FDA Updates for Week of June 20, 2022

FDA approves tumor-agnostic cancer therapy, Clovis pulls Rubraca indication, Purdue launches opioid reversal, FDA plans advisory committee meeting for Xphozah, and Manarini and AbbVie submit applications.

Clovis Oncology pulls Rubraca indication in late-stage ovarian cancer.

Clovis Oncology has withdrawn the indication of Rubraca (rucaparib) in the United States as a treatment for patients with BRCA-mutated ovarian cancer after two or more chemotherapies. This withdrawal became effective June 10, 2022, and does not affect other indications for Rubraca.

A recent trial found that in patients with BRCA-mutated epithelial ovarian, Fallopian tubes or primary peritoneal cancer and treated with Rubraca, overall survival was shorter than with those treated with chemotherapy. The results from this trial, ARIEL4, were reported at the 2022 meeting of European Society of Medical Oncology.

Survival in patients treated with Rubraca was 19.6 months compared with 27.1 months for those treated with chemotherapy, with a hazard ratio of 1.550. A hazard ratio above 1 indicates there is harm to the patient.

Clovis has voluntarily requested withdrawal of the treatment indication in Europe.

FDA approves drug combination for tumor agnostic indication.

The FDA has granted accelerated approval for the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) for the treatment of adult and pediatric patients 6 years of age and older with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment. Both therapies were developed and marketed by Novartis.

Tafinlar + Mekinist is the first BRAF/MEK inhibitor to be approved with a tumor-agnostic indication for solid tumors carrying the BRAF V600E mutation. It is the only BRAF/MEK inhibitor approved for use in pediatric patients. Continued approval for this indication is on clinical benefit in a confirmatory trials.

BRAF mutations have been identified as drivers of cancer growth across a wide range of solid tumors, including in rare cancer types that can be challenging to study in Phase III trials and often have limited treatment options. BRAF V600E is the most common type of BRAF mutation, accounting for up to 90% of BRAF-mutant cancers.

Both Tafinlar and Mekinst are approved as a single agent to treat metastatic melanoma, non-small cell lung cancer, and metastatic thyroid cancer.

Purdue launches opioid reversal nalmefene.

Purdue Pharma has introduced nalmefene hydrochloride injection, which is an opioid antagonist indicated for the complete or partial reversal of opioid drug effects, including respiratory depression, induced by either natural or synthetic opioids, and in the management of known or suspected opioid overdose.

Purdue will distribute nalmefene for no profit as part of its commitment to help abate the opioid crisis. This is part of the company’s bankruptcy filing and settlement with 20 states to address the opioid crisis that the company, in part, helped to create. Purdue developed OxyContin (oxycodone). The company’s aggressive marketing, which incorrectly indicated that the pain reliever was not addictive, is seen as a major contributor to the abuse of this and other opioids.

The company and the Sackler family, which owned Purdue Pharma, have agreed to a settlement that would create a trust of about $6 billion to pay for claims from states, hospitals, and those impacted by addition. A judge in March 2022 has approved the settlement.

FDA announces advisory committee meeting for Xphozah.

The FDA’s Cardiovascular and Renal Drugs Advisory Committee meeting is tentatively scheduled for Nov. 16, 2022, to discuss the new drug application for Ardelyx’s Xphozah (tenapanor) for the control of serum phosphorus in adult patients with chronic kidney disease (CKD) who are on dialysis.

As part of its response to Ardelyx’s appeal of the complete response letter received on July 28, 2021, the FDA’s Office of New Drugs stated that additional input from an advisory committee, including the addition of input from expert clinicians who care for patients on dialysis, would be valuable in further considering the clinical meaningfulness of the phosphate lowering effect observed in Ardelyx’s phase 3 clinical program in order to reach a decision on the company's formal dispute resolution request. A response from the OND to Ardelyx’s appeal is expected within thirty calendar days after the conclusion of the Advisory Committee meeting.

Menarini submits NDA elacestrant for advanced breast cancer.

Menarini Group and Radius Health have submitted a new drug application (NDA) to the FDA for elacestrant in patients with ER+/HER2- advanced or metastatic breast cancer. The companies are requesting priority review.

If approved, elacestrant it would be the first oral therapy in a class of medications called selective estrogen receptor degraders (SERDs), which binds to the estrogen receptor and causes it to be downregulated. As a result, SERDs are being studied in breast cancers that have become resistant to aromatase inhibitors or those with tamoxifen resistance.

AstraZeneca’s Faslodex (fulvestrant) was the first SERD to be approved by the FDA in 2017. It is an injection therapy for patients with estrogen receptor positive breast cancer.

AbbVie submits supplemental NDA for Qulipta for chronic migraine.

AbbVie has submitted to the FDA a supplemental new drug application for Qulipta (atogepant) to support the preventive treatment of chronic migraine in adults. If approved, Qulipta would be the first gepant (oral calcitonin gene-related peptide receptor antagonist) approved for the broad indication of the preventive treatment of migraine, including episodic and chronic.

The sNDA submission for Qulipta includes data from the pivotal phase 3 PROGRESS trial in patients with chronic migraine, which supplements the existing data in episodic migraine. People living with chronic migraine experience headaches for 15 or more days per month, which, on at least eight of those days per month, have the features of migraine.

The FDA approved Qulipta in September 2021 for the preventive treatment of episodic migraine in adults.

AbbVie also markets Botox (onabotulinumtoxinA).