Merck’s Chronic Cough Med Gefapixant Receives A Red Flag From the FDA, Requests For More Data

On 24th January 2022, Merck & Co. announced FDA rejection for its New Drug Application (NDA) of Gefapixant (experimental drug) for unexplained or chronic cough. FDA asked for additional information on the drug, related only to the effectiveness and not safety. The drug is an oral selective, non-narcotic, P2X3 receptor antagonist. With this disapproval in hand, there are currently no FDA-approved drugs for the treatment of unexplained/chronic/refractory cough. Unexplained chronic cough is a cough lasting at least 8 weeks with no etiology identified despite a thorough investigation.  Initially, on March 1, 2021, FDA had accepted the first NDA for Gefapixant which was based on results from a first companion Phase III, COUGH-1 and COUGH-2 studies, where a total of 2,044 patients participated in clinical trials. The treatment period for COUGH-1 was 12 weeks with an additional 40-week extension period, whereas for COUGH-2, there was a 24-week treatment period further with a 28-week extension period. 

Although Merck received a turndown from FDA, Japan’s health regulators have absolutely agreed on treating refractory or unexplained chronic cough with the same drug. They approved the drug last week and it will be marketed by the name – Lyfnua in Japan.

FDA’s decision might impact the approval of Gefapixant now for several months, but that could be much relieving for the rival drug from Canada’s clinical-stage pharmaceutical company – Bellus Health Inc. chronic cough treatment candidate, BLU-5937. Merck is adamant about providing efficacy results to the FDA in the coming future and stated that it would meet the agency in order to follow up with the next steps for the advancement of the drug. 

FDA Disapproves Pfizer and OPKO’s Growth Hormone Deficiency Drug Somatrogon

USFDA turns down the once-weekly human growth hormone Somatrogon co-developed by OPKO Health Inc. and Pfizer for Growth Hormone Deficiency (GHD) treatment in pediatric patients. Both the companies have not yet mentioned the reasons for the healthcare regulatory agency’s disapproval. Pfizer has stated that it is currently evaluating FDA’s comments and will work with the agency for the future directions in the right way.

Growth Hormone Deficiency is a rare genetic disorder caused by mutations in genes. In this condition, the pituitary gland doesn’t produce a sufficient amount of growth hormone – somatropin, in order to stimulate the growth of the body. It can be distinguished by several factors such as abnormally short height, younger-looking face, delayed puberty, etc. It affects almost 4000-10,000 children worldwide. Pfizer and OPKO’s cumulative Somatrogon clinical trial results were based on a global Phase III trial data with 224 previously untreated children as participants. In this study, a comparison was formulated between once-weekly Somatrogon and previously approved Genotropin (Pfizer) as a once-daily treatment.

Pfizer and OPKO partnered in the year 2014 for the development of Somatrogon, they are currently in competition with Ascendis Pharma’s Skytrofa (FDA approved) for treating children with growth failure from inadequate secretion of endogenous growth hormone (GH) aged 1 year and above. Both the pharmaceuticals are seeking the drug’s regulatory approval throughout the world, where it has been approved in Canada and Australia. Just last week, Somatrogon got approval in Japan and will be sold under the name – Ngenla. Also, the European Commission will provide their approval later this year.

Gilead Withdraws the Use of Zyedelig Drug for Two Cancer Accelerated Approvals Due to Change in Lymphoma Landscape

After failing to complete the confirmatory trials required, Gilead Sciences Inc informed the U.S. Food and Medicine Administration of its decision to voluntarily withdraw the use of its drug Zydelig for two kinds of cancer- Follicular Lymphoma and Small Lymphocytic Leukemia. In 2014, FDA granted Zydelig, expedited approval to treat Relapsed Follicular B-cell Non-Hodgkin Lymphoma (NHL) and Relapsed Small Lymphocytic Leukemia (SLL), as well as relapsed Chronic Lymphocytic Leukemia (CLL).

Enrollment in the confirmatory study for both Follicular Lymphoma and Small Lymphocytic Leukemia has been difficult. However, the approval came with a boxed warning about the possibility of severe and potentially fatal toxicities.

The results accumulated were based on Phase II Data showing cancer responses, Gilead received accelerated clearances for Follicular Lymphoma and Small Lymphocytic Leukemia. Drugs that came after it, on the other hand, have more developed clinical efficacy data. After reports of many deaths in its clinical programs in 2016, Zydelig’s Rituxan combo trials were halted early. Zydelig’s sales never recovered due to the safety concern, with global sales of only $50 million in the first nine months of 2021.

T.G. Therapeutics’ Ukoniq, a potentially safer PI3K option than Zydelig, has also received FDA approval in the late-line setting and is undertaking clinical trials to move earlier in the therapy sequence. In addition, because of an FDA nod in 2016 based on disease progression data, AbbVie and Johnson & Johnson’s BTK inhibitor, Imbruvica, has been able to treat newly diagnosed CLL and SLL patients.

Lantern Pharma’s LP-184 Received Orphan Drug Designation For the Treatment of Atypical Teratoid Rhabdoid Tumor (ATRT)

Lantern Pharma is a clinical-stage oncology company that develops tailored cancer medicines using AI, Machine Learning, and genomics. Lantern creates treatments by combining genetic data, computational biology modeling, and artificial intelligence tools to better understand the probable mechanism of action underlying drug-tumor response and identify the patient groups most likely to react to the therapy. The company’s therapeutic candidate LP-184 for the treatment of ATRT (Atypical Teratoid Rhabdoid Tumor) in children, has been granted both Rare Pediatric Disease Designation and Orphan Drug Designation by the USFDA.

LP-184 is being studied as a possible novel treatment for a variety of genetically determined solid tumors, including Pancreatic Cancer, GBM (Glioblastoma Multiforme), and ATRT (Atypical Teratoid Rhabdoid Tumor).

“Historical techniques in pediatric ATRT treatment, such as surgery, radiation, and chemotherapy, have mostly had adverse long-term outcomes for children, and new choices are desperately needed”, stated Kishor Bhatia, Ph.D., Lantern Pharma’s chief scientific officer. Additionally, he said, “LP-184 has the potential to become a crucial part of the armamentarium of approved therapy options specifically for these individuals, based on both in-silico and in-vivo findings.” 

The FDA’s designation as a Rare Pediatric Disease highlights the importance of Lantern’s growing focus on pediatric cancer indications and marks another key milestone for the LP-184 program. ATRT tumors are classified as Grade IV tumors by the National Cancer Institute, indicating that they are malignant, aggressive, and fast-growing. ATRTs are highly aggressive central nervous system tumors in children. Inactivating bi-allelic mutations in SMARCB1 (also known as INI1) or SMARCA4 is the underlying genetic cause. Changes in the SMARCB1 gene are responsible for nearly 90% of pediatric ATRTs.

The FDA designates severe and life-threatening disorders in children aged 18 years and younger that afflict fewer than 200,000 people in the United States as rare pediatric diseases. 

The FDA Has Extended its Approval to Patients Outside of the Hospitals as the Oral Version of Gilead’s Veklury Heads to Trial

Veklury, the first FDA-approved COVID-19 treatment, from Gilead Sciences, has expanded its reach to patients outside of the hospital at a time when effective anti-omicron therapies are in high demand. The FDA approved the drug last Friday to treat adults and adolescents who are at high risk of developing severe COVID-19 illness. Previously, the drug was only available to hospitalized patients.

Veklury had been given to more than 10 million patients around the world at the time, and it was given to 3 out of every 5 patients hospitalized in the United States.

The accelerated approval adds a much-needed new antiviral option to the antiviral arsenal for outpatients. Existing antibodies from Eli Lilly and Regeneron appear to have lost some of their potency against the rapidly spreading omicron variant, leaving few options for the many mild COVID-19 cases treated outside of a hospital.

Furthermore, In a Phase 3 trial called PINETREE, Veklury reduced the risk of COVID-19-related hospitalization or all-cause death by 87% compared to placebo in high-risk non-hospitalized patients. Moreover, Gilead administers a three-day course of Veklury to patients who are not in the hospital. For hospitalized patients, the typical treatment duration is 5 days, but this can be extended to 10 days. The new approval allows Veklury to be used in outpatient settings such as skilled nursing facilities, home health care, and infusion centers.

AbbVie’s Skyrizi Received its Second Psoriatic Arthritis Nod, Following Rinvoq

The FDA has approved Skyrizi for Psoriatic Arthritis (PsA) treatment in adults, following the approval of Rinvoq in December. Skyrizi is also approved for the treatment of adults with who are not suitable for systemic therapy or phototherapy.

The PsA approval was based on the results of two randomized, double-blind, placebo-controlled, Phase 3 studies, KEEPsAKE-1 and KEEPsAKE-2, which compared the efficacy and safety of risankizumab, an interleukin-23 antagonist, to placebo in adults with active PsA. The proportion of patients who obtained an American College of Rheumatology (ACR) 20 response at week 24 was the primary outcome in both studies. At the six-month mark, 57.3% of Skyrizi patients in Keepsake-1 and 51.3% of individuals on the AbbVie medicine in Keepsake-2 experienced at least a 20% improvement in their symptoms. In Keepsake-1 and KEEPsAKE-2, only 33.5% and 26.5% of placebo participants met the primary endpoint, respectively. Skyrizi also outperformed placebo at improving skin lesions in patients with coexisting plaque psoriasis, as evaluated by the Psoriasis Area Severity Index (PASI 90) at the 6-month mark. Furthermore, Skyrizi also helped patients with dactylitis and enthesitis minimize swelling of their fingers and toes, as well as swelling of the enthesis (where a tendon or ligament meets a person’s bone). 

The Skyrizi regimen used in the new indication is the same as that used in moderate-to-severe Plaque Psoriasis. After two beginning doses, a patient receives a single 150 mg injection beneath the skin four times a year. Skyrizi can be used alone or in combination with disease-modifying antirheumatic medications to treat Rheumatoid Arthritis.

Polpharma Looking For a Joint Bidder in a Potential $4 Billion Buyout of Zentiva

In the latest commercial update from the European pharmaceutical market, Poland’s largest drug maker Polpharma is set to acquire Czech rival Zentiva. Polpharma is looking forward to a joint investor for a possible $4 billion takeover. As per various reports, currently, the bidding process is in the early stage, and what will be the overall structure of the deal will be clear in the coming time.

Zentiva was once Sanofi’s generic drug department and is currently operating in over 40+ countries, including the Czech Republic, India, and Romania. Polpharma is the leading generic drugs player in the Polish pharmaceutical market with over 780 products. The company has a strong presence in Poland, Kazakhstan, and Russia with 8 manufacturing plants and 7 research and development centers. 
The Zentiva takeover bid is expected to touch the €3.5 billion ($4 billion) mark, which is much higher than what Advent International paid to French pharmaceutical giant Sanofi for the acquisition in 2018. Last year, Advent rejected proposals for an initial public offering of the Zentiva last year.