Pipeline News and Updates
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Regulatory Update
The FDA approved for lemborexant (Dayvigo, Eisai) on 12/23/19 for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance. The FDA approved for lumateperone (Caplyta, Intra-Cellular Therapies) on 12/23/19 for the treatment of schizophrenia in adults. Lumateperone has a boxed warning due to an increased risk of death for elderly patients with dementia-related psychosis. The label also contains a warning for increased risk for cerebrovascular events in this population. The FDA approved ubrogepant (Ubrelvy, Allergan) on 12/23/19 for the acute treatment of migraine with or without aura in adults. Announced Research Updates Shanghai Green Valley Pharmaceutical plans to initiate an 18-month, 2,046 patient, Phase III trial in the U.S. and Europe in 2020 that will evaluate oligomannate in the treatment of mild-to-moderate Alzheimer's disease. Results were announced in the fall of 2019 from a 9-month trial, which found oligomannate slowed the decrease in the ADAS-Cog12 Score compared to placebo. While researchers were skeptical due to the short duration of the trial and lack of details, the results led to conditional approval in China. The new trial is being undertaken to answer questions about the drug from the FDA and EMA. Published Research Updates In a 312 patient, Phase III trial, pixantrone/rituximab did not improve progression free survival compared to gemcitabine/rituximab in patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) grade 3 who relapsed after ≥1 rituximab-containing regimen and were not eligible for a stem cell transplant. The World Health Organization recommended fexinidazole as a first-line treatment option for human African trypanosomiasis. The Committee for Human Medicinal Products (CHMP) of the European Medicines Agency (EMA) recommended approval of fexinidazole for the treatment of human African trypanosomiasis (HAT), more commonly known as sleeping sickness. CHMP gave the opinion under Article 58, which is designed to provide guidance for drugs that are intended for use in countries outside the European Union. Fexinidazole was approved for use in the Democratic Republic of the Congo. Regulatory Update
The FDA approved trastuzumab deruxtecan (Enhertu, AstraZeneca/Daiichi Sankyo) on 12/19/19, for the treatment of unresectable or metastatic HER2-positive breast cancer that has received two or more prior anti-HER2-based regimens in the metastatic setting. The FDA approved Merck’s Ebola virus vaccine (Ervebo) on 12/20/19, for the prevention of Ebola virus disease caused by the Zaire ebola virus in people at least 18 years old. The FDA approved enfortumab vedotin (Padcev, Astellas/Seattle Genetics) on 12/18/19 for the treatment of locally advanced or metastatic urothelial cancer that has progressed on chemotherapy and immunotherapy. The FDA rejected ViiV Healthcare/Janssen’s NDA for the combination of cabotegravir and rilpivirine for HIV treatment, due to manufacturing issues. The FDA’s review of tazemetostat found a lack of efficacy compared to standard therapies and the potential for secondary malignancies that short trial durations may not have fully described. But the FDA’s Oncologic Drugs Advisory Committee voted 11-0 with two abstentions to recommend approval of tazemetostat for the treatment of metastatic or inoperable locally advanced epithelioid sarcoma, due to the low response rate with currently approved treatments. Deciphera filed an NDA for ripretinib for the treatment of gastrointestinal stromal tumors. The FDA designated Orphazyme’s arimoclomol a Fast Track drug for the treatment of sporadic Inclusion Body Myositis. PharmaMar submitted an NDA for lurbinectedin for the treatment of small cell lung cancer. The FDA designated Cascadian Therapeutics’ tucatinib a Breakthrough Therapy when given in combination with trastuzumab and capecitabine, for the treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer. BMS filed a BLA for lisocabtagene maraleucel for the treatment of relapsed or refractory large B-cell lymphoma (LBCL) after at least two prior therapies. MacroGenics filed a BLA for margetuximab for the treatment of patients with metastatic HER2-positive breast cancer in combination with chemotherapy. Gilead submitted an NDA for filgotinib for the treatment of moderate-to-severe rheumatoid arthritis. Announced Research Updates
Regulatory Update
The FDA approved golodirsen (Vyondys 53, Sarepta Therapeutics) on 12/12/2019 for the treatment of Duchenne muscular dystrophy amenable to exon 53 skipping. We took a look at this surprise reversal of the August 2019 rejection of the drug in a post last week. The FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee voted 12-0 to recommend approval of Horizon Therapeutics’ teprotumumab in December 2019 for the treatment of Thyroid Eye Disease. The FDA lifted the clinical trial hold for Abeona Therapeutics’ EB-101 targeting recessive dystrophic epidermolysis bullosa The FDA designated Dermira/Roche’s lebrikizumab a Fast Track treatment for moderate-to-severe atopic dermatitis. The FDA Cardiovascular and Renal Drugs Advisory Committee voted 11-2 against recommending approval of Correvio’s vernakalant due to safety concerns over hypotension, arrhythmias, and conduction disturbance. Biocryst submitted an NDA for BCX7353 in December 2019 with a hereditary angioedema indication. Seattle Genetics plans to file an NDA and MAA for tucatinib in 1Q20. Announced Research Updates
The FDA approved golodirsen (Vyondys 53, Sarepta Therapeutics) on 12/12/2019 for the treatment of Duchenne muscular dystrophy amenable to exon 53 skipping. This is a reversal of the August 2019 decision, where the FDA rejected golodirsen due to the risk of infection with intravenous infusion ports and renal toxicity seen in pre-clinical studies.
Sarepta plans to price golodirsen similar to eteplirsen. The average annual patient cost for eteplirsen is $300,000, but the cost can exceed $1 million because the drug is dosed by weight. A review by ICER of treatments for Duchenne’s found insufficient data that a slight increase in levels of dystrophin with eteplirsen and golodirsen provides a clinically significant effect. Due to the lack of evidence supporting a clinical benefit with the drugs, ICER did not estimate the pharmacoeconomic impact of either drug. Sarepta has shown that golodirsen will increase dystrophin levels, but has not completed studies to demonstrate an improvement in muscle function. The FDA is requiring Sarepta to complete a clinical efficacy study, so the company is recruiting at least 45 boys for the Phase III ESSENCE trial that will compare golodirsen to placebo on the impact of a 6-minute walking test. The trial is projected to be completed in 2024. Regulatory Update
The FDA rejected Lexicon Pharmaceuticals/Sanofi’s sotagliflozin a second time as a treatment for type 1 diabetes on 12/2/2019. Previously, the FDA's Endocrinologic and Metabolic Drugs Advisory Committee had a split decision (8-8) on sotagliflozin on whether to recommend approval of the drug as an add-on to insulin therapy in patients with type 1 diabetes in January 2019. Some members of the committee expressed concern regarding the increased risk for diabetic ketoacidosis with the drug. The FDA rejected sotagliflozin as a treatment for type 1 diabetes on 3/22/2019. The EMA approved sotagliflozin in April 2019 for the treatment of Type 1 Diabetes. Sanofi ceased participation in the development of sotagliflozin in July 2019 after the results from 3 Phase III type 2 diabetes trials were announced. The FDA rejected RVT-802 on 12/5/19 due to manufacturing issues. Immunomedics resubmitted the BLA for sacituzumab govitecan for the treatment of resistant metastatic triple-negative breast cancer. ViiV Healthcare submitted an NDA for fostemsavir in December 2019. Fostemsavir was bought from BMS in December 2015. The FDA has placed a partial clinical hold on four of Clementia’s palovarotene trials [(two fibrodysplasia ossificans progressiva (FOP) studies and two osteochondroma studies)] due to reports of early growth plate closure in patients with FOP in patients under the age of 14. Announced Research Updates
During October and November 2019, we saw the FDA approve thirteen new investigational drugs. Five of these drugs have annual costs in excess of $100,000. Each of these potential budget busters was approved months ahead of their PDUFA Dates, targeting such indications as the most common cystic fibrosis mutation, mantle cell lymphoma for patients who have received at least one prior therapy, sickle cell disease, partial-onset seizures in adults, and complicated urinary tract infections.
Here’s a link to a relevant article about the five budget busters from the November 27th ENDPOINTS News about approval process, Congress’ viewpoint and what FDA is analyzing https://endpts.com/fda-approves-5-new-costly-drugs-well-ahead-of-pdufa-dates/ Thirteen October and November Approvals
ICER’s Review of Migraine Medications ICER released a draft review of lasmiditan, ubrogepant and rimegepant in November 2019. ICER found the drugs to be comparable to each other in efficacy, but not as efficacious as triptans. Lasmiditan, ubrogepant and rimegepant would provide a benefit for patients with cardiovascular disease that have a contraindication to triptans, were not helped by triptans or do not tolerate them. Since triptans are available as generics, ICER concludes that triptans would provide a greater benefit at a lower cost than lasmiditan, ubrogepant or rimegepant. To reach a threshold of $150,000 per quality-adjusted life year ICER estimated an annual cost of $1,850 for lasmiditan, $1,780 for rimegepant and $1,740 for ubrogepant. Regulatory Update
The FDA approved voxelotor (Oxbryta, Global Blood Therapeutics) on 11/25/2019 for the treatment of sickle cell disease in patients 12 years and older. The drug had a PDUFA Date of 2/26/2020 and the FDA gave voxelotor Orphan Drug, Fast Track and Breakthrough Therapy Priority Designations. The FDA granted a priority review for risdiplam (RG7916) targeting spinal muscular atrophy and set a PDUFA date for 5/24/2020. It is the only drug in our knowledge base targeting spinal muscular atrophy. The FDA assigned pemigatinib a Priority Review for the treatment of locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements and assigned a PDUFA date of 5/30/2020. CymaBay has terminated clinical trials evaluating seladelpar as a treatment for non-alcoholic steatohepatitis (NASH) and primary sclerosing cholangitis (PSC) and put primary biliary cholangitis (PBC) studies on hold while it investigates atypical liver histological findings. There are eleven other investigational drugs in the Pharmaceutical Pipeline Tracker targeting NASH. Announced Research Updates ChemoCentryx announced that in the 52-week, 331 patient, Phase III, ADVOCATE trial, 72.3% of patients treated with avacopan achieved remission [Birmingham Vasculitis Activity Score of zero and no glucocorticoid treatment for anti-neutrophil cytoplasmic antibody-associated (ANCA) vasculitis for at least the preceding four weeks] at 26 weeks compared to 70.1% with corticosteroids. Additionally, 65.7% of avacopan patients remained in remission at 52 weeks compared to 54.9% with glucocorticoids. Published Research Updates In a 141 patient, Phase IIb, open-label trial, eryaspase plus either gemcitabine or FOLFOX treated patients had an overall survival (OS) of 6.2 months compared to 4.9 months with standard chemotherapy and progression-free survival (PFS) of 2 months compared to 1.8 months in patients with advanced pancreatic adenocarcinoma with low asparagine synthetase (ASNS) expression. In the overall population OS was 6 months compared to 4.4 months and PFS was 2 months compared to 1.6 months. AstraZeneca/Lilly’s lanabecestat 104-week, 2,218 patient, Phase II/III, AMARANTH trial and the 78-week, 1,722 patient, Phase III DAYBREAK-ALZ trial were both terminated early after an interim analysis failed to demonstrate an improvement or slowing in decline in the Alzheimer Disease Assessment Scale–cognitive subscale (ADAS-Cog13) compared to placebo in patients with early or mild Alzheimer’s disease. In the 107-week, Phase III SAkuraSky trial, of 83 patients with neuromyelitis optica spectrum disorder (NMOSD) that were receiving immunosuppressive therapy, 80% of patients treated with satralizumab were relapse free compared to 57% of those given placebo. In the 681 patient, Phase II/III PALM Trial, mortality was 33.5% after treatment with REGN-EB3, 35.1% after MAb114, 53.1% with remdesivir compared to 49.7% with porgaviximab (ZMapp) in patients infected with the Ebola virus. |
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