Kristen Coppock

Officials with the FDA have conditionally approved crofelemer delayed-release oral tablets (Canalevia-CA1; Jaguar Animal Health) for the treatment of chemotherapy-induced diarrhea in dogs. This novel drug is the first treatment to be approved for this condition.

"Diarrhea is a common side effect of chemotherapy in dogs, which can be so severe that cancer treatment must be halted. Chemotherapy drugs often have potential side effects, but, unlike in human medicine where patients may be willing to tolerate some discomfort in exchange for a potential cure, the primary purpose of cancer treatment in dogs and other pets is to extend survival without sacrificing quality of life and comfort," said Steven M. Solomon, DVM, MPH, director of the FDA's Center for Veterinary Medicine, in a prepared statement. "This new medication provides veterinarians and dog owners with another tool to help control the side effects of chemotherapy for dogs undergoing such treatment."

According to Jaguar Animal Health, crofelemer is a plant-based medicine extracted and purified from the red bark sap—or “dragon's blood"—of the medicinal 

 tree in the Amazon Rainforest. The company’s subsidiary, Napo Pharmaceuticals, has established a sustainable harvesting program, under fair trade practices, for crofelemer to ensure a high degree of quality, ecological integrity, and support for Indigenous communities.

Crofelemer is approved for human use to treat noninfectious diarrhea in adults with HIV/AIDS who take antiretroviral therapy. In humans, crofelemer functions by inhibiting the secretion of chloride ions and water by intestinal epithelial cells, thereby normalizing the gastrointestinal tract. According to the FDA, it is thought that the drug functions similarly in dogs.

Crofelemer delayed-release tablets for dogs are available only by prescription and can be administered at home. This therapy received conditional approval through the FDA’s Minor Use/Minor Species pathway, which is an option for drugs intended for minor uses in major species such as dogs, cats, horses, cattle, pigs, turkeys and chickens; or for minor species. According to the FDA, an estimated 1% of dogs in the United States receive a diagnosis of malignant neoplasia (cancer) per year, and not all dogs that receive treatment suffer from chemotherapy-induced diarrhea. Therefore, the agency estimates the rate of occurrence of chemotherapy-induced diarrhea in dogs in the US to be fewer than 70,000 dogs, which qualifies it as a minor use in a major species.

In addition, the conditional approval allows an animal drug sponsor to legally market its product after demonstrating that the drug is safe and manufactured in accordance with full approval standards and that there is a reasonable expectation of the drug's effectiveness. The initial conditional approval is valid for 1 year with the potential for 4 annual renewals. During this time, the animal drug sponsor must demonstrate active progress toward proving substantial evidence of effectiveness for full approval. The animal drug sponsor has 5 years to obtain full approval after receiving conditional approval, or it will no longer be allowed to be marketed.

The reasonable expectation of effectiveness of crofelemer delayed-release tablets was established in a study with 24 dogs (12 treated and 12 control). A dog was considered a treatment success if its diarrhea resolved and didn't recur during the 3-day study. Resolution of diarrhea was defined as a fecal score of 1 (well-formed stool) or 2 (soft or very soft, moist stool that doesn't have a clear shape). On the third day, 75% of dogs in the treated group were treatment successes compared to 25% of dogs in the control group. Additionally, diarrhea had resolved by 48 hours in 33% of dogs in the treated group compared to none of the dogs in the control group.

Some of the most common adverse effects across the laboratory studies and field studies were abnormal feces (soft, watery, mucoid, discolored feces), decreased appetite and activity, and vomiting.

 According to Jaguar Animal Health, managing adverse effects is imperative to maintaining successful cancer treatment. However, more than half of the US veterinarians who responded to a recent survey sponsored by the company reported that chemotherapy-induced diarrhea interferes with their patient's chemotherapy treatment plan.

FDA Conditionally Approves First Oral Tablet to Treat Chemotherapy-Induced Diarrhea in Dogs. FDA. December 21, 2021. Accessed December 21, 2021. 

https://www.fda.gov/news-events/press-announcements/fda-conditionally-approves-first-oral-tablet-treat-chemotherapy-induced-diarrhea-dogs

Jaguar Health announces FDA Conditional Approval of Canalevia-CA1 (crofelemer), the first and only treatment for chemotherapy-induced diarrhea (CID) in dogs to receive any type of approval from FDA. Jaguar Animal Health. December 21, 2021. Accessed December 21, 2021. 

https://jaguarhealth.gcs-web.com/news-releases/news-release-details/jaguar-health-announces-fda-conditional-approval-canalevia-ca1

Articles

The prescription-only crofelemer delayed-release tablets were developed using a sustainable, plant-based formula.

First Oral Tablet for Chemotherapy-induced Diarrhea in Dogs Receives Conditional FDA Approval

oral oncolytics has become increasingly prevalent in cancer care with their use accelerated by the COVID-19 pandemic.

 Adherence to these medications, however, can be challenging for patients.

In a session of the virtual American Society of Health-System Pharmacists (ASHP) Specialty Pharmacy Conference, presenter Eve Segal, PharmD, BCOP, lead clinical pharmacist, University of Washington Medical Center/Seattle Cancer Care Alliance, discussed advantages of oral oncolytics as well as a need for pharmacists to understand barriers to adherence faced by patients who are prescribed these medications. Segal also offered strategies for improving adherence for patients taking these medications.

“Oral oncolytics really have solidified their place in cancer treatment. The oral route has many advantages in cancer management. In some cases, the oral route is actually preferred [to other forms of medication],” Segal said during the ASHP session.

According to Segal, oral oncolytics offer more convenience and improved quality of life for patients than other forms of therapy. She noted less interference with work and social activities, avoiding painful injections and prolonged time with infusions, as well as allowing patients to take more ownership of their therapy with self-administration. Additionally, in some cases, patients taking oral oncolytics may experience prolonged drug exposure and may have access to a more effective delivery option.

Although adherence to medication leads to better control of the disease, rates of adherence vary widely. A review of literature showed that adherence rates with oral antineoplastic therapies range between 46% and 100%, with differences in study results based on patient sample, medication type, measure of assessment, adherence calculation, and when follow-up occurred.

 Segal said barriers exist that prevent many patients from taking their oral oncolytics. She cited common barriers

cost, regimen complexity, adverse events, poor access to medication

poor understanding, lack of belief in efficacy, lack of understanding for therapy's purpose, inability to see benefits

poor communication with care team, language deficits, poor literacy, lack of support system, cultural or religious beliefs

Direct and indirect methods can help improve adherence. Although expensive and impractical, smart pill bottles and smart caps can assist many patients, for example. Self-reporting by patients, pill counts, and pharmacy claims data are examples of indirect support for adherence; however, these methods do not prove that a patient has taken a medication.

“Each method has its own advantages and disadvantages,” Segal said. “Keep in mind that there is no gold standard to assessing and evaluating adherence.”

By working with an oncology care team, pharmacists have opportunities to help improve care for patients with cancer who are taking oral oncolytic agents.

 Segal suggested using a combination of patient education and behavioral intervention, and routinely following up with patients to combat nonadherence. These strategies may include informational handouts that use plain language; calendars or other visual reminders; reviewing the refill process and confirming that a patient understands it; ensuring a patient is scheduled for a follow-up visit to assess adherence and potential toxicities to treatments; discussing medication cost; use of pill boxes; and smartphone apps that remind patients to take their medications. Segal said a pharmacist’s approach should be customized to individual patients based on what works best for them.

Overall, patient education is key, Segal said, noting that there is no clear, best way to educate patients, but the information provided should be consistent.

“Patients should also know how to obtain their medication, the role of the specialty pharmacy, and [about] financial assistance,” she said.

Castro C, Manoogian A. COVID-19 and the impact on oral oncolytics: a specialty pharmacy perspective. 

. 2020;2(4):16-17. https://www.pharmacytimes.com/view/ covid-19-and-the-impact-on-oral-oncolytics-a-specialty-pharmacy-perspective

Segal E. Improving adherence to patients receiving oral oncolytics: a review of current strategies. Presented at: American Society of Health-System Pharmacists Specialty Pharmacy Conference; virtual. June 14-16, 2021.

Segal EM, Flood MR, Mancini RS, et al. Oral chemotherapy food and drug interactions: a comprehensive review of the literature. 

. 2014;10(4):e255-268. doi:10.1200/JOP.2013.001183

Greer JA, Amoyal N, Nisotel L, et al. A systematic review of adherence to oral antineoplastic therapies. 

. 2016;21(3):354-376. doi:10.1634/ theoncologist.2015-0405

Mackler E, Segal EM, Muluneh B, Jeffers K, Carmichael J. 2018 Hematology/ Oncology Pharmacist Association best practices for the management of oral oncolytic therapy: pharmacy practice standard. 

. 2019;15(4):e346-e355. doi:10.1200/ JOP.18.00581

Multiple strategies can be used to create an individualized approach to therapies and removing barriers for patients with cancer.

Improving Adherence to Oral Oncolytics

New data demonstrate capmatinib (Tabrecta; Novartis) as a promising treatment option for patients with 

ex14) non–small cell lung cancer (NSCLC).

A kinase inhibitor, capmatinib is approved by the FDA for the treatment of adult patients with metastatic NSCLC whose tumors have a mutation that leads to 

 exon 14 skipping. This approval was based on the phase 2 GEOMETRY (NCT02414139) mono-1 study. Results of the study were presented at the virtual 2021 American Society of Clinical Oncology Annual Conference.

The findings include data from the GEOMETRY study's new cohort 7 and updates some previously reported analyses.

 According to investigators, capmatinib achieved overall response rate (ORR) of 65.6% (95% CI, 46.8-81.4) in the first-line setting for cohort 7, and 67.9% ORR (95% CI, 47.6-84.1) in cohort 5b. In the second-line setting, 51.6% ORR was achieved in the new expansion cohort.

Capmatinib also demonstrated a median duration of response (DOR) of 12.6 months (95% CI, 5.6-not estimable [NE]) among treatment-naive patients in cohort 5b. DOR for treatment-naive patients in cohort 7 is NE. Among previously treated patients, DORs of 9.7 months (95% CI, 5.61-3.0) and 8.4 months (95% CI, 4.2NE) were found in cohort 4 and cohort 6, respectively.

Additionally, the study found a mature median overall survival (OS) rate of 20.8 months (95% CI, 12.42-not estimable [NE]) for treatment-naive patients in cohort 5b, and 13.6 months (95% CI, 8.61-22.24) in previously treated patients in cohort 4. Median OS for cohorts 6 and 7 are not yet reached, according to the authors.

ex14 who received capmatinib 400 mg twice daily were analyzed. Although data for cohort 7 are still immature, the authors announced that median progression-free survival was 10.8 months (95% CI, 6.87-NE).

"This new analysis further supports [capmatinib] as a cornerstone targeted treatment for [patients with] 

ex14 NSCLC and highlights the importance of biomarker testing," Juergen Wolf, MD, from the Center for Integrated Oncology, University Hospital of Cologne, Germany, and lead investigator of the GEOMETRY study, said in a press release.

 "The impressive overall survival outcome and confirmed outstanding response in the first-line setting will help oncologists decide upon a therapeutic option for patients."

According to investigators, the safety profile remained unchanged across all GEOMETRY study cohorts (N=373), with 98.4% of patients reporting at least 1 adverse event (AE) (68.6% grade 3/4) regardless of causality, and 50.9% of patients reporting at least 1 serious AE. In 16.1% of patients, AEs leading to discontinuation (10.5% grade 3/4) were reported.

Serious AEs reported in patients taking capmatinib include lung or breathing problems, liver problems, and risk of photosensitivity. The most commonly reported AEs (≥ 20% all grades) include swelling of the hands or feet, nausea, tiredness, weakness, vomiting, loss of appetite, and changes in certain blood tests.

1. Wolf J, Garon EB, Groen HJM, et al. Capmatinib in 

 exon 14-mutated, advanced NSCLC: updated results from the GEOMETRY mono-1 study

 2021;39(suppl 15; abstr 9020). doi:10.1200/JCO.2021.39.15_suppl.9020

2. Tabrecta (capmatinib) tablets. Prescribing information. Novartis; 2020. Accessed June 8, 2021. 

https://www.novartis.us/sites/www.novartis.us/files/tabrecta.pdf

3. Novartis announces Tabrecta first published overall survival and updated overall response data in patients with 

ex14 metastatic NSCLC. News release. Novartis. June 4, 2021. Accessed June 9, 2021. 

https://www.novartis.com/news/media-releases/novartis-announces-tabrecta-first-published-overall-survival-and-updated-overall-response-data-patients-metex14-metastatic-nsclc

The kinase inhibitor is a promising treatment option for patients with MET exon 14 skipping mutation non–small cell lung cancer.

New Data Show Promise for Patient Outcomes With Capmatinib

The FDA’s Vaccines and Related Biological Products Advisory Committee has recommended an emergency use authorization (EUA) for Johnson & Johnson’s single-dose COVID-19 vaccine. The vaccine under review was developed by the company’s Janssen division.

In voting in favor of the recommendation, 22 committee members unanimously agreed that the benefits of the Janssen COVID-19 vaccine outweigh its risks in individuals age 18 years and older, based on the totality of scientific evidence currently available.

If granted an EUA, the Janssen COVID-19 vaccine would be the third approved vaccine for COVID-19, in the United States following the EUA for 

 vaccine on December 12, 2020, and the EUA for 

In his comments to the committee following the vote, Jay Portnoy, MD, said he believes the Janssen COVID-19 vaccine is as safe and effective as other vaccines currently approved by the FDA, such as influenza vaccines.

“The main thing to keep in mind is that we’re dealing with a pandemic right now….There is an urgency to get this done. We’re in a race between the virus mutating, new variants coming out that can cause further disease, and stopping it. The fewer people who are infected with the virus the less opportunity it has to emerge as a more virulent strain,” said Portnoy.

 provides strong protection against severe disease and may reduce transmission of the virus. It is a replication-incompetent adenovirus type 26 vectored vaccine with a stabilized variant of the SARS-CoV-2 S protein and is approved for adults 18 years of age and older.

“I do believe its evidence supports the safety and effectiveness,” Portnoy said.

The single-dose approach would enable vaccination of hard-to-reach populations, such as homeless individuals and those in rural communities. The vaccine is also easier to store, remaining stable at normal refrigeration temperatures for up to 3 months.

According to a joint statement by Janet Woodcock, MD, the FDA's acting commissioner; and Peter Marks, MD, PhD, director of the agency's Center for Biologics Evaluation and Research, issued following the advisory committee's meeting earlier today, the FDA will rapidly work toward finalization and issuance of an EUA. "The agency has also notified our federal partners involved in vaccine allocation and distribution so they can execute their plans for timely vaccine distribution," said Woodcock and Marks in their statement.

Vaccine and Related Biological Products Advisory Committee—2/26/21. FDA. Accessed February 26, 2021. https://www.youtube.com/watch?v=Qd7mlCD-rEA&feature=youtu.be

FDA Analysis Finds Johnson & Johnson Single Shot COVID-19 Vaccine Protects Against Severe Illness, May Reduce Transmission. 

; February 24, 2021. Accessed February 26, 2021. 

https://www.pharmacytimes.com/news/fda-analysis-finds-johnson--johnson-single-shot-covid-19-vaccine-protects-against-severe-illness-may-reduce-transmission

FDA Statement on Vaccines and Related Biological Products Advisory Committee Meeting [news release]. Silver Spring, MD; February 26, 2021: FDA. Accessed February 26, 2021. https://www.fda.gov/news-events/press-announcements/fda-statement-vaccines-and-related-biological-products-advisory-committee-meeting-1

In voting in favor of the recommendation, 22 committee members unanimously agreed that the benefits of the Johnson & Johnson COVID-19 vaccine outweigh its risks.

FDA Committee Votes to Recommend New Johnson & Johnson COVID-19 Vaccine for EUA

Officials with the FDA have approved the first gene therapy for treating children less than 2 years of age with spinal muscular atrophy (SMA).

The drug, onasemnogene abeparvovec-xioi (Zolgensma, AveXis), is an adeno-associated virus vector-based gene therapy that targets the cause of SMA, a leading genetic cause of infant mortality.

The application for approval submitted by AveXis, a Novartis company, was granted the FDA's Fast Track, Breakthrough Therapy, and Priority Review designations, as well as an Orphan Drug designation. In addition, the FDA awarded AveXis a rare pediatric priority review voucher, under a program intended to encourage the development of new drugs and biological products for the prevention and treatment of certain rare pediatric diseases, according to the agency.

“Today’s approval marks another milestone in the transformational power of gene and cell therapies to treat a wide range of diseases,” said Acting FDA Commissioner Ned Sharpless, MD, in a prepared statement. “With each new approval, we see this exciting area of science continue to move beyond the concept phase into reality. The potential for gene therapy products to change the lives of those patients who may have faced a terminal condition, or worse, death, provides hope for the future. The FDA will continue to support the progress in this field by helping to expedite the development of products for unmet medical needs through the use of review pathways designed to advance innovative, safe and effective treatment options.”

Children with SMA have problems holding their head up, swallowing and breathing. These symptoms may be present at birth or may present by the age of 6 months.

“Children with SMA experience difficulty performing essential functions of life. Most children with this disease do not survive past early childhood due to respiratory failure” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. “Patients with SMA now have another treatment option to minimize the progression of SMA and improve survival. This approval demonstrates the continued momentum of this promising new area of medicine and the FDA’s commitment to supporting and helping expedite the development of these products.”

The safety and effectiveness of onasemnogene abeparvovec-xioi is based on an ongoing clinical trial and a completed clinical trial involving a total of 36 pediatric patients with infantile-onset SMA between the ages of approximately 2 weeks and 8 months at study entry, according to the FDA. The primary evidence of effectiveness is based on results from the 21 patients treated with Zolgensma in the ongoing clinical trial.

In this trial, there are 19 remaining patients, who range in age from 9.4 to 18.5 months; 13 of these 19 patients are at least 14 months of age. Compared to the natural history of patients with infantile-onset SMA, patients treated with Zolgensma also demonstrated significant improvement in their ability to reach developmental motor milestones (e.g., head control and the ability to sit without support).

"A diagnosis of SMA is devastating, leaving untreated babies who have the most severe form with painfully short, highly medicalized lives, during which they are unable to lift their heads, sit or roll, have difficulty swallowing and breathing and need 24-hour care," said Jerry Mendell, M.D., principal investigator at the Center for Gene Therapy at The Abigail Wexner Research Institute of Nationwide Children's Hospital in Columbus, OH, in a prepared statement. "In the START clinical trial we conducted with Zolgensma, all children were alive at the conclusion of the study and many were able to sit, roll, crawl, play and some could walk. This level of efficacy, delivered as a single, one-time therapy, is truly remarkable and provides a level of unprecedented hope for families battling SMA Type 1. We now have data 4 years out from the trial, and we see the durability of this gene therapy."

Vas Narasimhan, CEO of Novartis, said the approval of onasemnogene abeparvovec-xioi serves as a testament to the “transformational impact” that gene therapies can have in treating life-threatening genetic diseases, such as SMA.

"We believe Zolgensma could create a lifetime of possibilities for the children and families impacted by this devastating condition," Narasimhan added, in a prepared statement.

According to the FDA, a 1-time intravenous administration of onasemnogene abeparvovec-xioi results in expression of the SMN protein in a child’s motor neurons, which improves muscle movement and function, and survival of a child with SMA.

Dosing is determined based on the weight of the patient.

The most common adverse effects of onasemnogene abeparvovec-xioi are elevated liver enzymes and vomiting. The drug has a boxed warning that acute serious liver injury can occur, and patients with pre-existing liver impairment may be at higher risk of experiencing serious liver injury.

Clinical examination and laboratory tests to assess liver function should be completed prior to treatment with onasemnogene abeparvovec-xioi, and patients’ liver function should be monitored for at least 3 months after this drug is administered.

Certain vaccines are contraindicated for patients on a substantially immunosuppressive steroid dose. Health care professionals should offer consultation for determining potentially needed adjustments to patients’ vaccination schedules in order to accommodate concomitant corticosteroid administration. 

This article was originally published on 

		FDA approves innovative gene therapy to treat pediatric patients with spinal muscular atrophy, a rare disease and leading genetic cause of infant mortality [news release]. Silver Spring, MD; May 24, 2019: FDA website. https://www.fda.gov/news-events/press-announcements/fda-approves-innovative-gene-therapy-treat-pediatric-patients-spinal-muscular-atrophy-rare-disease. Accessed May 24, 2019.

		AveXis receives FDA approval for Zolgensma®, the first and only gene therapy for pediatric patients with spinal muscular atrophy (SMA) [news release]. Basel, Switzerland; May 24, 2019: AveXis website. http://investors.avexis.com/phoenix.zhtml?c=254285&p=irol-newsArticle&ID=2399684. Accessed May 24, 2019.

FDA Oks Gene Therapy for Children with Spinal Muscular Atrophy

A federal appropriations bill will not include a bipartisan provision that would have required drug manufacturers to be more transparent with costs to consumers after it was blocked by House Republicans.

 Jointly sponsored by Senator Dick Durbin, D-Illinois, and Senator Chuck Grassley, R-Iowa, the provision would have required list prices included in direct-to-consumer television advertising.

The provision was part of the Trump administration’s drug pricing blueprint, and had received support from both political parties.

 Both Durbin and Grassley took to social media after the provision failed to move forward, to comment on the outcome, expressing disappointment with fellow members of Congress.

In a series of tweets, Durbin said the provision was widely supported by lawmakers, as well as national health organizations, including the American Medical Association, and health insurers. According to the senator, the measure was opposed only by drug manufacturers and members of Congress who support those companies.

The #1 driver for increases in premiums are Rx drugs & TV drug ads inflate drug spending without telling patients how much it costs. It's disappointing this measure was pulled at the last minute by House GOP. We need transparency & it's time to put consumers ahead of Big Pharma.

— Senator Dick Durbin (@SenatorDurbin) 

, American Medical Association, health insurance plans, 76% of Americans, Pres Trump & HHS. The only group who opposed it? Big Pharma & their Representatives in Congress: 

 Also on Twitter, Grassley indicated members of Congress wee bowing to drug manufacturers at the expense of consumers. “It is embarrassing," he said. 

Hearing rumors my bipartisan Durbin/Grassley legis to make drug companies list prices on TV ads is out of spending bill It is EMBARRASSING to bow to BIG PHARMA at expense of consumers Policy is supported by Pres Trump+AARP+Dem&GOP Sens If we can agree why are lobbyists fighting?

Industry officials did indeed take issue with the amendment; the Pharmaceutical Research and Manufacturers of America (PhRMA) spoke out against the proposal in its July comments to HHS on the administration’s drug pricing blueprint, saying “FDA should not pursue any required disclose of list prices in direct-to-consumer pharmaceutical advertising. Such a requirement could confuse patients since the list price often does not represent what they would actually be required to pay.”

Exclusion of the amendment appears to counter public sentiment; a recent poll from the Kaiser Family Foundation found that nearly 76% of the public supports the inclusion of list prices in television ads.

The Campaign for Sustainable Rx Pricing, a nonprofit, nonpartisan coalition of health care professionals, including pharmacists, called the exclusion of the provision a “major opportunity” missed to help lower drug prices.

This bill abandons the real bipartisan progress the Senate and the Trump Administration made to hold Big Pharma accountable for out-of-control drug prices and give patients the information they need to make smart decisions about their health care,” said campaign officials, in a prepared statement.

 “Requiring drug makers to disclose prices in direct-to-consumer advertising is not only strongly supported by the American public, bipartisan Members of Congress and the Administration, it’s simply the right thing to do. Just as patients need to know about the possible side effects of a drug, they also need to know how much it costs and if there are more affordable treatments available.

In a prepared statement, the organization also applauded the efforts of Durbin and Grassley to address the issue of drug prices and promoting transparency.

Mulero A. Lawmakers Halt Push for Drug Prices in TV Ads. 

 website. Published September 17, 2018. Accessed September 2018.

RFI Comments on HHS Blueprint to Lower Drug Prices and Reduce Out-of-Pocket Costs. PhRMA website. Published July 16, 2018. Accessed September 2018.

Kaiser Health Tracking Poll—June 2018: Campaigns, Pre-Existing Conditions, and Prescription Drug Ads. Kaiser Family Foundation website. Published June 27, 2018. Accessed September 2018

CSRxP statement on exclusion of brig pharma accountability amendment in appropriations bill. Campaign for Sustainable Rx Pricing website. Published September 13, 2018. Accessed September 2018.

A federal appropriations bill will not include bipartisan provision that would have required drug manufacturers to be more transparent with costs to consumers after it was blocked by House Republicans.