meanwhile, OptumRx listed another investigational migraine medication, AbbVie’s ategoepant, as one of 

 for the third quarter of 2021. Ategoepant, expected to garner FDA approval in the third quarter, offers an additional oral treatment option for preventing migraine attacks.

The FDA has set a Prescription Drug User Fee Act target action date of April 30, 2022.

Investigational Oral Migraine Treatment Closer to Full FDA Approval

Boehringer Ingelheim and Eli Lilly’s blockbuster diabetes drug Jardiance (empagliflozin) received Breakthrough Therapy designation from the FDA as an investigational treatment for adults with heart failure with preserved ejection fraction (HFpEF).

Last fall, the FDA also granted Fast Track designation to the two pharma makers 

to develop a new heart attack-related indication

Sales of the popular diabetes medication increased 36% to $356.5 million in the second quarter of 2021, per 

The Breakthrough Therapy decision is based on results from the landmark EMPEROR-Preserved phase 3 trial, in which Jardiance demonstrated a 21% relative risk reduction for the composite primary end point of cardiovascular death or hospitalization for heart failure in adults with HFpEF compared with placebo, Boehringer Ingelheim and Lilly said in a 

HFpEF accounts for about half of the more than 6 million heart failure cases in the United States. No currently approved treatments have been clinically proven to significantly improve outcomes specifically for people with HFpEF, the pharma makers said.

"Given the scarcity of treatment options for this debilitating condition, the benefits demonstrated in the EMPEROR-Preserved trial constituted a major clinical breakthrough," Jeff Emmick, M.D., Ph.D., vice president of product development at Lilly, said in a statement. "Together with our Boehringer Ingelheim partners, we look forward to working closely with the FDA through this accelerated process to potentially bring Jardiance to adults with heart failure with preserved ejection fraction as soon as possible."

Results from EMPEROR-Preserved were presented at the European Society of Cardiology Congress 2021 on August 27 and were also published in 

Jardiance demonstrated a 21% relative risk reduction for the composite primary endpoint of cardiovascular death or hospitalization for heart failure.


Jardiance Snags Breakthrough Therapy for Heart Failure with Preserved Injection Fraction

The top medications in the pipeline include a first-in-class treatment for chronic kidney disease (CKD) associated with type 2 diabetes, along with a new oral treatment for migraine headaches and specialty medications for rare liver diseases, according to PBM OptumRx.

Here are the top four drugs in the pipeline in the third quarter, according to OptumRx’s 

) treats patients with chronic kidney disease (CKD) and type 2 diabetes.Diabetes is one of the leading causes of CKD, said OptumRx, noting that there are 26.8 million people diagnosed with diabetes in the United States and about 1 in 3 of them develop some degree of CKD.

“Kerendia is unique in that it was the first drug in the class to be studied in such a robust randomized trial, and there may be some safety benefits versus the older drugs,” Arash Sadeghi, clinical pharmacist of Pipeline and Drug Surveillance at OptumRx, told 

In addition, sodium-glucose cotransporter-2 (SGLT2) inhibitors such as AstraZeneca’s Farxiga (dapagliflozin) are already approved to treat CKD. “So, while Kerendia is unique in mechanism, it will also be competing with drugs such as Farxiga in the CKD population. Compared indirectly, SGLT2 inhibitors such as Farxiga do appear to have more robust data and they are also approved for diabetes, which a major risk factor for CKD,” Sadeghi said.

A barrier to adoption of Kerendia is that other drugs used to treat CKD such as ACE inhibitors are available in generic form and are very inexpensive, OptumRx said, while the wholesale acquisition cost (WAC) for Farxiga is around $6,500 per year.

 is expected to garner FDA approval in the third quarter. It offers an additional oral treatment option for preventing migraine attacks but enters a competitive market, Sadeghi said.

Current oral preventive treatments include beta blockers, antidepressants and anticonvulsants —many of which are available as generic products. In addition, another oral calcitonin gene-related peptide (CGRP) receptor antagonist, Biohaven Pharmaceuticals’ Nurtec ODT (rimegepant), is now approved for migraine treatment and prophylaxis.

“Atogepant is entering a crowded market and will compete with not only Nurtec ODT but with the other current treatment options for migraine prevention,” Sadeghi said. “We lack data comparing atogepant versus historical migraine prophylaxis agents. While it is difficult to compare across clinical trials, atogepant does appear to have similar or incrementally better efficacy than the injectable CGRP antagonists and Nurtec ODT.”

 data from the phase 3 ADVANCE trial evaluating the long-term safety and tolerability of atogepant in several posters at the International Headache Society and the European Headache Federation, on September 8, 2021. The study enrolled 910 patients who completed a 12-week treatment period. Patients were randomized to either placebo or one of three different doses of atogepant.

Investigators found that in all doses, atogepant demonstrated improvements for the primary end point of reduction in mean monthly migraine days. Atogepant was also associated with improvements in migraine-specific quality of life, with improvements seen in the fourth week.

 the first drug approved for the treatment of pruritus in all subtypes of progressive familial intrahepatic cholestasis (PFIC). PFIC is a rare and devastating disorder affecting young children that causes progressive, life-threatening liver disease, according to OptumRx.

While there is a small treatable population of about 600 people with PFIC, there is a high unmet need for effective treatments for the disease, Savitha Vivian, senior vice president of Clinical and Formulary Services at OptumRx, told 

“PFIC is typically unresponsive to conventional treatments that are used off-label, such as ursodeoxycholic acid, antihistamines, or rifampicin. The only proven effective treatments are surgical interventions and transplantation,” Vivian said.

The estimated average cost for Bylvay is $385,000 annually, according to Vivian.

, an oral apical sodium dependent bile acid transporter (ASBT) inhibitor to treat cholestatic pruritus in patients with Alagille syndrome (ALGS) one year of age and older, garnered 

The agency expects to make a formal decision on maralixibat by late September, and it would be the first treatment for the rare liver disease, OptumRx reported. Vivian expects a similar WAC for maralixibat as Bylvay.

“There are high unmet needs for effective treatments for both PFIC and Alagille Syndrome,” OptumRx said. “Bylvay is the first FDA approved treatment for PFIC. Similarly, if approved, maralixibat would be the first approved treatment for Alagille Syndrome. It’s expected that the cost for these drugs will be high given the rarity of the diseases.”

Officials with OptumRx predict four new therapies that are expected to an impact on patients and on the market.

Christine Blank

Articles

Merck Shares Significant Keytruda Breast Cancer Results

Investigational Oral Migraine Treatment Closer to Full FDA Approval

Jardiance Snags Breakthrough Therapy for Heart Failure with Preserved Injection Fraction

OptumRx Reveals Top Drugs in the Pipeline