FDA broadens the age range of Gardasil 9 to cover individuals 27 through 45 years old

The US Food and Drugs Administration (FDA) extended the use of Merck’s cervical cancer vaccine Gardasil 9 to include men and women aged 27 through 45 years.

"Today's approval represents an important opportunity to help prevent HPV-related diseases and cancers in a broader age range," Peter Marks, MD, Ph.D., director of the FDA's Center for Biologics Evaluation and Research, says in a news release.

"The Centers for Disease Control and Prevention has stated that HPV vaccination prior to becoming infected with the HPV types covered by the vaccine has the potential to prevent more than 90% of these cancers, or 31,200 cases every year, from ever developing," Marks says.

 "The CDC has made increasing HPV vaccination rates a public health priority,” said Jacques Cholat, M.D., president, Merck Vaccines, “and today’s recommendation for GARDASIL 9 is an important milestone in the shared effort to help further reduce the burden of HPV-related cancers and diseases.”

According to CDC, every year about 14 million Americans become infected with HPV; about 12,000 women are diagnosed with, and about 4,000 women die from cervical cancer caused by certain HPV viruses. Additionally, HPV viruses are associated with several other forms of cancer affecting men and women. 

FDA first approved Gardasil in 2006, to prevent certain cancers and diseases caused by HPV Types 6, 11, 16, and 18. Gardasil is no longer available in the US. Gardasil 9 received approval in 2014 for use in girls and women 9 through 26 years of age and boys 9 through 15 years of age for the prevention of the cancers and precancerous lesions of cervix, vulva, vagina, and anus caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.

The approval is based on results of a study involving 3,200 women, aged 27 through 45 years, followed for an average of 3.5 years, Gardasil was 88 percent effective in the prevention of a combined endpoint of persistent infection, genital warts, vulvar and vaginal precancerous lesions, cervical precancerous lesions, and cervical cancer related to HPV types covered by the vaccine.

"The FDA’s approval of Gardasil 9 in women 27 through 45 years of age is based on these results and new data on long-term follow-up from this study," the FDA said.

Similarly, in men aged 27 through 45 years of age, vaccine effectiveness was inferred based on data described above in women, along with efficacy data of Gardasil 9 in younger men aged 16 through 25 years, and immunogenicity data from a clinical trial in which 150 men, 27 through 45 years of age, received a 3-dose regimen of Gardasil over 6 months.

In all the safety and efficacy of Gardasil 9 was evaluated in a total of 13,000 males and females, the most commonly reported side effect being injection site pain, swelling, redness, and headaches.

The FDA granted the Gardasil 9 application priority review status. This program facilitates and expedites the review of medical products that address a serious or life-threatening condition.

Important Information about GARDASIL 9 (Human Papillomavirus 9-Valent Vaccine, Recombinant)

GARDASIL 9 does not eliminate the necessity for women to continue to undergo recommended cervical cancer screening.

Recipients of GARDASIL 9 should not discontinue anal cancer screening if it has been recommended by a health care provider.

GARDASIL 9 has not been demonstrated to protect against disease from vaccine HPV types to which a person has previously been exposed through sexual activity.

GARDASIL 9 has not been demonstrated to protect against diseases due to HPV types other than 6, 11, 16, 18, 31, 33, 45, 52, and 58.

GARDASIL 9 is not a treatment for external genital lesions; cervical, vulvar, vaginal, and anal cancers; or cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), or anal intraepithelial neoplasia (AIN).

Not all vulvar, vaginal, and anal cancers are caused by HPV, and GARDASIL 9 protects only against those vulvar, vaginal, and anal cancers caused by HPV 16, 18, 31, 33, 45, 52 and 58.

Vaccination with GARDASIL 9 may not result in protection in all vaccine recipients.

FDA press release

Merck news release

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KEYTRUDA gains FDA approval for treatment of recurrent or metastatic cervical cancer

The U.S. Food and Drug Administration (FDA) has approved Merck’s pembrolizumab (KEYTRUDA®), for the treatment of patients with recurrent or metastatic cervical cancer whose disease had worsened on or after chemotherapy and whose tumors express programmed cell death ligand 1 (PD-L1), as determined by an FDA approved test.

The US FDA has approved the Dako PD-L1 IHC 22C3 pharmDx assay for expanded use as a companion diagnostic test for Keytruda for cervical cancer.

The approval comes in way ahead of the previously decided date of June 28. Furthermore, the drug is approved under the FDA’s accelerated approval regulations based on tumor response rate and durability of response.

Continued approval in future will be based upon verification and description of clinical benefit in the ongoing trials ahead.

The accelerated approval was based on results of ongoing KEYNOTE-158, a multi-center, non-randomized, open-label, multi-cohort trial (NCT02628067). The trial enrolled patients with multiple types of advanced solid tumor, who have not responded to usual chemotherapy or are intolerant to it.

Patients with autoimmune diseases or requiring immunosuppression were excluded from the trial.

The patients received KEYTRUDA intravenously at a dose of 200 mg every three weeks until unacceptable toxicity or documented disease progression or for 24 months in patients without disease progression.

Among the 98 patients with advanced cervical cancer, 77 (79%) had tumors that expressed PD-L1 with a Combined Positive Score (CPS) ≥1 and have received at least one line of chemotherapy in the metastatic setting.

The objective response rate in these 77 patients was 14.3 percent, with a complete response in 2 patients (2.6%) and partial response in 9 patients (11.7%).

Ninety-one percent of patients experienced duration of response exceeding 6 months or longer. Eight patients discontinued the drug because of serious side effects like anemia, fistula, hemorrhage, and infection.

The other common side effects of KEYTRUDA are fatigue, musculoskeletal pain, diarrhea, pain and abdominal pain and decreased appetite (21%).

 No responses were observed in patients whose tumors did not have the PD-L1 expression (CPS<1).

KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells. This increases the ability of the body's immune system to help detect and fight tumor cells.

Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories said, “KEYTRUDA is now the first anti-PD-1 therapy approved for the treatment of advanced cervical cancer, providing an important new second-line option for certain patients with this disease. This approval also marks the first indication for KEYTRUDA in gynecologic cancer and reflects our ongoing commitment to bring forward innovative treatment options across a broad range of cancers, including cancers that disproportionately affect women,” in a news release.

KEYTRUDA has already been approved by FDA for treatment of melanoma, head and neck cancer, lung cancer, urothelial cancer, and gastric cancer.

Merck News Release 

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FDA approves first cancer treatment drug based on tumor biomarker, instead of tumor origin.

courtesy: Merck 

In an important announcement, The U.S. Food and Drug Administration (FDA) granted accelerated approval to Merck’s Keytruda (pembrolizumab) for treatment in patients whose cancers have a specific genetic feature (biomarker).

This is the first time the agency has approved a cancer treatment based on a common biomarker rather than the location in the body where the tumor originated.

Keytruda (pembrolizumab) is indicated for the treatment of adult and pediatric patients who have unresectable or metastatic solid tumors that have been identified as having a biomarker referred to as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).

Tumors with these biomarkers are most commonly found in colorectal, endometrial and gastrointestinal cancers, but also less commonly appear in cancers arising in the breast, prostate, bladder, thyroid gland and other places.

“This is an important first for the cancer community,” said Richard Pazdur, M.D., acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research and director of the FDA’s Oncology Center of Excellence. “Until now, the FDA has approved cancer treatments based on where in the body the cancer started—for example, lung or breast cancers. We have now approved a drug based on a tumor’s biomarker without regard to the tumor’s original location.”

Keytruda works by blocking the cellular pathway known as PD-1/PD-L1 (proteins found on the body’s immune cells and some cancer cells). Keytruda is currently used in patients with metastatic melanoma, metastatic non-small cell lung cancer, recurrent or metastatic head and neck cancer, refractory classical Hodgkin lymphoma, and urothelial carcinoma.

The FDA approval comes in wake of results of 5 clinical trial involving 149 patients with 15 different cancer types. The common cancers were endometrial, gastrointestinal and colorectal.

Nearly 40% of patients in this trial responded well to the treatment with 78% of those were symptom free for more than 6 months.

Common side effects of Keytruda include fatigue, itchy skin (pruritus), diarrhea, decreased appetite, rash, fever (pyrexia), cough, difficulty breathing (dyspnea), musculoskeletal pain, constipation and nausea.

 Keytruda can cause serious conditions known as immune-mediated side effects, including inflammation of healthy organs such as the lungs (pneumonitis), colon (colitis), liver (hepatitis), endocrine glands (endocrinopathies) and kidneys (nephritis).

The FDA press release can be accessed here.